Multiple sclerosis and optic nerve: an analysis of retinal nerve fiber layer thickness and color Doppler imaging parameters

PubMed Central

Akçam, H T; Capraz, I Y; Aktas, Z; Batur Caglayan, H Z; Ozhan Oktar, S; Hasanreisoglu, M; Irkec, C

2014-01-01

Purpose To compare both retinal nerve fiber layer thickness and orbital color Doppler ultrasonography parameters in patients with multiple sclerosis (MS) versus healthy controls. Methods This is an observational case–control study. Forty eyes from MS patients and twenty eyes from healthy volunteers were examined. Eyes were classified into three groups as group 1, eyes from MS patients with previous optic neuritis (n=20); group 2, eyes from MS patients without previous optic neuritis (n=20); and group 3, eyes from healthy controls (n=20). Following complete ophthalmologic examination and retinal nerve fiber layer thickness measurement for each group, blood flow velocities of posterior ciliary arteries, central retinal artery, ophthalmic artery, and superior ophthalmic vein were measured. Pourcelot index (resistive index), an indicator of peripheral vascular resistance, was also calculated. The statistical assessment was performed with the assistance of Pearson's Chi-square test, Mann–Whitney U-test, Kruskal–Wallis test, and Spearman's correlation test. Results The studied eyes exposed similar values in terms of intraocular pressure and central corneal thickness, implying no evidence in favor of glaucoma. All nerve fiber layer thickness values, except superior nasal quadrants, in group 1 were found to be significantly thinner than groups 2 and 3. Blood flow velocity and mean resistivity index parameters were similar in all the groups. Conclusions In MS patients, especially with previous optic neuritis, diminished retinal nerve fiber layer thickness was observed. Contrary to several studies in the current literature, no evidence supporting potential vascular origin of ocular involvement in MS was found. PMID:25081285

Immunohistochemical demonstration of enkephalin-containing nerve fibers in guinea pig and rat lungs.

PubMed

Shimosegawa, T; Foda, H D; Said, S I

1989-08-01

Met-enkephalin (Met-Enk) and Leu-enkephalin (Leu-Enk), the opioid peptides originally isolated from the brain, are believed to act as inhibitory neuromodulators at various synaptic sites. In this immunohistochemical study, we have investigated the localization and distribution of Met- and Leu-Enk immunoreactivities in airways and pulmonary vessels of guinea pigs and rats. Immunoreactivities to both peptides were found in nerve fibers and nerve terminals distributed mainly to the trachea and major bronchi, and were especially prevalent in the smooth muscle layer, in the lamina propria, and around tracheal and bronchial glands, but not in the epithelium. Few immunoreactive nerve fibers were detected in smaller bronchi, bronchioles, and alveoli. Enkephalin-immunoreactive nerve fibers were also localized in the walls of pulmonary and bronchial vessels. Within airway microganglia, immunoreactivity was observed in a few nerve terminals, but not in ganglion cell bodies. Met- and Leu-Enk immunoreactive nerve fibers showed similar distribution patterns, though minor differences were noted between the two species: Enk-immunoreactive nerve fibers in the smooth muscle layer were more abundant in guinea pigs than in rats, whereas those in mucous glands were richer in rats than in guinea pigs. These results document the presence of Met- and Leu-Enk immunoreactivity in nerve fibers supplying guinea pig and rat airways and pulmonary vessels, and provide a morphologic basis for the view that enkephalins are likely neurotransmitters or neuromodulators in the lung.

Variations in retinal nerve fiber layer measurements on optical coherence tomography after implantation of trifocal intraocular lens.

PubMed

García-Bella, Javier; Martínez de la Casa, José M; Talavero González, Paula; Fernández-Vigo, José I; Valcarce Rial, Laura; García-Feijóo, Julián

2018-01-01

To establish the changes produced after implantation of a trifocal intraocular lens (IOL) on retinal nerve fiber layer measurements performed with Fourier-domain optical coherence tomography (OCT). This prospective study included 100 eyes of 50 patients with bilateral cataract in surgical range, no other associated ocular involvement, refractive errors between +5 and -5 spherical diopters, and less than 1.5 D of corneal astigmatism. The eyes were operated by phacoemulsification with implantation of 2 different trifocal IOLs (FineVision and AT LISA tri 839MP) in randomized equal groups. Cirrus OCT and Spectralis OCT were performed before surgery and 3 months later. Both analyzed the thickness of the nerve fiber layer and thickness divided by quadrants (6 in case of Spectralis and 4 in case of Cirrus HD). The mean age of patients was 67.5 ± 5.8 years. The global nerve fiber layer thickness measured with Spectralis OCT was 96.77 μm before surgery and 99.55 μm after. With Cirrus OCT, the global thickness was 85.29 μm before surgery and 89.77 μm after. Statistically significant differences in global thickness measurements between preimplantation and postimplantation of the IOL were found with both OCT in the 2 groups. Statistically significant differences were also found in temporal and superior quadrants. The implantation of a diffractive trifocal IOL alters the results of the optic nerve fiber layer on Fourier-domain OCT in these patients, which should be taken into account in the posterior study of these patients.

Optical coherence tomography detects characteristic retinal nerve fiber layer thickness corresponding to band atrophy of the optic discs.

PubMed

Kanamori, Akiyasu; Nakamura, Makoto; Matsui, Noriko; Nagai, Azusa; Nakanishi, Yoriko; Kusuhara, Sentaro; Yamada, Yuko; Negi, Akira

2004-12-01

To analyze retinal nerve fiber layer (RNFL) thickness in eyes with band atrophy by use of optical coherence tomography (OCT) and to evaluate the ability of OCT to detect this characteristic pattern of RNFL loss. Cross-sectional, retrospective study. Thirty-four eyes of 18 patients with bitemporal hemianopia caused by optic chiasm compression by chiasmal tumors were studied. All eyes were divided into 3 groups according to visual field loss grading after Goldmann perimetry. Retinal nerve fiber layer thickness measurements with OCT. Retinal nerve fiber layer thickness around the optic disc was measured by OCT (3.4-mm diameter circle). Calculation of the changes in OCT parameters, including the horizontal (nasal + temporal quadrant RNFL thickness) and vertical values (superior + inferior quadrant RNFL thickness) was based on data from 160 normal eyes. Comparison between the 3 visual field grading groups was done with the analysis of variance test. The receiver operating characteristic (ROC) curve for the horizontal and vertical value were calculated, and the areas under the curve (AUC) were compared. Retinal nerve fiber layer thickness in eyes with band atrophy decreased in all OCT parameters. The reduction rate in average and temporal RNFL thickness and horizontal value was correlated with visual field grading. The AUC of horizontal value was 0.970+/-0.011, which was significantly different from AUC of vertical value (0.903+/-0.022). The degree of RNFL thickness reduction correlated with that of visual field defects. Optical coherence tomography was able to identify the characteristic pattern of RNFL loss in these eyes.

Reduction in Retinal Nerve Fiber Layer Thickness in Young Adults with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Emberti Gialloreti, Leonardo; Pardini, Matteo; Benassi, Francesca; Marciano, Sara; Amore, Mario; Mutolo, Maria Giulia; Porfirio, Maria Cristina; Curatolo, Paolo

2014-01-01

Recent years have seen an increase in the use of retinal nerve fiber layer (RNFL) evaluation as an easy-to-use, reproducible, proxy-measure of brain structural abnormalities. Here, we evaluated RNFL thickness in a group of subjects with high functioning autism (HFA) or with Asperger Syndrome (AS) to its potential as a tool to study autism…

Normative values for optical coherence tomography parameters in healthy children and interexaminer agreement for choroidal thickness measurements.

PubMed

Turan, Kadriye Erkan; Sekeroglu, Hande Taylan; Baytaroglu, Ata; Bezci, Figen; Karahan, Sevilay

2018-01-01

To (a) determine the normative values for optical coherence tomography (OCT) parameters such as central macular thickness, retinal nerve fiber layer thickness, and choroidal thickness in healthy children; (b) investigate the relationships of these parameters with axial length, central corneal thickness, refractive errors, and intraocular pressure; and (c) determine interexaminer agreement for choroidal thickness measurements. In this cross-sectional study, 120 healthy children aged 8-15 years underwent detailed ophthalmological examination and OCT measurements. Choroidal thickness was measured at three separate locations by two independent examiners. The mean global retinal nerve fiber layer thickness was 98.75 ± 9.45 μm (79.0-121.0). The mean central macular thickness was 232.29 ± 29.37 μm (190.0-376.0). The mean subfoveal choroidal thickness obtained by examiner 1 was 344.38 ± 68.83 μm and that obtained by examiner 2 was 344.04 ± 68.92 μm. Interexaminer agreement was between 99.6%-99.8% for choroidal thickness at three separate locations. Central macular thickness increased with axial length (r=0.245, p=0.007). Choroidal thickness increased with age (r=0.291, p=0.001) and decreased with axial length (r=-0.191, p=0.037). Global retinal nerve fiber layer thickness decreased with axial length (r=-0.247, p=0.007) and increased with central corneal thickness (r=0.208, p=0.022). Global retinal nerve fiber layer thickness positively correlated with choroidal thickness (r=0.354, p<0.001). Global retinal nerve fiber layer thickness (r=0.223, p=0.014) and choroidal thickness (r=0.272, p=0.003) increased with the spherical equivalent (D). Optical coherence tomography parameters showed a wide range of variability in children. Retinal nerve fiber layer thickness, central macular thickness, and choroidal thickness were found to be either inter-related or correlated with age, central corneal thickness, axial length, and refractive errors. Furthermore, manual measurements of choroidal thickness showed high interexaminer agreement. Because normative values for optical coherence tomography parameters differed in children, the measurements should be interpreted according to an age-appropriate database.

Regeneration of junctional epithelium and its innervation in adult rats: a study using immunocytochemistry for p75 nerve growth factor receptor and calcitonin gene-related peptide.

PubMed

Redd, P E; Byers, M R

1994-05-01

Junctional epithelium (JE) is a rapidly proliferating tissue that connects the gum to the tooth, that provides a free surface for bidirectional movement of substances between the body and the oral cavity, and that participates in defense against bacterial infection. It is innervated by numerous sensory nerve fibers that are immunoreactive (IR) for neuropeptides such as calcitonin gene-related peptide (CGRP), and for low affinity nerve growth factor receptor (p75-NGFR). Basal epithelial cells of the JE and of adjacent sulcular epithelium also have intense p75-NGFR-IR. In the present study we removed a wedge of the free gingiva and JE from the anterior side of the maxillary first molar of adult rats, and then studied the return of nerve fibers during tissue regeneration from 1-63 days after gingivectomy. The nerve fibers entered the adjacent healing sulcular epithelium before innervating the new JE, in both cases prior to return of epithelial cell p75-NGFR-IR. The regenerating nerve fibers completely bypassed the zone of epithelial down-growth (long junctional epithelium, LJE) that was briefly present along the tooth from 1-3 weeks after injury. The LJE did not have p75-NGFR-IR and was gradually replaced by a modified thicker regenerated junctional epithelium (RJE). The RJE was attached along the injured root surface, had numerous nerves in basal layers, and it had begun to regain p75-NGFR-IR staining of basal epithelial cells by 22 d. Regenerating nerve fibers at 6-10 d had unusually weak CGRP-IR and greatly increased p75-NGFR-IR. Both nerve stains had returned to normal by 3-6 weeks. The intense p75-NGFR-IR of regenerating nerves was found on both axonal and Schwann cell membranes using electron microscopic immunocytochemistry. In both the normal and regenerating JE, nerve fibers were rare in the attachment layers next to the anterior side of the maxillary first molar, compared to well-innervated basal layers. The complete avoidance of LJE by regenerating nerve fibers and its lack of p75-NGFR-IR suggest that its functions do not require innervation and that it does not make neurotrophic growth factors.

INCOMPLETE REPAIR OF RETINAL STRUCTURE AFTER VITRECTOMY WITH INTERNAL LIMITING MEMBRANE PEELING.

PubMed

Hisatomi, Toshio; Tachibana, Takashi; Notomi, Shoji; Nakatake, Shunji; Fujiwara, Kohta; Murakami, Yusuke; Ikeda, Yasuhiro; Yoshida, Shigeo; Enaida, Hiroshi; Murata, Toshinori; Sakamoto, Taiji; Sonoda, Koh-Hei; Ishibashi, Tatsuro

2017-08-01

To examine retinal changes after vitrectomy with internal limiting membrane (ILM) peeling, we used a cynomolgus monkey model and focused on surgical damages of ILM peeling for long observational period of 3 years. Vitrectomy was performed followed by ILM peeling similar to clinical settings in humans. Ultrastructural changes of the retina were investigated by light, transmission, and scanning electron microscopy at 3 months and 3 years after ILM peeling. Ultrastructural study showed that the ILM peeled area was still clearly recognized after 3 years. The Müller cell processes covered most of the retina; however, the nerve fiber layer was partly uncovered and exposed to the vitreous space. The arcuate linear nerve fiber bundles were observed as comparable with dissociated optic nerve fiber layer appearance. Small round retinal surface defects were also observed around macula, resembling the dimple sign. Forceps-related retinal thinning was also found on the edge of ILM peeling, where we started peeling with fine forceps. The ultrastructural studies showed that most of ILM peeling area was covered with glial cells during wound healing processes. Retinal changes were found comparable with dissociated optic nerve fiber layer appearance or dimple sign, which were clinically observed with optical coherence tomography.

Nerve fiber layer (NFL) degeneration associated with acute q-switched laser exposure in the nonhuman primate

NASA Astrophysics Data System (ADS)

Zwick, Harry; Zuclich, Joseph A.; Stuck, Bruce E.; Gagliano, Donald A.; Lund, David J.; Glickman, Randolph D.

1995-01-01

We have evaluated acute laser retinal exposure in non-human primates using a Rodenstock scanning laser ophthalmoscope (SLO) equipped with spectral imaging laser sources at 488, 514, 633, and 780 nm. Confocal spectral imaging at each laser wavelength allowed evaluation of the image plane from deep within the retinal vascular layer to the more superficial nerve fiber layer in the presence and absence of the short wavelength absorption of the macular pigment. SLO angiography included both fluorescein and indocyanine green procedures to assess the extent of damage to the sensory retina, the retinal pigment epithelium (RPE), and the choroidal vasculature. All laser exposures in this experiment were from a Q-switched Neodymium laser source at an exposure level sufficient to produce vitreous hemorrhage. Confocal imaging of the nerve fiber layer revealed discrete optic nerve sector defects between the lesion site and the macula (retrograde degeneration) as well as between the lesion site and the optic disk (Wallerian degeneration). In multiple hemorrhagic exposures, lesions placed progressively distant from the macula or overlapping the macula formed bridging scars visible at deep retinal levels. Angiography revealed blood flow disturbance at the retina as well as at the choroidal vascular level. These data suggest that acute parafoveal laser retinal injury can involve both direct full thickness damage to the sensory and non-sensory retina and remote nerve fiber degeneration. Such injury has serious functional implications for both central and peripheral visual function.

Ocular toxocariasis presenting as bilateral scleritis with suspect retinal granuloma in the nerve fiber layer: a case report.

PubMed

Pak, Kang Yeun; Park, Sung Who; Byon, Ik Soo; Lee, Ji Eun

2016-08-18

This report details ocular toxocariasis presenting as bilateral scleritis with suspect retinal granuloma in the nerve fiber layer. The patient presented with scleritis, which did not improve with systemic steroid. Intraocular pressure was elevated, and well demarcated hyper-reflective round lesion were noted in both eyes. He had a history of general ache and concurrent onset of ocular symptoms the day after eating raw meat. Systemic work-ups revealed no remarkable abnormalities except antibody for toxocara. Oral albendazole and steroid were prescribed. The inflammation and swellings resolved without recurrence. In the current case, scleritis with suspect granuloma in the nerve fiber layer seems to be caused by toxocara. Ocular toxocariasis can be presented as atypical features. Serologic exams for toxocariasis would be considered not only in typical features but also in other uveitis or scleritis, particularly when the patient has a related history.

Registration of adaptive optics corrected retinal nerve fiber layer (RNFL) images

PubMed Central

Ramaswamy, Gomathy; Lombardo, Marco; Devaney, Nicholas

2014-01-01

Glaucoma is the leading cause of preventable blindness in the western world. Investigation of high-resolution retinal nerve fiber layer (RNFL) images in patients may lead to new indicators of its onset. Adaptive optics (AO) can provide diffraction-limited images of the retina, providing new opportunities for earlier detection of neuroretinal pathologies. However, precise processing is required to correct for three effects in sequences of AO-assisted, flood-illumination images: uneven illumination, residual image motion and image rotation. This processing can be challenging for images of the RNFL due to their low contrast and lack of clearly noticeable features. Here we develop specific processing techniques and show that their application leads to improved image quality on the nerve fiber bundles. This in turn improves the reliability of measures of fiber texture such as the correlation of Gray-Level Co-occurrence Matrix (GLCM). PMID:24940551

Rod-Shaped Neural Units for Aligned 3D Neural Network Connection.

PubMed

Kato-Negishi, Midori; Onoe, Hiroaki; Ito, Akane; Takeuchi, Shoji

2017-08-01

This paper proposes neural tissue units with aligned nerve fibers (called rod-shaped neural units) that connect neural networks with aligned neurons. To make the proposed units, 3D fiber-shaped neural tissues covered with a calcium alginate hydrogel layer are prepared with a microfluidic system and are cut in an accurate and reproducible manner. These units have aligned nerve fibers inside the hydrogel layer and connectable points on both ends. By connecting the units with a poly(dimethylsiloxane) guide, 3D neural tissues can be constructed and maintained for more than two weeks of culture. In addition, neural networks can be formed between the different neural units via synaptic connections. Experimental results indicate that the proposed rod-shaped neural units are effective tools for the construction of spatially complex connections with aligned nerve fibers in vitro. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Registration of adaptive optics corrected retinal nerve fiber layer (RNFL) images.

PubMed

Ramaswamy, Gomathy; Lombardo, Marco; Devaney, Nicholas

2014-06-01

Glaucoma is the leading cause of preventable blindness in the western world. Investigation of high-resolution retinal nerve fiber layer (RNFL) images in patients may lead to new indicators of its onset. Adaptive optics (AO) can provide diffraction-limited images of the retina, providing new opportunities for earlier detection of neuroretinal pathologies. However, precise processing is required to correct for three effects in sequences of AO-assisted, flood-illumination images: uneven illumination, residual image motion and image rotation. This processing can be challenging for images of the RNFL due to their low contrast and lack of clearly noticeable features. Here we develop specific processing techniques and show that their application leads to improved image quality on the nerve fiber bundles. This in turn improves the reliability of measures of fiber texture such as the correlation of Gray-Level Co-occurrence Matrix (GLCM).

EFFECT OF INTRAVITREAL RANIBIZUMAB ON GANGLION CELL COMPLEX AND PERIPAPILLARY RETINAL NERVE FIBER LAYER IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION USING SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY.

PubMed

Zucchiatti, Ilaria; Cicinelli, Maria V; Parodi, Maurizio Battaglia; Pierro, Luisa; Gagliardi, Marco; Accardo, Agostino; Bandello, Francesco

2017-07-01

To analyze the changes in ganglion cell complex and peripapillary retinal nerve fiber layer thickness, in central macular thickness and choroidal thickness on spectral domain optical coherence tomography in patients with neovascular age-related macular degeneration treated with intravitreal ranibizumab injections. All consecutive patients with untreated neovascular age-related macular degeneration received loading phase of three monthly intravitreal ranibizumab, followed by retreatments on a pro re nata protocol for 12 months. changes in ganglion cell complex and retinal nerve fiber layer at the end of follow-up. Secondary outcome: changes in best-corrected visual acuity, central macular thickness, and choroidal thickness at the end of follow-up. Choroidal thickness was measured at 500 μm, 1000 μm, and 1,500 μm intervals nasally, temporally, superiorly, and inferiorly to the fovea, respectively, on horizontal and vertical line scans centered on the fovea. Twenty-four eyes were included. Ganglion cell complex and peripapillary retinal nerve fiber layer thickness did not show statistically significant changes through 12 months (55.6 ± 18.5 and 81.9 ± 9.9 μm at baseline, 52.7 ± 19.3 and 84.6 ± 15.5 μm at month 12, P > 0.05). Central macular thickness showed progressive decrease from baseline to month 12, with maximum reduction at month 3 (P < 0.001). Statistically significant reduction in choroidal thickness was registered in the nasal 500, 1000, and 1,500 μm from the fovea, corresponding to the papillomacular region (from 169.6 ± 45.3 to 153.9 ± 46.9, P < 0.001). Intravitreal ranibizumab injections did not affect retinal nerve fiber layer and ganglion cell complex thickness in 1-year follow-up. Choroidal thickness in papillomacular area and central macular thickness was significantly reduced at the end of treatment. Further studies, with larger sample, longer follow-up, and greater number of injections, are warranted.

[Clinical evaluation of the optic disc in glaucoma].

PubMed

Greslechner, R; Spiegel, D

2016-10-01

Glaucoma is defined as a progressive neuropathy of the optic nerve, characterized by specific changes of the optic disc, parapapillary region, and retinal nerve fiber layer. Characteristic glaucomatous changes of the optic disc, parapapillary region, and retinal nerve fiber layer are discussed and their ophthalmoscopic examination is described. A literature search in the PubMed database was conducted. A systematic step-by-step approach to a qualitative and quantitative ophthalmoscopic evaluation of the optic disc regarding glaucomatous damage is presented. A systematic, clinical, qualitative, and quantitative assessment of the optic disc can be performed with little effort and forms the basis for diagnosis and treatment of glaucoma.

Design of barrier coatings on kink-resistant peripheral nerve conduits

PubMed Central

Clements, Basak Acan; Bushman, Jared; Murthy, N Sanjeeva; Ezra, Mindy; Pastore, Christopher M; Kohn, Joachim

2016-01-01

Here, we report on the design of braided peripheral nerve conduits with barrier coatings. Braiding of extruded polymer fibers generates nerve conduits with excellent mechanical properties, high flexibility, and significant kink-resistance. However, braiding also results in variable levels of porosity in the conduit wall, which can lead to the infiltration of fibrous tissue into the interior of the conduit. This problem can be controlled by the application of secondary barrier coatings. Using a critical size defect in a rat sciatic nerve model, the importance of controlling the porosity of the nerve conduit walls was explored. Braided conduits without barrier coatings allowed cellular infiltration that limited nerve recovery. Several types of secondary barrier coatings were tested in animal studies, including (1) electrospinning a layer of polymer fibers onto the surface of the conduit and (2) coating the conduit with a cross-linked hyaluronic acid-based hydrogel. Sixteen weeks after implantation, hyaluronic acid-coated conduits had higher axonal density, displayed higher muscle weight, and better electrophysiological signal recovery than uncoated conduits or conduits having an electrospun layer of polymer fibers. This study indicates that braiding is a promising method of fabrication to improve the mechanical properties of peripheral nerve conduits and demonstrates the need to control the porosity of the conduit wall to optimize functional nerve recovery. PMID:26977288

THICKNESS OF THE MACULA, RETINAL NERVE FIBER LAYER, AND GANGLION CELL-INNER PLEXIFORM LAYER IN THE AGE-RELATED MACULAR DEGENERATION: The Repeatability Study of Spectral Domain Optical Coherence Tomography.

PubMed

Shin, Il-Hwan; Lee, Woo-Hyuk; Lee, Jong-Joo; Jo, Young-Joon; Kim, Jung-Yeul

2018-02-01

To determine the repeatability of measuring the thickness of the central macula, retinal nerve fiber layer, and ganglion cell-inner plexiform layer (GC-IPL) using spectral domain optical coherence tomography (Cirrus HD-OCT) in eyes with age-related macular degeneration. One hundred and thirty-four eyes were included. The measurement repeatability was assessed by an experienced examiner who performed two consecutive measurements using a 512 × 128 macular cube scan and a 200 × 200 optic disk cube scan. To assess changes in macular morphology in patients with age-related macular degeneration, the patients were divided into the following three groups according to the central macular thickness (CMT): A group, CMT < 200 μm; B group, 200 μm ≤ CMT < 300 μm; and C group, CMT > 300 μm. Measurement repeatability was assessed using test-retest variability, a coefficient of variation, and an intraclass correlation coefficient. The mean measurement repeatability for the central macular, retinal nerve fiber layer, and GC-IPL thickness was high in the B group. The mean measurement repeatability for both the central macula and retinal nerve fiber layer thickness was high in the A and C groups, but was lower for the GC-IPL thickness. The measurement repeatability for GC-IPL thickness was high in the B group, but low in the A group and in the C group. The automated measurement repeatability for GC-IPL thickness was significantly lower in patients with age-related macular degeneration with out of normal CMT range. The effect of changes in macular morphology should be considered when analyzing GC-IPL thicknesses in a variety of ocular diseases.

Intraobserver reproducibility of retinal nerve fiber layer measurements using scanning laser polarimetry and optical coherence tomography in normal and ocular hypertensive subjects.

PubMed

Lleó-Pérez, A; Ortuño-Soto, A; Rahhal, M S; Martínez-Soriano, F; Sanchis-Gimeno, J A

2004-01-01

To evaluate quantitatively the intraobserver reproducibility of measurements of the retinal nerve fiber layer (RNFL) in healthy subjects and an ocular hypertensive population using two nerve fiber analyzers. Sixty eyes of normal (n=30) and ocular hypertensive subjects (n=30) were consecutively recruited for this study and underwent a complete ophthalmologic examination and achromatic automated perimetry. RNFL were measured using scanning laser polarimeter (GDx-VCC) and optical coherence tomography (OCT Model 3000). Reproducibility of the RNFL measurements obtained with both nerve fiber analyzers were compared using the coefficient of variation. In both groups the authors found fair correlations between the two methods in all ratio and thickness parameters. The mean coefficient of variation for measurement of the variables ranged from 2.24% to 13.12% for GDx-VCC, and from 5.01% to 9.24% for OCT Model 3000. The authors could not detect any significant differences between healthy and ocular hypertensive eyes, although in normal eyes the correlations improved slightly. Nevertheless, the test-retest correlation was slightly better for GDx-VCC than for OCT Model 3000 (5.55% and 7.11%, respectively). Retinal mapping software of both nerve fiber analyzers allows reproducible measurement of RNFL in both healthy subjects and ocular hypertensive eyes, and shows fair correlations and good intraobserver reproducibility. However, in our study, GDx showed a better test-retest correlation.

Fourier-domain optical coherence tomography and adaptive optics reveal nerve fiber layer loss and photoreceptor changes in a patient with optic nerve drusen.

PubMed

Choi, Stacey S; Zawadzki, Robert J; Greiner, Mark A; Werner, John S; Keltner, John L

2008-06-01

New technology allows more precise definition of structural alterations of all retinal layers although it has not been used previously in cases of optic disc drusen. Using Stratus and Fourier domain (FD) optical coherence tomography (OCT) and adaptive optics (AO) through a flood-illuminated fundus camera, we studied the retinas of a patient with long-standing optic disc drusen and acute visual loss at high altitude attributed to ischemic optic neuropathy. Stratus OCT and FD-OCT confirmed severe thinning of the retinal nerve fiber layer (RNFL). FD-OCT revealed disturbances in the photoreceptor layer heretofore not described in optic disc drusen patients. AO confirmed the FD-OCT findings in the photoreceptor layer and also showed reduced cone density at retinal locations associated with reduced visual sensitivity. Based on this study, changes occur not only in the RNFL but also in the photoreceptor layer in optic nerve drusen complicated by ischemic optic neuropathy. This is the first reported application of FD-OCT and the AO to this condition. Such new imaging technology may in the future allow monitoring of disease progression more precisely and accurately.

Distribution of TRPV1- and TRPV2-immunoreactive afferent nerve endings in rat trachea.

PubMed

Yamamoto, Yoshio; Sato, Yoshikazu; Taniguchi, Kazuyuki

2007-12-01

Nociception in the trachea is important for respiratory modulation. We investigated the distribution, neurochemical characteristics, and origin of nerve endings with immunoreactivity for candidate sensor channels, TRPV1 and TRPV2, in rat trachea. In the epithelial layer, the intraepithelial nerve endings and dense subepithelial network of nerve fibers were immunoreactive for TRPV1. In contrast, TRPV2 immunoreactivity was observed mainly in nerve fibers of the tracheal submucosal layer and in several intrinsic ganglion cells in the peritracheal plexus. Double immunostaining revealed that some TRPV1-immunoreactive nerve fibers were also immunoreactive for substance P or calcitonin gene-related peptide, but neither neuropeptide colocalized with TRPV2. Injection of the retrograde tracer, fast blue, into the tracheal wall near the thoracic inlet demonstrated labeled neurons in the jugular, nodose, and dorsal root ganglia at segmental levels of C2-C8. In the jugular and nodose ganglia, 59.3% (70/118) and 10.7% (17/159), respectively, of fast blue-labeled neurons were immunoreactive for TRPV1, compared to 8.8% (8/91) and 2.6% (5/191) for TRPV2-immunoreactive. Our results indicate that TRPV1-immunoreactive nerve endings are important for tracheal nociception, and the different expression patterns of TRPV1 and TRPV2 with neuropeptides may reflect different subpopulations of sensory neurons.

Scanning laser polarimetry retinal nerve fiber layer thickness measurements after LASIK.

PubMed

Zangwill, Linda M; Abunto, Teresa; Bowd, Christopher; Angeles, Raymund; Schanzlin, David J; Weinreb, Robert N

2005-02-01

To compare retinal nerve fiber layer (RNFL) thickness measurements before and after LASIK. Cohort study. Twenty participants undergoing LASIK and 14 normal controls. Retinal nerve fiber layer thickness was measured before LASIK and approximately 3 months after surgery in one eye each of 20 patients using a scanning laser polarimeter (GDx Nerve Fiber Analyzer) with fixed corneal compensation (FCC), one with variable corneal compensation (GDx VCC), and optical coherence tomography (OCT). Fourteen normal controls also were tested at baseline and approximately 3 months later. Retinal nerve fiber layer thicknesses measured with the GDx FCC, GDx VCC, and OCT. At baseline, mean (95% confidence interval [CI]) RNFL thicknesses for the GDx FCC, GDx VCC, and OCT were 78.1 microm (72.2-83.9), 54.3 microm (52.7-56.0), and 96.8 microm (93.2-100.5), respectively. In both LASIK and control groups, there were no significant changes between baseline and follow-up examinations in GDx VCC and OCT RNFL thickness measurements globally or in the superior and inferior quadrants (mean change, <5 microm for each instrument). In the control group, there also was no significant change in GDx FCC measurements between baseline and follow-up. In LASIK patients, significant reductions were observed in GDx FCC RNFL measurements. Average absolute values of the mean (95% CI) change in thickness were 12.4 microm (7.7-17.2), 15.3 microm (9.6-20.9), and 12.9 microm (7.6-18.1) for GDx FCC RNFL measurements superiorly, inferiorly, and globally, respectively (all Ps < or = 0.001). LASIK does not seem to change RNFL thickness. Reduction in GDx FCC RNFL thickness measurements after LASIK is a measurement artifact and is most likely due to erroneous compensation for corneal birefringence. With scanning laser polarimetry, it is mandatory to compensate individually for change in corneal birefringence after LASIK to ensure accurate RNFL assessment.

Optical Coherence Tomography in Glaucoma

NASA Astrophysics Data System (ADS)

Berisha, Fatmire; Hoffmann, Esther M.; Pfeiffer, Norbert

Retinal nerve fiber layer (RNFL) thinning and optic nerve head cupping are key diagnostic features of glaucomatous optic neuropathy. The higher resolution of the recently introduced SD-OCT offers enhanced visualization and improved segmentation of the retinal layers, providing a higher accuracy in identification of subtle changes of the optic disc and RNFL thinning associated with glaucoma.

[Pay attention on optical coherence tomography evaluation for optic nerve diseases].

PubMed

Wang, M

2016-12-11

Optical coherence tomography(OCT) had become the most important imaging technique in ophthalmology. OCT is able to segment the retinal nerve fiber layer and retinal ganglion cell layer accurately. Quantitative analysis can be performed for both layers. OCT is very important to evaluate the neuron and axon loss in optic nerve diseases diagnosis. Meanwhile, OCT has great value for differentiating glaucoma and macular diseases from optic nerve diseases. This review presented OCT application in optic nerve diseases diagnosis, differentiation diagnosis, the key points in use and the features of en face OCT and OCT angiography. It gave us suggestions that it should be pay more attention to OCT examination in diagnosis and treatment of optic nerve diseases. (Chin J Ophthalmol, 2016, 52: 885 - 888) .

Influence of myelinated retinal nerve fibers on retinal vessel density measurement with AngioVue OCT angiography.

PubMed

Holló, Gábor

2016-12-01

Myelinated retinal nerve fibers (MRNF) represent an asymptomatic developmental anomaly in which myelin sheaths extend to a group of retinal nerve fibers along their intraocular portion. The additional volume of the myelin sheaths causes displacement of the axons toward the vitreous body. We investigated the effect of localized MRNF on peripapillary vessel density measurement results using optical coherence tomography (OCT) angiography. Peripapillary angioflow density measurements (PAFD, % of the analyzed retinal area) were made with the AngioVue OCT (Optovue Inc., Fremont, USA). In both cases, the predominant position of MRNF was inferonasal to the disk. Vessel density was clearly greater in the area of the MRNF than in the surrounding retina in the optic nerve head (ONH) level, but it was lower than in the surrounding retina in the retinal nerve fiber layer (RNFL) level. In the ONH level, PAFD was higher in the MRNF area than in the spatially corresponding superonasal area (Case 1: 64.6 vs. 57.6 %; Case 2: 65.8 vs. 56.3 %). In contrast, in the RNFL level, PAFD was lower in the MRNF area than in the corresponding superonasal area (Case 1: 60.1 vs. 65.4 %; Case 2: 46.5 vs. 58.5 %). Our cases show that the effect of MRNF on OCT angiography vessel density is different in the different measurement layers. Clinicians may separate decreased vessel density caused by anterior RNFL displacement in MRNF areas from that caused by nerve fiber damage in optic neuropathies by evaluating PAFD in both the ONH and RNFL levels.

High aspect ratio template and method for producing same for central and peripheral nerve repair

NASA Technical Reports Server (NTRS)

Sakamoto, Jeff S. (Inventor); Chan, Christina (Inventor); Tuszynski, Mark Henry (Inventor); Mehrotra, Sumit (Inventor); Gros, Thomas (Inventor)

2011-01-01

Millimeter to nano-scale structures manufactured using a multi-component polymer fiber matrix are disclosed. The use of dissimilar polymers allows the selective dissolution of the polymers at various stages of the manufacturing process. In one application, biocompatible matrixes may be formed with long pore length and small pore size. The manufacturing process begins with a first polymer fiber arranged in a matrix formed by a second polymer fiber. End caps may be attached to provide structural support and the polymer fiber matrix selectively dissolved away leaving only the long polymer fibers. These may be exposed to another product, such as a biocompatible gel to form a biocompatible matrix. The polymer fibers may then be selectively dissolved leaving only a biocompatible gel scaffold with the pores formed by the dissolved polymer fibers. The scaffolds may be used in, among other applications, the repair of central and peripheral nerves. Scaffolds for the repair of peripheral nerves may include a reservoir for the sustained release of nerve growth factor. The scaffolds may also include a multifunctional polyelectrolyte layer for the sustained release of nerve growth factor and enhance biocompatibility.

Evaluation of Retinal Changes in Progressive Supranuclear Palsy and Parkinson Disease.

PubMed

Gulmez Sevim, Duygu; Unlu, Metin; Gultekin, Murat; Karaca, Cagatay; Mirza, Meral; Mirza, Galip Ertugrul

2018-06-01

Differentiating Parkinson disease (PD) from progressive supranuclear palsy (PSP) can be challenging early in the clinical course. The aim of our study was to see if specific retinal changes could serve as a distinguishing feature. We used spectral domain optical coherence tomography (SD-OCT) with automatic segmentation to measure peripapillary nerve fiber layer thickness and the thickness and volume of retinal layers at the macula. Thicknesses of superior peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell layer, inner plexiform layer, inner nuclear layer, and macular volume were more affected in PSP compared with PD (P < 0.05). Thicker inferotemporal pRNFL and lower macular volume were detected in levodopa users compared with nonusers in patients with PD. PD and PSP are associated with distinct changes in retinal morphology, which can be assessed with SD-OCT.

The Changing Sensory and Sympathetic Innervation of the Young, Adult and Aging Mouse Femur.

PubMed

Chartier, Stephane R; Mitchell, Stefanie A T; Majuta, Lisa A; Mantyh, Patrick W

2018-02-10

Although bone is continually being remodeled and ultimately declines with aging, little is known whether similar changes occur in the sensory and sympathetic nerve fibers that innervate bone. Here, immunohistochemistry and confocal microscopy were used to examine changes in the sensory and sympathetic nerve fibers that innervate the young (10 days post-partum), adult (3 months) and aging (24 months) C57Bl/6 mouse femur. In all three ages examined, the periosteum was the most densely innervated bone compartment. With aging, the total number of sensory and sympathetic nerve fibers clearly declines as the cambium layer of the periosteum dramatically thins. Yet even in the aging femur, there remains a dense sensory and sympathetic innervation of the periosteum. In cortical bone, sensory and sympathetic nerve fibers are largely confined to vascularized Haversian canals and while there is no significant decline in the density of sensory fibers, there was a 75% reduction in sympathetic nerve fibers in the aging vs. adult cortical bone. In contrast, in the bone marrow the overall density/unit area of both sensory and sympathetic nerve fibers appeared to remain largely unchanged across the lifespan. The preferential preservation of sensory nerve fibers suggests that even as bone itself undergoes a marked decline with age, the nociceptors that detect injury and signal skeletal pain remain relatively intact. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Survey of Nerve Fiber Layer Thickness in Anisometropic and Strabismic Amblyopia.

PubMed

Soltani Moghaddam, Reza; Medghalchi, Abdolreza; Alizadeh, Yousef

2017-01-01

. To investigate the effect of anisometropic and strabismic amblyopia on the nerve fiber layer thickness. This cross-sectional study was done on 54 amblyopic subjects, equally in both strabismic and anisometropic groups. The thickness otonerve fiber layer measured in superior, inferior, nasal, temporal quadrants and as a whole in both eyes of both groups. The means of thickness were compared in amblyopic and sound eyes. In strabismus group, the average nerve fiber layer thickness of the sound eye , in superior, inferior, nasal and temporal quadrants and as a whole were 113.23±14, 117.37±25, 68.96±6, 69.55±14 and 93.40±8 microns respectively. In amblyopic eyes of the same group, these measurements were 103.11±18, 67.74±11, and 69.59±16 and 89.59±12 microns in superior, inferior, nasal, temporal quadrants and as whole respectively. In anisometropic groups, the sound eye measurements were as 130.96±22, 129.07±29, 80.62±12, and 83.88±20 and 107.7±13 microns in superior, inferior, nasal and temporal quadrants and as a whole orderly. In amblyopic eyes of this group the mean thicknesses were 115.63±29, 133.15±25, 78.8±15, 80.2±16 and 109.17±21 microns in superior, inferior, nasal, temporal quadrants and as a whole respectively. Statistically, there were no significant differences between amblyopic and sound eyes (P>0.5). Our study did not support any significant change in a nerve fiber layer thickness of amblyopic patients; however, decreased thickness in superior and nasal quadrants of strabismic amblyopia and except inferior quadrant and as a whole. These measurements may be a clue for management and prognosis of amblyopia in old age.

African Descent and Glaucoma Evaluation Study (ADAGES)

PubMed Central

Girkin, Christopher A.; Sample, Pamela A.; Liebmann, Jeffrey M.; Jain, Sonia; Bowd, Christopher; Becerra, Lida M.; Medeiros, Felipe A.; Racette, Lyne; Dirkes, Keri A.; Weinreb, Robert N.; Zangwill, Linda M.

2010-01-01

Objective To define differences in optic disc, retinal nerve fiber layer, and macular structure between healthy participants of African (AD) and European descent (ED) using quantitative imaging techniques in the African Descent and Glaucoma Evaluation Study (ADAGES). Methods Reliable images were obtained using stereoscopic photography, confocal scanning laser ophthalmoscopy (Heidelberg retina tomography [HRT]), and optical coherence tomography (OCT) for 648 healthy subjects in ADAGES. Findings were compared and adjusted for age, optic disc area, and reference plane height where appropriate. Results The AD participants had significantly greater optic disc area on HRT (2.06 mm2; P<.001) and OCT (2.47 mm2; P<.001) and a deeper HRT cup depth than the ED group (P<.001). Retinal nerve fiber layer thickness was greater in the AD group except within the temporal region, where it was significantly thinner. Central macular thickness and volume were less in the AD group. Conclusions Most of the variations in optic nerve morphologic characteristics between the AD and ED groups are due to differences in disc area. However, differences remain in HRT cup depth, OCT macular thickness and volume, and OCT retinal nerve fiber layer thickness independent of these variables. These differences should be considered in the determination of disease status. PMID:20457974

Complex regional pain syndrome type I (RSD): pathology of skeletal muscle and peripheral nerve.

PubMed

van der Laan, L; ter Laak, H J; Gabreëls-Festen, A; Gabreëls, F; Goris, R J

1998-07-01

Reflex sympathetic dystrophy (RSD) (recently reclassified as complex regional pain syndrome type I) is a syndrome occurring in extremities and, when chronic, results in severe disability and untractable pain. RSD may be accompanied by neurologic symptoms even when there is no previous neurologic lesion. There is no consensus as to the pathogenic mechanism involved in RSD. To gain insight into the pathophysiology of RSD, we studied histopathology of skeletal muscle and peripheral nerve from patients with chronic RSD in a lower extremity. In eight patients with chronic RSD, an above-the-knee amputation was performed because of a nonfunctional limb. Specimens of sural nerves, tibial nerves, common peroneal nerves, gastrocnemius muscles, and soleus muscles were obtained from the amputated legs and analyzed by light and electron microscopy. In all patients, the affected leg showed similar neurologic symptoms such as spontaneous pain, hyperpathy, allodynia, paresis, and anesthesia dolorosa. The nerves showed no consistent abnormalities of myelinated fibers. In four patients, the C-fibers showed electron microscopic pathology. In all patients, the gastrocnemius and soleus muscle specimens showed a decrease of type I fibers, an increase of lipofuscin pigment, atrophic fibers, and severely thickened basal membrane layers of the capillaries. In chronic RSD, efferent nerve fibers were histologically unaffected; from afferent fibers, only C-fibers showed histopathologic abnormalities. Skeletal muscle showed a variety of histopathologic findings, which are similar to the histologic abnormalities found in muscles of patients with diabetes.

The Relationship between Retinal Ganglion Cell Axon Constituents and Retinal Nerve Fiber Layer Birefringence in the Primate

PubMed Central

Pocock, Ginger M.; Aranibar, Roberto G.; Kemp, Nate J.; Specht, Charles S.; Markey, Mia K.; Rylander, H.G.

2009-01-01

Purpose To determine the degree of correlation between spatial characteristics of the retinal nerve fiber layer (RNFL) birefringence (ΔnRNFL) surrounding the optic nerve head (ONH) with the corresponding anatomy of retinal ganglion cell (RGC) axons and their respective organelles. Methods RNFL phase retardation per unit depth (PR/UD, proportional to ΔnRNFL) was measured in two cynomolgus monkeys using enhanced polarization-sensitive optical coherence tomography (EPS-OCT). The monkeys were perfused with glutaraldehyde and eyes were enucleated and prepared for transmission electron microscopy (TEM) histological analysis. Morphological measurements from TEM images were used to estimate values of neurotubule density (ρRNFL), axoplasmic area (Ax) mode, axon area (Aa) mode, slope (u) of neurotubule number versus axoplasmic area [neurotubule packing density], fractional area of axoplasm in the nerve fiber bundle (f), mitochondrial fractional area in the nerve fiber bundle (xm), mitochondriated axon profile fraction (mp), and length of axonal membrane profiles per unit nerve fiber bundle area (Lam/Ab). Registered PR/UD and morphological parameters from corresponding angular sections were then correlated using Pearson’s correlation and multi-level models. Results In one eye, there was a statistically significant correlation between PR/UD and ρRNFL (r = 0.67, P =0.005) and between PR/UD and neurotubule packing density (r = 0.70, P = 0.002). Correlation coefficients of r = 0.81 (P=0.01) and r = 0.50 (P = 0.05) were observed between PR/UD and (Ax) mode for each respective subject. Conclusion Neurotubules are the primary source of birefringence in the RNFL of the primate retina. PMID:19494208

Foveomacular schisis in juvenile X-linked retinoschisis: an optical coherence tomography study.

PubMed

Yu, Jia; Ni, Yingqin; Keane, Pearse A; Jiang, Chunhui; Wang, Wenji; Xu, Gezhi

2010-06-01

To explore the structural features of juvenile X-linked retinoschisis using spectral-domain optical coherence tomography (OCT). Retrospective, observational cross-sectional study. Eighteen male patients (34 eyes) who were diagnosed with juvenile X-linked retinoschisis at the Eye & ENT Hospital of Fudan University over an 18-month period were included. Their OCT images, which were obtained using spectral-domain OCT (Cirrus HD-OCT; Carl Zeiss Meditec), were analyzed. The anatomic location of the schisis cavity in juvenile X-linked retinoschisis was characterized by direct inspection of OCT images. On OCT, the schisis cavity was visible at the fovea in all 34 eyes, and it was associated with increased retinal thickness. Schisis was present at the retinal nerve fiber layer in 4 eyes, at the inner nuclear layer in 29 eyes, and at the outer nuclear layer/outer plexiform layer in 22 eyes. In most cases, widespread foveomacular schisis was detected using OCT; however, in 9 eyes (6 patients), the schisis was confined to the fovea. Schisis of the inner nuclear layer and outer nuclear layer/outer plexiform layer almost always involved the foveal center, but retinal nerve fiber layer schisis was seen only in the parafoveal area. Despite conventional wisdom, in patients with X-linked retinoschisis, the schisis cavity can occur in a number of different layers of the neurosensory retina (retinal nerve fiber layer, inner nuclear layer, and outer nuclear layer/outer plexiform layer). In addition, different forms of schisis may affect different locations in the macula (foveal vs parafoveal), and, in most eyes, the schisis involves the entire foveomacular region. Copyright 2010 Elsevier Inc. All rights reserved.

Retinal and Optic Nerve Degeneration in Patients with Multiple Sclerosis Followed up for 5 Years.

PubMed

Garcia-Martin, Elena; Ara, Jose R; Martin, Jesus; Almarcegui, Carmen; Dolz, Isabel; Vilades, Elisa; Gil-Arribas, Laura; Fernandez, Francisco J; Polo, Vicente; Larrosa, Jose M; Pablo, Luis E; Satue, Maria

2017-05-01

To quantify retinal nerve fiber layer (RNFL) changes in patients with multiple sclerosis (MS) and healthy controls with a 5-year follow-up and to analyze correlations between disability progression and RNFL degeneration. Observational and longitudinal study. One hundred patients with relapsing-remitting MS and 50 healthy controls. All participants underwent a complete ophthalmic and electrophysiologic exploration and were re-evaluated annually for 5 years. Visual acuity (Snellen chart), color vision (Ishihara pseudoisochromatic plates), visual field examination, optical coherence tomography (OCT), scanning laser polarimetry (SLP), and visual evoked potentials. Expanded Disability Status Scale (EDSS) scores, disease duration, treatments, prior optic neuritis episodes, and quality of life (QOL; based on the 54-item Multiple Sclerosis Quality of Life Scale score). Optical coherence tomography (OCT) revealed changes in all RNFL thicknesses in both groups. In the MS group, changes were detected in average thickness and in the mean deviation using the GDx-VCC nerve fiber analyzer (Laser Diagnostic Technologies, San Diego, CA) and in the P100 latency of visual evoked potentials; no changes were detected in visual acuity, color vision, or visual fields. Optical coherence tomography showed greater differences in the inferior and temporal RNFL thicknesses in both groups. In MS patients only, OCT revealed a moderate correlation between the increase in EDSS and temporal and superior RNFL thinning. Temporal RNFL thinning based on OCT results was correlated moderately with decreased QOL. Multiple sclerosis patients exhibit a progressive axonal loss in the optic nerve fiber layer. Retinal nerve fiber layer thinning based on OCT results is a useful marker for assessing MS progression and correlates with increased disability and reduced QOL. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Comparative study of the retinal nerve fibre layer thickness performed with optical coherence tomography and GDx scanning laser polarimetry in patients with primary open-angle glaucoma.

PubMed

Wasyluk, Jaromir T; Jankowska-Lech, Irmina; Terelak-Borys, Barbara; Grabska-Liberek, Iwona

2012-03-01

We compared the parameters of retinal nerve fibre layer in patients with advanced glaucoma with the use of different OCT (Optical Coherence Tomograph) devices in relation to analogical measurements performed with GDx VCC (Nerve Fiber Analyzer with Variable Corneal Compensation) scanning laser polarimetry. Study subjects had advanced primary open-angle glaucoma, previously treated conservatively, diagnosed and confirmed by additional examinations (visual field, ophthalmoscopy of optic nerve, gonioscopy), A total of 10 patients were enrolled (9 women and 1 man), aged 18-70 years of age. Nineteen eyes with advanced glaucomatous neuropathy were examined. 1) Performing a threshold perimetry Octopus, G2 strategy and ophthalmoscopy of optic nerve to confirm the presence of advanced primary open-angle glaucoma; 2) performing a GDx VCC scanning laser polarimetry of retinal nerve fibre layer; 3) measuring the retinal nerve fibre layer thickness with 3 different optical coherence tomographs. The parameters of the retinal nerve fibre layer thickness are highly correlated between the GDx and OCT Stratus and 3D OCT-1000 devices in mean retinal nerve fibre layer thickness, retinal nerve fibre layer thickness in the upper sector, and correlation of NFI (GDx) with mean retinal nerve fibre layer thickness in OCT examinations. Absolute values of the retinal nerve fibre layer thickness (measured in µm) differ significantly between GDx and all OCT devices. Examination with OCT devices is a sensitive diagnostic method of glaucoma, with good correlation with the results of GDx scanning laser polarimetry of the patients.

Effect of diabetic retinopathy and panretinal photocoagulation on retinal nerve fiber layer and optic nerve appearance.

PubMed

Lim, Michele C; Tanimoto, Suzana A; Furlani, Bruno A; Lum, Brent; Pinto, Luciano M; Eliason, David; Prata, Tiago S; Brandt, James D; Morse, Lawrence S; Park, Susanna S; Melo, Luiz A S

2009-07-01

To determine if panretinal photocoagulation (PRP) alters retinal nerve fiber layer (RNFL) thickness and optic nerve appearance. Patients with diabetes who did and did not undergo PRP and nondiabetic control subjects were enrolled in a prospective study. Participants underwent optical coherence tomography of the peripapillary retina and optic nerve. Stereoscopic optic nerve photographs were graded in a masked fashion. Ninety-four eyes of 48 healthy individuals, 89 eyes of 55 diabetic patients who did not undergo PRP, and 37 eyes of 24 subjects with diabetes who underwent PRP were included in this study. Eyes that had been treated with PRP had thinner peripapillary RNFL compared with the other groups; this was statistically significantly different in the inferior (P = .004) and nasal (P = .003) regions. Optic nerve cupping did not increase with severity of disease classification, but the proportion of optic nerves graded as suspicious for glaucoma or as having nonglaucomatous optic neuropathy did (P = .008). These grading categories were associated with thinner RNFL measurements. Diabetic eyes that have been treated with PRP have thinner RNFL than nondiabetic eyes. Optic nerves in eyes treated with PRP are more likely to be graded as abnormal, but their appearance is not necessarily glaucomatous and may be related to thinning of the RNFL.

Retinal Nerve Fiber Layer Segmentation on FD-OCT Scans of Normal Subjects and Glaucoma Patients.

PubMed

Mayer, Markus A; Hornegger, Joachim; Mardin, Christian Y; Tornow, Ralf P

2010-11-08

Automated measurements of the retinal nerve fiber layer thickness on circular OCT B-Scans provide physicians additional parameters for glaucoma diagnosis. We propose a novel retinal nerve fiber layer segmentation algorithm for frequency domain data that can be applied on scans from both normal healthy subjects, as well as glaucoma patients, using the same set of parameters. In addition, the algorithm remains almost unaffected by image quality. The main part of the segmentation process is based on the minimization of an energy function consisting of gradient and local smoothing terms. A quantitative evaluation comparing the automated segmentation results to manually corrected segmentations from three reviewers is performed. A total of 72 scans from glaucoma patients and 132 scans from normal subjects, all from different persons, composed the database for the evaluation of the segmentation algorithm. A mean absolute error per A-Scan of 2.9 µm was achieved on glaucomatous eyes, and 3.6 µm on healthy eyes. The mean absolute segmentation error over all A-Scans lies below 10 µm on 95.1% of the images. Thus our approach provides a reliable tool for extracting diagnostic relevant parameters from OCT B-Scans for glaucoma diagnosis.

Retinal Nerve Fiber Layer Segmentation on FD-OCT Scans of Normal Subjects and Glaucoma Patients

PubMed Central

Mayer, Markus A.; Hornegger, Joachim; Mardin, Christian Y.; Tornow, Ralf P.

2010-01-01

Automated measurements of the retinal nerve fiber layer thickness on circular OCT B-Scans provide physicians additional parameters for glaucoma diagnosis. We propose a novel retinal nerve fiber layer segmentation algorithm for frequency domain data that can be applied on scans from both normal healthy subjects, as well as glaucoma patients, using the same set of parameters. In addition, the algorithm remains almost unaffected by image quality. The main part of the segmentation process is based on the minimization of an energy function consisting of gradient and local smoothing terms. A quantitative evaluation comparing the automated segmentation results to manually corrected segmentations from three reviewers is performed. A total of 72 scans from glaucoma patients and 132 scans from normal subjects, all from different persons, composed the database for the evaluation of the segmentation algorithm. A mean absolute error per A-Scan of 2.9 µm was achieved on glaucomatous eyes, and 3.6 µm on healthy eyes. The mean absolute segmentation error over all A-Scans lies below 10 µm on 95.1% of the images. Thus our approach provides a reliable tool for extracting diagnostic relevant parameters from OCT B-Scans for glaucoma diagnosis. PMID:21258556

Effects of Schwann cell alignment along the oriented electrospun chitosan nanofibers on nerve regeneration.

PubMed

Wang, Wei; Itoh, Soichiro; Konno, Katsumi; Kikkawa, Takeshi; Ichinose, Shizuko; Sakai, Katsuyoshi; Ohkuma, Tsuneo; Watabe, Kazuhiko

2009-12-15

We have constructed a chitosan nonwoven nanofiber mesh tube consisting of oriented fibers by the electrospinning method. The efficacy of oriented nanofibers on Schwann cell alignment and positive effect of this tube on peripheral nerve regeneration were confirmed. The physical properties of the chitosan nanofiber mesh sheets prepared by electrospinning with or without fiber orientation were characterized. Then, immortalized Schwann cells were cultured on these sheets. Furthermore, the chitosan nanofiber mesh tubes with or without orientation, and bilayered chitosan mesh tube with an inner layer of oriented nanofibers and an outer layer of randomized nanofibers were bridgegrafted into rat sciatic nerve defect. As a result of fiber orientation, the tensile strength along the axis of the sheet increased. Because Schwann cells aligned along the nanofibers, oriented fibrous sheets could exhibit a Schwann cell column. Functional recovery and electrophysiological recovery occurred in time in the oriented group as well as in the bilayered group, and approximately matched those in the isograft. Furthermore, histological analysis revealed that the sprouting of myelinated axons occurred vigorously followed by axonal maturation in the isograft, oriented, and bilayered group in the order. The oriented chitosan nanofiber mesh tube may be a promising substitute for autogenous nerve graft.

Comparative study of the retinal nerve fibre layer thickness performed with optical coherence tomography and GDx scanning laser polarimetry in patients with primary open-angle glaucoma

PubMed Central

Wasyluk, Jaromir T.; Jankowska-Lech, Irmina; Terelak-Borys, Barbara; Grabska-Liberek, Iwona

2012-01-01

Summary Background We compared the parameters of retinal nerve fibre layer in patients with advanced glaucoma with the use of different OCT (Optical Coherence Tomograph) devices in relation to analogical measurements performed with GDx VCC (Nerve Fiber Analyzer with Variable Corneal Compensation) scanning laser polarimetry. Material/Methods Study subjects had advanced primary open-angle glaucoma, previously treated conservatively, diagnosed and confirmed by additional examinations (visual field, ophthalmoscopy of optic nerve, gonioscopy), A total of 10 patients were enrolled (9 women and 1 man), aged 18–70 years of age. Nineteen eyes with advanced glaucomatous neuropathy were examined. 1) Performing a threshold perimetry Octopus, G2 strategy and ophthalmoscopy of optic nerve to confirm the presence of advanced primary open-angle glaucoma; 2) performing a GDx VCC scanning laser polarimetry of retinal nerve fibre layer; 3) measuring the retinal nerve fibre layer thickness with 3 different optical coherence tomographs. Results The parameters of the retinal nerve fibre layer thickness are highly correlated between the GDx and OCT Stratus and 3D OCT-1000 devices in mean retinal nerve fibre layer thickness, retinal nerve fibre layer thickness in the upper sector, and correlation of NFI (GDx) with mean retinal nerve fibre layer thickness in OCT examinations. Absolute values of the retinal nerve fibre layer thickness (measured in μm) differ significantly between GDx and all OCT devices. Conclusions Examination with OCT devices is a sensitive diagnostic method of glaucoma, with good correlation with the results of GDx scanning laser polarimetry of the patients. PMID:22367131

Optical coherence tomography platforms and parameters for glaucoma diagnosis and progression.

PubMed

Mwanza, Jean-Claude; Budenz, Donald L

2016-03-01

Optical coherence tomography (OCT) aids in the diagnosis and long-term monitoring of various ocular diseases, including glaucoma. Initially, the retinal nerve fiber layer was the only OCT structural parameter used in glaucoma. Subsequent research has resulted in more retinal and optic nerve head parameters. In addition, OCT is being investigated for its ability to assess ocular hemodynamics. This review summarizes these spectral domain-optical coherence tomography (SDOCT) parameters in the context of glaucoma. Several new SDOCT retinal nerve fiber layer, optic nerve head, and macular parameters with good glaucoma diagnostic ability have been added to existing ones recently. The combination of SDOCT and Doppler or angiography has also resulted in hemodynamic parameters that may prove to be useful in the functional assessment in glaucoma. OCT technology is advancing not only as a tool for structural assessment, but also as a multimodality tool to assess both structure and function to enhance our understanding of glaucoma, and ultimately clinical decisions.

ACUTE ZONAL OCCULT OUTER RETINOPATHY: Structural and Functional Analysis Across the Transition Zone Between Healthy and Diseased Retina.

PubMed

Duncker, Tobias; Lee, Winston; Jiang, Fan; Ramachandran, Rithambara; Hood, Donald C; Tsang, Stephen H; Sparrow, Janet R; Greenstein, Vivienne C

2018-01-01

To assess structure and function across the transition zone (TZ) between relatively healthy and diseased retina in acute zonal occult outer retinopathy. Six patients (6 eyes; age 22-71 years) with acute zonal occult outer retinopathy were studied. Spectral-domain optical coherence tomography, fundus autofluorescence, near-infrared reflectance, color fundus photography, and fundus perimetry were performed and images were registered to each other. The retinal layers of the spectral-domain optical coherence tomography scans were segmented and the thicknesses of two outer retinal layers, that is, the total receptor and outer segment plus layers, and the retinal nerve fiber layer were measured. All eyes showed a TZ on multimodal imaging. On spectral-domain optical coherence tomography, the TZ was in the nasal retina at varying distances from the fovea. For all eyes, it was associated with loss of the ellipsoid zone band, significant thinning of the two outer retinal layers, and in three eyes with thickening of the retinal nerve fiber layer. On fundus autofluorescence, all eyes had a clearly demarcated peripapillary area of abnormal fundus autofluorescence delimited by a border of high autofluorescence; the latter was associated with loss of the ellipsoid zone band and with a change from relatively normal to markedly decreased or nonrecordable visual sensitivity on fundus perimetry. The results of multimodal imaging clarified the TZ in acute zonal occult outer retinopathy. The TZ was outlined by a distinct high autofluorescence border that correlated with loss of the ellipsoid zone band on spectral-domain optical coherence tomography. However, in fundus areas that seemed healthy on fundus autofluorescence, thinning of the outer retinal layers and thickening of the retinal nerve fiber layer were observed near the TZ. The TZ was also characterized by a decrease in visual sensitivity.

Morphological and neurochemical differences in peptidergic nerve fibers of the mouse vagina.

PubMed

Barry, Christine M; Ji, Esther; Sharma, Harman; Beukes, Lara; Vilimas, Patricia I; DeGraaf, Yvette C; Matusica, Dusan; Haberberger, Rainer V

2017-07-01

The vagina is innervated by a complex arrangement of sensory, sympathetic, and parasympathetic nerve fibers that contain classical transmitters plus an array of neuropeptides and enzymes known to regulate diverse processes including blood flow and nociception. The neurochemical characteristics and distributions of peptide-containing nerves in the mouse vagina are unknown. This study used multiple labeling immunohistochemistry, confocal maging and analysis to investigate the presence and colocalization of the peptides vasoactive intestinal polypeptide (VIP), calcitonin-gene related peptide (CGRP), substance P (SP), neuropeptide tyrosine (NPY), and the nitric oxide synthesizing enzyme neuronal nitric oxide synthase (nNOS) in nerve fibers of the murine vaginal wall. We compared cervical and vulvar areas of the vagina in young nullipara and older multipara C57Bl/6 mice, and identified differences including that small ganglia were restricted to cervical segments, epithelial fibers were mainly present in vulvar segments and most nerve fibers were found in the lamina propria of the cervical region of the vagina, where a higher number of fibers containing immunoreactivity for VIP, CGRP, SP, or nNOS were found. Two populations of VIP-containing fibers were identified: fibers containing CGRP and fibers containing VIP but not CGRP. Differences between young and older mice were present in multiple layers of the vaginal wall, with older mice showing overall loss of innervation of epithelium of the proximal vagina and reduced proportions of VIP, CGRP, and SP containing nerve fibers in the distal epithelium. The distal vagina also showed increased vascularization and perivascular fibers containing NPY. Immunolabeling of ganglia associated with the vagina indicated the likely origin of some peptidergic fibers. Our results reveal regional differences and age- or parity-related changes in innervation of the mouse vagina, effecting the distribution of neuropeptides with diverse roles in function of the female genital tract. © 2017 Wiley Periodicals, Inc.

Spectral domain polarization-sensitive optical coherence tomography at 850 nm

NASA Astrophysics Data System (ADS)

Cense, Barry; Chen, Teresa C.; Mujat, Mircea; Joo, Chulmin; Akkin, Taner; Park, B. H.; Pierce, Mark C.; Yun, Andy; Bouma, Brett E.; Tearney, Guillermo J.; de Boer, Johannes F.

2005-04-01

Spectral-Domain Polarization-Sensitive Optical Coherence Tomography (SD-PS-OCT) is a technique developed to measure the thickness and birefringence of the nerve fiber layer in vivo as a tool for the early diagnosis of glaucoma. A clinical SD-PS-OCT system was developed and scans were made around the optic nerve head (ONH) using ten concentric circles of increasing diameter. One healthy volunteer was imaged. Retinal nerve fiber layer thickness and birefringence information was extracted from the data. Polarization-sensitive OCT images were acquired at video rate (29 frames per second (fps), 1000 A-lines / frame) and at 7 fps (1000 A-lines / frame). The last setting improved the signal to noise ratio by approximately 6 dB. Birefringence measurements on the healthy volunteer gave similar results as earlier reported values that were obtained with a time-domain setup. The measurement time was reduced from more than a minute to less than a second.

The visceromotor and somatic afferent nerves of the penis.

PubMed

Diallo, Djibril; Zaitouna, Mazen; Alsaid, Bayan; Quillard, Jeanine; Ba, Nathalie; Allodji, Rodrigue Sètchéou; Benoit, Gérard; Bedretdinova, Dina; Bessede, Thomas

2015-05-01

Innervation of the penis supports erectile and sensory functions. This article aims to study the efferent autonomic (visceromotor) and afferent somatic (sensory) nervous systems of the penis and to investigate how these systems relate to vascular pathways. Penises obtained from five adult cadavers were studied via computer-assisted anatomic dissection (CAAD). The number of autonomic and somatic nerve fibers was compared using the Kruskal-Wallis test. Proximally, penile innervation was mainly somatic in the extra-albugineal sector and mainly autonomic in the intracavernosal sector. Distally, both sectors were almost exclusively supplied by somatic nerve fibers, except the intrapenile vascular anastomoses that accompanied both somatic and autonomic (nitrergic) fibers. From this point, the neural immunolabeling within perivascular nerve fibers was mixed (somatic labeling and autonomic labeling). Accessory afferent, extra-albugineal pathways supplied the outer layers of the penis. There is a major change in the functional type of innervation between the proximal and distal parts of the intracavernosal sector of the penis. In addition to the pelvis and the hilum of the penis, the intrapenile neurovascular routes are the third level where the efferent autonomic (visceromotor) and the afferent somatic (sensory) penile nerve fibers are close. Intrapenile neurovascular pathways define a proximal penile segment, which guarantees erectile rigidity, and a sensory distal segment. © 2015 International Society for Sexual Medicine.

Ulex europaeus I and glycine max bind to the human olfactory bulb.

PubMed

Nagao, M; Oka, N; Kamo, H; Akiguchi, I; Kimura, J

1993-12-24

The distribution of binding sites for the fucose-selective lectin Ulex europaeus I and the terminal N-acetylgalactosamine-selective lectin glycine max in the human olfactory bulb were studied. These lectins bound to primary olfactory axons in the olfactory nerve layer and the glomerular layer. They also bound to fibers located in the deeper layers such as the external plexiform layer and the granular layer. Furthermore they projected to the olfactory stalk but not in the cerebrum. The deeper projections of the lectin binding fibers may affect the function of the olfactory bulb in humans.

Retinotopic and temporal organization of the optic nerve and tracts in the adult goldfish.

PubMed

Bunt, S M

1982-04-10

In order to investigate the role of the different factors controlling the pathways and termination sites of growing axons, selected optic fibers were traced from the eye to the tectum in adult goldfish either by filling them with HRP, or by severing a group of fibers and tracing their degeneration in 2 micrometers plastic sections stained with toluidine blue. Some fish received more than one lesion and others received both lesions and HRP applications. Two major rearrangements of the optic fibers were identified, one at the exit from the eye, the other within the optic tracts. Near the eye the optic fibers appear to be guided by the conformation of the underlying tissue planes that they encounter. The most recently added fibers, from the peripheral retina, grow over the vitread surface of the older fibers toward the blood vessel in the center of the optic nerve head. Behind the eye the fibers follow this blood vessel until it leaves the side of the optic nerve, and the fibers from peripheral retina are left as a single group on the ventral edge of the optic nerve cross section. As a consequence of this pattern of fiber growth the fibers form an orderly temporal sequence in the optic nerve, with the oldest fibers from the central retina on one side of the nerve and the youngest from peripheral retina on the other. In addition, the fibers are ordered topographically at right angles to this central-to-peripheral axis, with fibers from ventral retina on each edge of the nerve, dorsal fibers in the center, and nasal and temporal fibers in between. This arrangement of the optic fibers continues with only a little loss of precision up to the optic tracts. A more radical fiber rearrangement, seemingly incompatible with the fibers simply following tissue planes occurs within the optic tracts. Each newly arriving set of fibers grows over the surface of the optic tracts so that the older fibers come to lie deepest in the tracts. This segregation of fibers of different ages ensures that the rearrangement is limited to each layer of fibers. The abrupt reorganization of the fibers occurs as the tracts split around the nucleus rotundus to form the brachia of the optic tracts. The fibers are then arranged with temporal fibers nearest the nucleus rotundus and nasal fibers on the opposite edges of the brachia. From this point the fibers grow out over the tectal surface to their termination sites with only minimal rearrangements. Therefore the optic fiber rearrangements show evidence of several different sorts of constraints acting on the fibers at separate points in the optic pathway, each contributing to the final orderly arrangement of the fibers on the optic tectum.

Renaut bodies in nerves of the trunk of the African elephant, Loxodonta africana.

PubMed

Witter, Kirsti; Egger, Gunter F; Boeck, Peter

2007-05-01

Renaut bodies are loosely textured, cell-sparse structures in the subperineurial space of peripheral nerves, frequently found at sites of nerve entrapment. The trunk of the elephant is a mobile, richly innervated organ, which serves for food gathering, object grasping and as a tactile organ. These functions of the trunk lead to distortion and mechanical compression of its nerves, which can therefore be expected to contain numerous Renaut bodies. Samples of the trunk wall of an adult African elephant (Loxodonta africana) were examined histologically using conventional staining methods, immunohistochemistry, and lectin histochemistry. Architecture of nerve plexuses and occurrence of Renaut bodies in the elephant trunk were compared with those in tissues surrounding the nasal vestibule of the pig. Prominent nerve plexuses were found in all layers of the elephant trunk. Almost all (81%) nerve profiles contained Renaut bodies, a basophilic, discrete subperineurial layer resembling cushions around the nerve core. In contrast, Renaut bodies were seen in only 15% of nerve profiles in the porcine nasal vestibule. Within Renaut bodies, fusiform fibroblasts and round, ruff-like cells were placed into a matrix of acidic glycosaminoglycans with delicate collagen and very few reticular fibers. The turgor of this matrix is thought to protect nerves against compression and shearing strain. Renaut bodies are readily stained with alcian blue (pH 2.5) favorably in combination with immunohistochemical markers of nerve fibers. They should be regarded as a physiological response to repeated mechanical insults and are distinct from pathological alterations. alterations. (c) 2007 Wiley-Liss, Inc.

Distribution of FMRFamide-like immunoreactivity in the brain, retina and nervus terminalis of the sockeye salmon parr, Oncorhynchus nerka.

PubMed

Ostholm, T; Ekström, P; Ebbesson, S O

1990-09-01

Neurons displaying FMRFamide(Phe - Met - Arg - Phe - NH2)-like immunoreactivity have recently been implicated in neural plasticity in salmon. We now extend these findings by describing the extent of the FMRF-like immunoreactive (FMRF-IR) system in the brain, retina and olfactory system of sockeye salmon parr using the indirect peroxidase anti-peroxidase technique. FMRF-IR perikarya were found in the periventricular hypothalamus, mesencephalic laminar nucleus, nucleus nervi terminalis and retina (presumed amacrine cells), and along the olfactory nerves. FMRF-IR fibers were distributed throughout the brain with highest densities in the ventral area of the telencephalon, in the medial forebrain bundle, and at the borders between layers III/IV and IV/V in the optic tectum. High densities of immunoreactive fibers were also observed in the area around the torus semicircularis, in the medial hypothalamus, median raphe, ventromedial tegmentum, and central gray. In the retina, immunopositive fibers were localized to the inner plexiform layer, but several fiber elements were also found in the outer plexiform layer. The olfactory system displayed FMRF-IR fibers in the epithelium and along the olfactory nerves. These findings differ from those reported in other species as follows: (i) FMRF-IR cells in the retina have not previously been reported in teleosts; (ii) the presence of FMRF-IR fibers in the outer plexiform layer of the retina is a new finding for any species; (iii) the occurrence of immunopositive cells in the mesencephalic laminar nucleus has to our knowledge not been demonstrated previously.

Scanning electron microscopy of echinoid podia.

PubMed

Florey, E; Cahill, M A

1982-01-01

Tube feet of the sea urchin Strongylocentrotus franciscanus were studied with the scanning electron microscope (SEM). By use of fractured preparations it was possible to obtain views of all components of the layered tube-foot wall. The outer epithelium was found to bear tufts of cilia possibly belonging to sensory cells. The nerve plexus was clearly revealed as being composed of bundles of varicose axons. The basal lamina, which covers the outer and inner surfaces of the connective tissue layer, was found to be a mechanically resistant and elastic membrane. The connective tissue appears as dense bundles of (collagen) fibers. The luminal epithelium (coelothelium) is a single layer of flagellated collar cells. There is no indication that the muscle fibers, which insert on the inner basal lamina of the connective tissue layer are innervated by axons from the basi-epithelial nerve plexus. The results agree with previous conclusions concerning tube-foot structure based on transmission electron microscopy, and provide additional information, particularly with regard to the outer and inner epithelia.

Optical coherence tomography measurement of the retinal nerve fiber layer in normal and juvenile glaucomatous eyes.

PubMed

Mrugacz, Malgorzata; Bakunowicz-Lazarczyk, Alina

2005-01-01

The aim of this study was to quantitatively assess and compare the thickness of the retinal nerve fiber layer (RNFL) in normal and glaucomatous eyes of children using the optical coherence tomograph. The mean RNFL thickness of normal eyes (n=26) was compared with that of glaucomatous eyes (n=26). The eyes were classified into diagnostic groups based on conventional ophthalmological physical examination, Humphrey 30-2 visual fields, stereoscopic optic nerve head photography, and optical coherence tomography. The mean RNFL was significantly thinner in glaucomatous eyes than in normal eyes: 95+/-26.3 and 132+/-24.5 microm, respectively. More specifically, the RNFL was significantly thinner in glaucomatous eyes than in normal eyes in the inferior quadrant: 87+/-23.5 and 122+/-24.2 microm, respectively. The mean and inferior quadrant RFNL thicknesses as measured by the optical coherence tomograph showed a statistically significant correlation with glaucoma. Optical coherence tomography may contribute to tracking of juvenile glaucoma progression. Copyright (c) 2005 S. Karger AG, Basel.

Relationship Between Optic Nerve Appearance and Retinal Nerve Fiber Layer Thickness as Explored with Spectral Domain Optical Coherence Tomography

PubMed Central

Aleman, Tomas S.; Huang, Jiayan; Garrity, Sean T.; Carter, Stuart B.; Aleman, Wendy D.; Ying, Gui-shuang; Tamhankar, Madhura A.

2014-01-01

Purpose To study the relationship between the appearance of the optic nerve and the retinal nerve fiber layer (RNFL) thickness determined by spectral domain optical coherence tomography (OCT). Methods Records from patients with spectral domain-OCT imaging in a neuro-ophthalmology practice were reviewed. Eyes with glaucoma/glaucoma suspicion, macular/optic nerve edema, pseudophakia, and with refractive errors > 6D were excluded. Optic nerve appearance by slit lamp biomicroscopy was related to the RNFL thickness by spectral domain-OCT and to visual field results. Results Ninety-one patients (176 eyes; mean age: 49 ± 15 years) were included. Eighty-three eyes (47%) showed optic nerve pallor; 89 eyes (50.6%) showed RNFL thinning (sectoral or average peripapillary). Average peripapillary RNFL thickness in eyes with pallor (mean ± SD = 76 ± 17 μm) was thinner compared to eyes without pallor (91 ± 14 μm, P < 0.001). Optic nerve pallor predicted RNFL thinning with a sensitivity of 69% and a specificity of 75%. Optic nerve appearance predicted RNFL thinning (with a sensitivity and specificity of 81%) when RNFL had thinned by ∼ 40%. Most patients with pallor had RNFL thinning with (66%) or without (25%) visual field loss; the remainder had normal RNFL and fields (5%) or with visual field abnormalities (4%). Conclusions Optic nerve pallor as a predictor of RNFL thinning showed fair sensitivity and specificity, although it is optimally sensitive/specific only when substantial RNFL loss has occurred. Translational Relevance Finding an acceptable relationship between the optic nerve appearance by ophthalmoscopy and spectral domain-OCT RNFL measures will help the clinician's interpretation of the information provided by this technology, which is gaining momentum in neuro-ophthalmic research. PMID:25374773

Immunohistochemical localization of two types of choline acetyltransferase in neurons and sensory cells of the octopus arm.

PubMed

Sakaue, Yuko; Bellier, Jean-Pierre; Kimura, Shin; D'Este, Loredana; Takeuchi, Yoshihiro; Kimura, Hiroshi

2014-01-01

Cholinergic structures in the arm of the cephalopod Octopus vulgaris were studied by immunohistochemistry using specific antisera for two types (common and peripheral) of acetylcholine synthetic enzyme choline acetyltransferase (ChAT): antiserum raised against the rat common type ChAT (cChAT), which is cross-reactive with molluscan cChAT, and antiserum raised against the rat peripheral type ChAT (pChAT), which has been used to delineate peripheral cholinergic structures in vertebrates, but not previously in invertebrates. Western blot analysis of octopus extracts revealed a single pChAT-positive band, suggesting that pChAT antiserum is cross-reactive with an octopus counterpart of rat pChAT. In immunohistochemistry, only neuronal structures of the octopus arm were stained by cChAT and pChAT antisera, although the pattern of distribution clearly differed between the two antisera. cChAT-positive varicose nerve fibers were observed in both the cerebrobrachial tract and neuropil of the axial nerve cord, while pChAT-positive varicose fibers were detected only in the neuropil of the axial nerve cord. After epitope retrieval, pChAT-positive neuronal cells and their processes became visible in all ganglia of the arm, including the axial and intramuscular nerve cords, and in ganglia of suckers. Moreover, pChAT-positive structures also became detectable in nerve fibers connecting the different ganglia, in smooth nerve fibers among muscle layers and dermal connective tissues, and in sensory cells of the suckers. These results suggest that the octopus arm has two types of cholinergic nerves: cChAT-positive nerves from brain ganglia and pChAT-positive nerves that are intrinsic to the arm.

Morphology and Neurochemistry of Rabbit Iris Innervation

PubMed Central

He, Jiucheng; Bazan, Haydee E.P.

2016-01-01

The aim of this study was to map the entire nerve architecture and sensory neuropeptide content of the rabbit iris. Irises from New Zealand rabbits were stained with antibodies against neuronal-class βIII-tubulin, calcitonin gene-related peptide (CGRP) and substance P (SP), and whole-mount images were acquired to build a two-dimensional view of the iridal nerve architecture. After taking images in time-lapse mode, we observed thick nerves running in the iris stroma close to the anterior epithelia, forming four to five stromal nerve rings from the iris periphery to the pupillary margin and sub-branches that connected with each other, constituting the stromal nerve plexus. In the anterior side, fine divisions derivated from the stromal nerves, forming a nerve network-like structure to innervate the superficial anterior border layer, with the pupillary margin having the densest innervation. In the posterior side, the nerve bundles ran along with the pupil dilator muscle in a radial pattern. The morphology of the iris nerves on both sides changed with pupil size. To obtain the relative content of the neuropeptides in the iris, the specimens were double stained with βIII-tubulin and CGRP or SP antibodies. Relative nerve fiber densities for each fiber population were assessed quantitatively by computer-assisted analysis. On the anterior side, CGRP-positive nerve fibers constituted about 61%, while SP-positive nerves constitute about 30.5%, of the total nerve content, which was expressed as βIII tubulin-positive fibers. In addition, in the anterior stroma of the collarette region, there were non-neuronal cells that were positive for SP. On the posterior side, CGRP-positive nerve fibers were about 69% of total nerve content, while SP constituted only up to 20%. Similarly, in the trigeminal ganglia (TG), the number of CGRP-positive neurons significantly outnumbered those that were positive for SP. Also, all the SP-positive neurons were labeled with CGRP. This is the first study to provide a two-dimensional whole mount and a cross-sectional view of the entire iris nerve architecture. Considering the anatomical location, the high expression of CGRP and SP suggests that these neuropeptides may play a role in the pathogenesis of anterior uveitis, glaucoma, cataracts and chronic ocular pain. PMID:25752697

Morphology and neurochemistry of rabbit iris innervation.

PubMed

He, Jiucheng; Bazan, Haydee E P

2015-06-01

The aim of this study was to map the entire nerve architecture and sensory neuropeptide content of the rabbit iris. Irises from New Zealand rabbits were stained with antibodies against neuronal-class βIII-tubulin, calcitonin gene-related peptide (CGRP) and substance P (SP), and whole-mount images were acquired to build a two-dimensional view of the iridal nerve architecture. After taking images in time-lapse mode, we observed thick nerves running in the iris stroma close to the anterior epithelia, forming four to five stromal nerve rings from the iris periphery to the pupillary margin and sub-branches that connected with each other, constituting the stromal nerve plexus. In the anterior side, fine divisions derivated from the stromal nerves, forming a nerve network-like structure to innervate the superficial anterior border layer, with the pupillary margin having the densest innervation. In the posterior side, the nerve bundles ran along with the pupil dilator muscle in a radial pattern. The morphology of the iris nerves on both sides changed with pupil size. To obtain the relative content of the neuropeptides in the iris, the specimens were double stained with βIII-tubulin and CGRP or SP antibodies. Relative nerve fiber densities for each fiber population were assessed quantitatively by computer-assisted analysis. On the anterior side, CGRP-positive nerve fibers constituted about 61%, while SP-positive nerves constitute about 30.5%, of the total nerve content, which was expressed as βIII tubulin-positive fibers. In addition, in the anterior stroma of the collarette region, there were non-neuronal cells that were positive for SP. On the posterior side, CGRP-positive nerve fibers were about 69% of total nerve content, while SP constituted only up to 20%. Similarly, in the trigeminal ganglia (TG), the number of CGRP-positive neurons significantly outnumbered those that were positive for SP. Also, all the SP-positive neurons were labeled with CGRP. This is the first study to provide a two-dimensional whole mount and a cross-sectional view of the entire iris nerve architecture. Considering the anatomical location, the high expression of CGRP and SP suggests that these neuropeptides may play a role in the pathogenesis of anterior uveitis, glaucoma, cataracts and chronic ocular pain. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparison of peripapillary retinal nerve fiber layer loss and visual outcome in fellow eyes following sequential bilateral non-arteritic anterior ischemic optic neuropathy.

PubMed

Dotan, Gad; Kesler, Anat; Naftaliev, Elvira; Skarf, Barry

2015-05-01

To report on the correlation of structural damage to the axons of the optic nerve and visual outcome following bilateral non-arteritic anterior ischemic optic neuropathy. A retrospective review of the medical records of 25 patients with bilateral sequential non-arteritic anterior ischemic optic neuropathy was performed. Outcome measures were peripapillary retinal nerve fiber layer thickness measured with the Stratus optical coherence tomography scanner, visual acuity and visual field loss. Median peripapillary retinal nerve fiber layer (RNFL) thickness, mean deviation (MD) of visual field, and visual acuity of initially involved NAION eyes (54.00 µm, -17.77 decibels (dB), 0.4, respectively) were comparable to the same parameters measured following development of second NAION event in the other eye (53.70 µm, p = 0.740; -16.83 dB, p = 0.692; 0.4, p = 0.942, respectively). In patients with bilateral NAION, there was a significant correlation of peripapillary RNFL thickness (r = 0.583, p = 0.002) and MD of the visual field (r = 0.457, p = 0.042) for the pairs of affected eyes, whereas a poor correlation was found in visual acuity of these eyes (r = 0.279, p = 0.176). Peripapillary RNFL thickness following NAION was positively correlated with MD of visual field (r = 0.312, p = 0.043) and negatively correlated with logMAR visual acuity (r = -0.365, p = 0.009). In patients who experience bilateral NAION, the magnitude of RNFL loss is similar in each eye. There is a greater similarity in visual field loss than in visual acuity between the two affected eyes with NAION of the same individual.

Long-term Effect of Panretinal Photocoagulation on Spectral Domain Optical Coherence Tomography Measurements in Diabetic Retinopathy.

PubMed

Lee, Haeng-Jin; Kang, Tae-Seen; Kwak, Baek-Soo; Jo, Young-Joon; Kim, Jung-Yeul

2017-08-01

To evaluate the effects of panretinal photocoagulation on spectral domain optical coherence tomography measurements in diabetic retinopathy by comparing the thicknesses of the central macula, retinal nerve fiber layer, and ganglion cell layer, we used a Cirrus HD OCT® (Carl Zeiss Meditec, Dublin, CA, USA) in normal and diabetic retinopathy cohorts. We analyzed patients who visited our retinal clinic between May 2013 and July 2014. The patients were classified into four groups: normal (Group A), diabetes without diabetic retinopathy (Group B), severe nonproliferative or proliferative diabetic retinopathy (Group C), and at least 3 years after panretinal photocoagulation treatment (Group D). The mean thicknesses of the macula, retinal nerve fiber layer, and ganglion cell layer in each group were compared by measuring a macular cube 512 × 128 scan and an optic disc cube 200 × 200 scan twice. In total, 154 patients were enrolled. The mean thickness of the central macula in groups A to D was 257.2, 256.8, 257.4, and 255.6 µm, respectively, and did not differ significantly. The mean thickness of the RNFL in group A to D was 96.8, 96.5, 97.2, and 92.8 µm, respectively, and was significantly lower in group D (decreased in the inferior, superior, and nasal sectors, but increased in the temporal). The mean thickness of the ganglion cell layer was also significantly lower in group D (A, 84.5 µm; B, 84.4 µm; C, 82.5 µm; D, 78.5 µm). The mean thicknesses of the retinal nerve fiber and ganglion cell layers were decreased significantly in eyes with diabetic eye disease treated with panretinal photocoagulation compared to normal or eyes with diabetic eye disease that had not been laser-treated. Laser treatment might have altered the thickness of the inner layer of the retina, and such changes should be considered in diabetic retinopathy patients after panretinal photocoagulation treatment.

Immunohistochemical study of dental pulp applied with 4-META/MMA-TBB adhesive resin after pulpotomy.

PubMed

Nakamura, M; Inoue, T; Shimono, M

2000-08-01

The purpose of this study was to investigate nerve regeneration and proliferative activity in amputated pulp tissue after the application of 4-META/MMA-TBB adhesive resin (4-META resin). Calcium hydroxide was used as a control material. At 3 days, fibroblast-like cells were positive for proliferating cell nuclear antigen (PCNA) in both 4-META resin- and calcium hydroxide-treated groups and were located mainly within 0.5 mm from the cut surface. Only a few fragmented neurofilament protein (NFP)-positive nerve fibers were observed in this area. At 7 and 14 days, the number of PCNA-positive cells had gradually decreased and regenerated NFP-positive nerve fibers were observed close to the cut surface of the pulp in both groups. At 21 days in the experimental group, several PCNA-positive cells were still found in the area 0.5 mm from the cut surface, and NFP-positive nerve fibers were detected about 0.15-;0.2 mm from the cut surface. In contrast, a dentin bridge was produced under the necrotic layer at 21 days in the control group. PCNA-positive cells were not found underneath the dentin bridge, but NFP-positive nerve fibers had regenerated close to it. These results suggest that although cell differentiation and nerve regeneration are delayed, wound healing occurred even after the application of 4-META resin to exposed pulp surface the same as calcium hydroxide application. Copyright 2000 John Wiley & Sons, Inc.

Relationship between white matter hyperintensities and retinal nerve fiber layer, choroid, and ganglion cell layer thickness in migraine patients.

PubMed

Iyigundogdu, Ilkin; Derle, Eda; Asena, Leyla; Kural, Feride; Kibaroglu, Seda; Ocal, Ruhsen; Akkoyun, Imren; Can, Ufuk

2018-02-01

Aim To compare the relationship between white matter hyperintensities (WMH) on brain magnetic resonance imaging and retinal nerve fiber layer (RNFL), choroid, and ganglion cell layer (GCL) thicknesses in migraine patients and healthy subjects. We also assessed the role of cerebral hypoperfusion in the formation of these WMH lesions. Methods We enrolled 35 migraine patients without WMH, 37 migraine patients with WMH, and 37 healthy control subjects examined in the Neurology outpatient clinic of our tertiary center from May to December 2015. RFNL, choroid, and GCL thicknesses were measured by optic coherence tomography. Results There were no differences in the RFNL, choroid, or GCL thicknesses between migraine patients with and without WMH ( p > 0.05). Choroid layer thicknesses were significantly lower in migraine patients compared to control subjects ( p < 0.05), while there were no differences in RFNL and GCL thicknesses ( p > 0.05). Conclusions The 'only cerebral hypoperfusion' theory was insufficient to explain the pathophysiology of WMH lesions in migraine patients. In addition, the thinning of the choroid thicknesses in migraine patients suggests a potential causative role for cerebral hypoperfusion and decreased perfusion pressure of the choroid layer.

Evaluation of white matter hyperintensities and retinal fiber layer, ganglion cell layer, inner-plexiform layer, and choroidal layer in migraine patients.

PubMed

Tak, Ali Zeynel Abidin; Sengul, Yıldızhan; Bilak, Şemsettin

2018-03-01

The aim of our study is to assess retinal nerve fiber layer (RNFL), the ganglion cell layer (GCL), inner-plexiform layer (IPL), and choroidal layer in migraine patients with white matter lesion (WML) or without WML, using spectral domain optical coherence tomography (OCT). To our study, 77 migraine patients who are diagnosed with migraine in accordance to the International Classification of Headache Disorders (ICHD)-3 beta and 43 healthy control are included. In accordance to cranial MRI, migraine patients are divided into two groups as those who have white matter lesions (39 patients), and those who do not have a lesion (38 patients). OCT was performed for participants. The average age of participants was comparable. The RNFL average thickness parameter in the migraine group was significantly lower than in the control group (p < 0.01). However, no significant difference was detected among those migraine patients who have WML, and those who do not have. No significant difference is detected among all groups in terms of IPL, GCL, and choroidal layer measuring scales. The proofs showing that affected retinal nerve fiber layer are increased in migraine patients. However, it is not known whether this may affect other layers of retina, or whether there is a correlation between affected retinal structures and white matter lesions. In our study, we found thinner RNFL in migraine patients when we compared with controls but IPL, GCL, and choroid layer values were similar between each patient groups and controls. Also, all parameters were similar between patients with WML and without WML. Studies in this regard are required.

Angiographic and structural imaging using high axial resolution fiber-based visible-light OCT

PubMed Central

Pi, Shaohua; Camino, Acner; Zhang, Miao; Cepurna, William; Liu, Gangjun; Huang, David; Morrison, John; Jia, Yali

2017-01-01

Optical coherence tomography using visible-light sources can increase the axial resolution without the need for broader spectral bandwidth. Here, a high-resolution, fiber-based, visible-light optical coherence tomography system is built and used to image normal retina in rats and blood vessels in chicken embryo. In the rat retina, accurate segmentation of retinal layer boundaries and quantification of layer thicknesses are accomplished. Furthermore, three distinct capillary plexuses in the retina and the choriocapillaris are identified and the characteristic pattern of the nerve fiber layer thickness in rats is revealed. In the chicken embryo model, the microvascular network and a venous bifurcation are examined and the ability to identify and segment large vessel walls is demonstrated. PMID:29082087

Evaluation of retinal nerve fiber layer thickness parameters in myopic population using scanning laser polarimetry (GDxVCC).

PubMed

Dada, Tanuj; Aggarwal, A; Bali, S J; Sharma, A; Shah, B M; Angmo, D; Panda, A

2013-01-01

Myopia presents a significant challenge to the ophthalmologist as myopic discs are often large, tilted, with deep cups and have a thinner neuroretinal rim all of which may mimic glaucomatous optic nerve head changes causing an error in diagnosis. To evaluate the retinal fiber layer (RNFL) thickness in low, moderate and high myopia using scanning laser polarimetry with variable corneal compensation (GDxVCC). One hundred eyes of 100 emmetropes, 30 eyes of low myopes (0 to - 4 D spherical equivalent(SE), 45 eyes with moderate myopia (- 4 to - 8D SE), and 30 eyes with high myopia (- 8 to - 15D SE) were subjected to retinal nerve fiber layer assessment using the scanning laser polarimetry (GDxVCC) in all subjects using the standard protocol. Subjects with IOP > 21 mm Hg, optic nerve head or visual field changes suggestive of glaucoma were excluded from the study. The major outcome parameters were temporal-superior-nasal-inferiortemporal (TSNIT) average, the superior and inferior average and the nerve fibre indicator (NFI). The TSNIT average (p = 0.009), superior (p = 0.001) and inferior average (p = 0.008) were significantly lower; the NFI was higher (P less than 0.001) in moderate myopes as compared to that in emmetropes. In high myopia the RNFL showed supranormal values; the TSNIT average, superior and inferior average was significantly higher(p less than 0.001) as compared to that in emmetropes. The RNFL measurements on scanning laser polarimetry are affected by the myopic refractive error. Moderate myopes show a significant thinning of the RNFL. In high myopia due to peripapillary chorioretinal atrophy and contribution of scleral birefringence, the RNFL values are abnormally high. These findings need to be taken into account while assessing and monitoring glaucoma damage in moderate to high myopes on GDxVCC. © NEPjOPH.

Analysis of Visual Appearance of Retinal Nerve Fibers in High Resolution Fundus Images: A Study on Normal Subjects

PubMed Central

Tornow, Ralf P.; Odstrcilik, Jan; Mayer, Markus A.; Gazarek, Jiri; Jan, Jiri; Kubena, Tomas; Cernosek, Pavel

2013-01-01

The retinal ganglion axons are an important part of the visual system, which can be directly observed by fundus camera. The layer they form together inside the retina is the retinal nerve fiber layer (RNFL). This paper describes results of a texture RNFL analysis in color fundus photographs and compares these results with quantitative measurement of RNFL thickness obtained from optical coherence tomography on normal subjects. It is shown that local mean value, standard deviation, and Shannon entropy extracted from the green and blue channel of fundus images are correlated with corresponding RNFL thickness. The linear correlation coefficients achieved values 0.694, 0.547, and 0.512 for respective features measured on 439 retinal positions in the peripapillary area from 23 eyes of 15 different normal subjects. PMID:24454526

Analysis of visual appearance of retinal nerve fibers in high resolution fundus images: a study on normal subjects.

PubMed

Kolar, Radim; Tornow, Ralf P; Laemmer, Robert; Odstrcilik, Jan; Mayer, Markus A; Gazarek, Jiri; Jan, Jiri; Kubena, Tomas; Cernosek, Pavel

2013-01-01

The retinal ganglion axons are an important part of the visual system, which can be directly observed by fundus camera. The layer they form together inside the retina is the retinal nerve fiber layer (RNFL). This paper describes results of a texture RNFL analysis in color fundus photographs and compares these results with quantitative measurement of RNFL thickness obtained from optical coherence tomography on normal subjects. It is shown that local mean value, standard deviation, and Shannon entropy extracted from the green and blue channel of fundus images are correlated with corresponding RNFL thickness. The linear correlation coefficients achieved values 0.694, 0.547, and 0.512 for respective features measured on 439 retinal positions in the peripapillary area from 23 eyes of 15 different normal subjects.

[Geniculate hemianopia. Diagnostic importance of retinal nerve fiber layer analysis using optical coherence tomography: case report].

PubMed

Moura, Frederico Castelo; Lunardelli, Patrícia; Leite, Cláudia Costa; Monteiro, Mário Luiz Ribeiro

2005-01-01

Lesions of the lateral geniculate body (LGB) are the most unusual lesions of the visual pathways. Imaging studies are very important in establishing the correct diagnosis. However, due to its small size and particular location, the lateral geniculate body and its lesions are sometimes difficult to detect in imaging studies possibly causing diagnostic confusion. The purpose of this paper is to document an unusual case of a lesion of the lateral geniculate body for which an optical coherence tomography study was very important in confirming the anatomic diagnosis of a lateral geniculate body lesion. A 39-year-old woman with a previous diagnosis of uveitis and central nervous system vasculitis was referred for investigation of a right temporal quadrantanopia. She had already been submitted to a magnetic resonance imaging (MRI) that did not show any lesion along the visual pathway. Ophthalmoscopy revealed retinal nerve fiber layer (RNFL) loss that was confirmed by optical coherence tomography. Such finding associated with the observations on the neurological examination strongly suggested a lateral geniculate body lesion. The patient was submitted to another new magnetic resonance imaging obtained with especially oriented thin sections and an ischemic lesion of the lateral geniculate body was observed establishing the correct diagnosis. This case serves to confirm the importance of optical coherence tomography in determining the pattern of retinal nerve fiber layer loss in neuro-ophthalmic diseases and therefore to help in locating a lesion along the visual pathway.

High-resolution imaging of the retinal nerve fiber layer in normal eyes using adaptive optics scanning laser ophthalmoscopy.

PubMed

Takayama, Kohei; Ooto, Sotaro; Hangai, Masanori; Arakawa, Naoko; Oshima, Susumu; Shibata, Naohisa; Hanebuchi, Masaaki; Inoue, Takashi; Yoshimura, Nagahisa

2012-01-01

To conduct high-resolution imaging of the retinal nerve fiber layer (RNFL) in normal eyes using adaptive optics scanning laser ophthalmoscopy (AO-SLO). AO-SLO images were obtained in 20 normal eyes at multiple locations in the posterior polar area and a circular path with a 3-4-mm diameter around the optic disc. For each eye, images focused on the RNFL were recorded and a montage of AO-SLO images was created. AO-SLO images for all eyes showed many hyperreflective bundles in the RNFL. Hyperreflective bundles above or below the fovea were seen in an arch from the temporal periphery on either side of a horizontal dividing line to the optic disc. The dark lines among the hyperreflective bundles were narrower around the optic disc compared with those in the temporal raphe. The hyperreflective bundles corresponded with the direction of the striations on SLO red-free images. The resolution and contrast of the bundles were much higher in AO-SLO images than in red-free fundus photography or SLO red-free images. The mean hyperreflective bundle width around the optic disc had a double-humped shape; the bundles at the temporal and nasal sides of the optic disc were narrower than those above and below the optic disc (P<0.001). RNFL thickness obtained by optical coherence tomography correlated with the hyperreflective bundle widths on AO-SLO (P<0.001) AO-SLO revealed hyperreflective bundles and dark lines in the RNFL, believed to be retinal nerve fiber bundles and Müller cell septa. The widths of the nerve fiber bundles appear to be proportional to the RNFL thickness at equivalent distances from the optic disc.

[Glaucoma and optic nerve drusen: Limitations of optic nerve head OCT].

PubMed

Poli, M; Colange, J; Goutagny, B; Sellem, E

2017-09-01

Optic nerve head drusen are congenital calcium deposits located in the prelaminar section of the optic nerve head. Their association with visual field defects has been classically described, but the diagnosis of glaucoma is not easy in these cases of altered optic nerve head anatomy. We describe the case of a 67-year-old man with optic nerve head drusen complicated by glaucoma, which was confirmed by visual field and OCT examination of the peripapillary retinal nerve fiber layer (RNFL), but the measurement of the minimum distance between the Bruch membrane opening and the internal limiting membrane (minimum rim width, BMO-MRW) by OCT was normal. OCT of the BMO-MRW is a new diagnostic tool for glaucoma. Superficial optic nerve head drusen, which are found between the internal limiting membrane and the Bruch's membrane opening, overestimate the value of this parameter. BMO-MRW measurement is not adapted to cases of optic nerve head drusen and can cause false-negative results for this parameter, and the diagnosis of glaucoma in this case should be based on other parameters such as the presence of a fascicular defect in the retinal nerve fibers, RNFL or macular ganglion cell complex thinning, as well as visual field data. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Estimating a structural bottle neck for eye-brain transfer of visual information from 3D-volumes of the optic nerve head from a commercial OCT device

NASA Astrophysics Data System (ADS)

Malmberg, Filip; Sandberg-Melin, Camilla; Söderberg, Per G.

2016-03-01

The aim of this project was to investigate the possibility of using OCT optic nerve head 3D information captured with a Topcon OCT 2000 device for detection of the shortest distance between the inner limit of the retina and the central limit of the pigment epithelium around the circumference of the optic nerve head. The shortest distance between these boundaries reflects the nerve fiber layer thickness and measurement of this distance is interesting for follow-up of glaucoma.

Detection of retinal nerve fiber layer defects on retinal fundus images for early diagnosis of glaucoma

NASA Astrophysics Data System (ADS)

Muramatsu, Chisako; Hayashi, Yoshinori; Sawada, Akira; Hatanaka, Yuji; Hara, Takeshi; Yamamoto, Tetsuya; Fujita, Hiroshi

2010-01-01

Retinal nerve fiber layer defect (NFLD) is a major sign of glaucoma, which is the second leading cause of blindness in the world. Early detection of NFLDs is critical for improved prognosis of this progressive, blinding disease. We have investigated a computerized scheme for detection of NFLDs on retinal fundus images. In this study, 162 images, including 81 images with 99 NFLDs, were used. After major blood vessels were removed, the images were transformed so that the curved paths of retinal nerves become approximately straight on the basis of ellipses, and the Gabor filters were applied for enhancement of NFLDs. Bandlike regions darker than the surrounding pixels were detected as candidates of NFLDs. For each candidate, image features were determined and the likelihood of a true NFLD was determined by using the linear discriminant analysis and an artificial neural network (ANN). The sensitivity for detecting the NFLDs was 91% at 1.0 false positive per image by using the ANN. The proposed computerized system for the detection of NFLDs can be useful to physicians in the diagnosis of glaucoma in a mass screening.

Anterograde Tracing Method using DiI to Label Vagal Innervation of the Embryonic and Early Postnatal Mouse Gastrointestinal Tract

PubMed Central

Murphy, Michelle C.; Fox, Edward A.

2007-01-01

The mouse is an extremely valuable model for studying vagal development in relation to strain differences, genetic variation, gene manipulations, or pharmacological manipulations. Therefore, a method using 1, 1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) was developed for labeling vagal innervation of the gastrointestinal (GI) tract in embryonic and postnatal mice. DiI labeling was adapted and optimized for this purpose by varying several facets of the method. For example, insertion and crushing of DiI crystals into the nerve led to faster DiI diffusion along vagal axons and diffusion over longer distances as compared with piercing the nerve with a micropipette tip coated with dried DiI oil. Moreover, inclusion of EDTA in the fixative reduced leakage of DiI out of nerve fibers that occurred with long incubations. Also, mounting labeled tissue in PBS was superior to glycerol with n-propyl gallate, which resulted in reduced clarity of DiI labeling that may have been due to DiI leaking out of fibers. Optical sectioning of flattened wholemounts permitted examination of individual tissue layers of the GI tract wall. This procedure aided identification of nerve ending types because in most instances each type innervates a different tissue layer. Between embryonic day 12.5 and postnatal day 8, growth of axons into the GI tract, formation and patterning of fiber bundles in the myenteric plexus and early formation of putative afferent and efferent nerve terminals were observed. Thus, the DiI tracing method developed here has opened up a window for investigation during an important phase of vagal development. PMID:17418900

Relating retinal nerve fiber thickness to behavioral sensitivity in patients with glaucoma: application of a linear model.

PubMed

Hood, Donald C

2007-05-01

Glaucoma causes damage to the retinal ganglion cells and their axons, and this damage can be detected with both structural and functional tests. The purpose of this study was to better understand the relationship between a structural measure of retinal nerve fiber layer (RNFL) and the most common functional test, behavioral sensitivity with static automated perimetry (SAP). First, a linear model, previously shown to describe the relationship between local visual evoked potentials and SAP sensitivity, was modified to predict the change in RNFL as measured by optical coherence tomography. Second, previous work by others was shown to be consistent with this model.

Multifocal visual evoked potentials for early glaucoma detection.

PubMed

Weizer, Jennifer S; Musch, David C; Niziol, Leslie M; Khan, Naheed W

2012-07-01

To compare multifocal visual evoked potentials (mfVEP) with other detection methods in early open-angle glaucoma. Ten patients with suspected glaucoma and 5 with early open-angle glaucoma underwent mfVEP, standard automated perimetry (SAP), short-wave automated perimetry, frequency-doubling technology perimetry, and nerve fiber layer optical coherence tomography. Nineteen healthy control subjects underwent mfVEP and SAP for comparison. Comparisons between groups involving continuous variables were made using independent t tests; for categorical variables, Fisher's exact test was used. Monocular mfVEP cluster defects were associated with an increased SAP pattern standard deviation (P = .0195). Visual fields that showed interocular mfVEP cluster defects were more likely to also show superior quadrant nerve fiber layer thinning by OCT (P = .0152). Multifocal visual evoked potential cluster defects are associated with a functional and an anatomic measure that both relate to glaucomatous optic neuropathy. Copyright 2012, SLACK Incorporated.

VIIP Bedrest Analog Roadmap

NASA Technical Reports Server (NTRS)

Villarreal, Jennifer D.

2014-01-01

The objective is to define successive bed rest campaigns leading to a potential VIIP (Vision Impairment and Intracranial Pressure) countermeasure. To determine if the analog is successful, changes need to occur in the following outcome measures (dependent variables): Intracranial pressure; Retinal nerve fiber layer; Choroidal engorgement; Globe flattening; Axial biometry; Optic nerve sheath diameter distention; Cycloplegic refraction; Visual acuity. Study parameters (independent variables) to include: CO2; Sodium; Exercise (resistive & aerobic); Strict tilt angle.

Comparison of Laser Scanning Diagnostic Devices for Early Glaucoma Detection.

PubMed

Schulze, Andreas; Lamparter, Julia; Pfeiffer, Norbert; Berisha, Fatmire; Schmidtmann, Irene; Hoffmann, Esther M

2015-08-01

To compare the diagnostic accuracy and to evaluate the correlation of optic nerve head and retinal nerve fiber layer thickness values between Fourier-Domain optical coherence tomography (FD-OCT), confocal scanning laser ophthalmoscopy (CSLO), and scanning laser polarimetry (SLP) for early glaucoma detection. Ninety-three patients with early open-angle glaucoma, 58 patients with ocular hypertension, and 60 healthy control subjects were included in this observational, cross-sectional study. All study participants underwent FD-OCT (RTVue-100), CSLO (HRT3), and SLP (GDx VCC) imaging of the optic nerve head and the retinal nerve fiber layer. Area under the receiver operating characteristic curves (AUROC) and Bland-Altman analysis were performed. The parameters with the highest diagnostic accuracy were found for FD-OCT cup-to-disc ratio (AUROC=0.841), for SLP NFI (AUROC=0.835), and for CSLO cup-to-disc ratio (AUROC=0.789). Diagnostic accuracy of the best CSLO and SLP parameter was similar (P=0.259). There was a small statistically significant difference between the best CSLO and FD-OCT parameters for differentiating between glaucoma and healthy eyes (P=0.047). FD-OCT and SLP have a similarly good diagnostic ability to distinguish between early glaucoma and healthy subjects. The diagnostic accuracy of CSLO was comparable with SLP and marginally lower compared with FD-OCT.

Ultrastructural study of relationships between c-kit immunoreactive interstitial cells and other cellular elements in the human colon.

PubMed

Mazzia, C; Porcher, C; Julé, Y; Christen, M O; Henry, M

2000-05-01

C-kit immunocytochemistry was performed on ultrathin sections of human distal colon. Our attention was focused on relationships between c-kit immunoreactive interstitial cells (c-kit ICs) and muscular cells and nervous elements located in the external muscular layers of the colonic wall. C-kit ICs established membrane apposition with both nerve fibers and smooth muscle cells of, respectively, the longitudinal and circular muscle layers, the myenteric area, and the extremus submucosus plexus. C-kit ICs also surrounded the external submucosus plexus and established membrane appositions with nerve elements located inside the myenteric ganglia. These membrane appositions were observed either at the level of the c-kit IC bodies or at that of their cytoplasmic processes. In some cases, membrane appositions were observed concomitantly between the c-kit ICs, nerve fibers, and smooth muscle cells. In all the regions studied, the c-kit ICs were also found to be located in the close vicinity of blood vessels and to have established close contacts with non-immunoreactive fibroblast-like cells. The results of the present study shed essential light on the relationships of c-kit ICs with the neighboring muscle cells and nerve elements, and confirm that the intercalated c-kit ICs well fit with the so-called "interstitial cells of Cajal".

Serosurvey for the Prevalence of Brucella Canis Antibodies in Dogs in Central Ohio

DTIC Science & Technology

1983-01-01

negative urease production ...................... positive indol production ....................... negative1 0 ,58 ,6 2 citrate utilization...retained its spermatogenic ability. The epididymides had ac- cumulations of lymphocytes in the interstitial cell layers ranging from a few cells to large...There was diffuse in- filtration of plasma cells between the inner plexiform layer and the nerve fiber layer of the retina. Some serous exudate and a few

Increased serum level of homocysteine correlates with retinal nerve fiber layer thinning in diabetic retinopathy

PubMed Central

Srivastav, Khushboo; Mahdi, Abbas A.; Shukla, Rajendra K.; Meyer, Carsten H.; Akduman, Levent; Khanna, Vinay K.

2016-01-01

Purpose To study the correlation between serum levels of vitamin B12, folic acid, and homocysteine and the severity of diabetic retinopathy and the correlation with retinal nerve fiber layer (RNFL) thinning on spectral domain optical coherence tomography (SD-OCT). Methods In a tertiary care center–based prospective cross-sectional study, 60 consecutive cases and 20 healthy controls in the age group of 40–65 years were included. The eyes of the cases were divided into three groups according to Early Treatment Diabetic Retinopathy Study (ETDRS) classification: diabetes mellitus without retinopathy (n = 20), non-proliferative diabetic retinopathy with macular edema (n = 20), and proliferative diabetic retinopathy with macular edema (n = 20). The serum levels of vitamin B12 and folic acid were measured using a standard protocol. The serum homocysteine assay was performed using an enzyme-linked immunosorbent assay (ELISA) kit. Average RNFL thickness was measured using SD-OCT. Statistical analysis was used to assess the correlations between the study variables. Results Increased severity of diabetic retinopathy was found to correlate with an increase in the serum levels of homocysteine (F = 53.79; p<0.001). The mean serum levels of vitamin B12 and folic acid were found to be within the normal reference range. A positive correlation was found between retinal nerve fiber layer thinning and serum levels of homocysteine (p<0.001). Conclusions This study, for the first time, demonstrated a correlation between increased homocysteine with a decrease in RNFL thickness and increased severity of diabetic retinopathy. PMID:27994434

Population-based evaluation of retinal nerve fiber layer, retinal ganglion cell layer, and inner plexiform layer as a diagnostic tool for glaucoma.

PubMed

Springelkamp, Henriët; Lee, Kyungmoo; Wolfs, Roger C W; Buitendijk, Gabriëlle H S; Ramdas, Wishal D; Hofman, Albert; Vingerling, Johannes R; Klaver, Caroline C W; Abràmoff, Michael D; Jansonius, Nomdo M

2014-11-20

We determined the glaucoma screening performance of regional optical coherence tomography (OCT) layer thickness measurements in the peripapillary and macular region, in a population-based setting. Subjects (n = 1224) in the Rotterdam Study underwent visual field testing (Humphrey Field Analyzer) and OCT of the macula and optic nerve head (Topcon 3-D OCT-1000). We determined the mean thicknesses of the retinal nerve fiber layer (RNFL), retinal ganglion cell layer (RGCL), and inner plexiform layer for regions-of-interest; thus, defining a series of OCT parameters, using the Iowa Reference Algorithms. Reference standard was the presence of glaucomatous visual field loss (GVFL); controls were subjects without GVFL, an intraocular pressure (IOP) of 21 mm Hg or less, and no positive family history for glaucoma. We calculated the area under the receiver operating characteristics curve (AUCs) and the sensitivity at 97.5% specificity for each parameter. After excluding 23 subjects with an IOP > 21 mm Hg and 73 subjects with a positive family history for glaucoma, there were 1087 controls and 41 glaucoma cases. Mean RGCL thickness in the inferior half of the macular region showed the highest AUC (0.85; 95% confidence interval [CI] 0.77-0.92) and sensitivity (53.7%; 95% CI, 38.7-68.0%). The mean thickness of the peripapillary RNFL had an AUC of 0.77 (95% CI, 0.69-0.85) and a sensitivity of 24.4% (95% CI, 13.7-39.5%). Macular RGCL loss is at least as common as peripapillary RNFL abnormalities in population-based glaucoma cases. Screening for glaucoma using OCT-derived regional thickness identifies approximately half of those cases of glaucoma as diagnosed by perimetry. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Optical coherence tomography, scanning laser polarimetry and confocal scanning laser ophthalmoscopy in retinal nerve fiber layer measurements of glaucoma patients.

PubMed

Fanihagh, Farsad; Kremmer, Stephan; Anastassiou, Gerasimos; Schallenberg, Maurice

2015-01-01

To determine the correlations and strength of association between different imaging systems in analyzing the retinal nerve fiber layer (RNFL) of glaucoma patients: optical coherence tomography (OCT), scanning laser polarimetry (SLP) and confocal scanning laser ophthalmoscopy (CSLO). 114 eyes of patients with moderate open angle glaucoma underwent spectral domain OCT (Topcon SD-OCT 2000 and Zeiss Cirrus HD-OCT), SLP (GDx VCC and GDx Pro) and CSLO (Heidelberg Retina Tomograph, HRT 3). Correlation coefficients were calculated between the structural parameters yielded by these examinations. The quantitative relationship between the measured RNFL thickness globally and for the four regions (superior, inferior, nasal, temporal) were evaluated with different regression models for all used imaging systems. The strongest correlation of RNFL measurements was found between devices using the same technology like GDx VCC and GDx Pro as well as Topcon OCT and Cirrus OCT. In glaucoma patients, the strongest associations (R²) were found between RNFL measurements of the two optical coherence tomography devices Topcon OCT and Cirrus OCT (R² = 0.513) and between GDx VCC and GDx Pro (R² = 0.451). The results of the OCTs and GDX Pro also had a strong quantitative relationship (Topcon OCT R² = 0.339 and Cirrus OCT R² = 0.347). GDx VCC and the OCTs showed a mild to moderate association (Topcon OCT R² = 0.207 and Cirrus OCT R² = 0.258). The confocal scanning laser ophthalmoscopy (HRT 3) had the lowest association to all other devices (Topcon OCT R² = 0.254, Cirrus OCT R² = 0.158, GDx Pro R² = 0.086 and GDx VCC R² = 0.1). The measurements of the RNFL in glaucoma patients reveal a high correlation of OCT and GDx devices because OCTs can measure all major retinal layers and SLP can detect nerve fibers allowing a comparison between the results of this devices. However, CSLO by means of HRT topography can only measure height values of the retinal surface but it cannot distinguish between different retinal layers. This may explain the rather poor correlations and associations between CSLO measurements and those of all other imaging devices which makes it difficult to compare HRT 3 nerve fiber data. These correlations are important in clinical routine especially when different techniques are used in the follow-up of glaucoma patients.

Searching for neurodegeneration in multiple sclerosis at clinical onset: Diagnostic value of biomarkers.

PubMed

Novakova, Lenka; Axelsson, Markus; Malmeström, Clas; Imberg, Henrik; Elias, Olle; Zetterberg, Henrik; Nerman, Olle; Lycke, Jan

2018-01-01

Neurodegeneration occurs during the early stages of multiple sclerosis. It is an essential, devastating part of the pathophysiology. Tools for measuring the degree of neurodegeneration could improve diagnostics and patient characterization. This study aimed to determine the diagnostic value of biomarkers of degeneration in patients with recent clinical onset of suspected multiple sclerosis, and to evaluate these biomarkers for characterizing disease course. This cross-sectional study included 271 patients with clinical features of suspected multiple sclerosis onset and was the baseline of a prospective study. After diagnostic investigations, the patients were classified into the following disease groups: patients with clinically isolated syndrome (n = 4) or early relapsing remitting multiple sclerosis (early RRMS; n = 93); patients with relapsing remitting multiple sclerosis with disease durations ≥2 years (established RRMS; n = 39); patients without multiple sclerosis, but showing symptoms (symptomatic controls; n = 89); and patients diagnosed with other diseases (n = 46). In addition, we included healthy controls (n = 51) and patients with progressive multiple sclerosis (n = 23). We analyzed six biomarkers of neurodegeneration: cerebrospinal fluid neurofilament light chain levels; cerebral spinal fluid glial fibrillary acidic protein; cerebral spinal fluid tau; retinal nerve fiber layer thickness; macula volume; and the brain parenchymal fraction. Except for increased cerebral spinal fluid neurofilament light chain levels, median 670 ng/L (IQR 400-2110), we could not find signs of early degeneration in the early disease group with recent clinical onset. However, the intrathecal immunoglobin G production and cerebral spinal fluid neurofilament light chain levels showed diagnostic value. Moreover, elevated levels of cerebral spinal fluid glial fibrillary acidic protein, thin retinal nerve fiber layers, and low brain parenchymal fractions were associated with progressive disease, but not with the other phenotypes. Thin retinal nerve fiber layers and low brain parenchymal fractions, which indicated neurodegeneration, were associated with longer disease duration. In clinically suspected multiple sclerosis, intrathecal immunoglobin G production and neurofilament light chain levels had diagnostic value. Therefore, these biomarkers could be included in diagnostic work-ups for multiple sclerosis. We found that the thickness of the retinal nerve fiber layer and the brain parenchymal fraction were not different between individuals that were healthy, symptomatic, or newly diagnosed with multiple sclerosis. This finding suggested that neurodegeneration had not reached a significant magnitude in patients with a recent clinical onset of multiple sclerosis.

Repeatability and Reproducibility of Retinal Nerve Fiber Layer Parameters Measured by Scanning Laser Polarimetry with Enhanced Corneal Compensation in Normal and Glaucomatous Eyes.

PubMed

Ara, Mirian; Ferreras, Antonio; Pajarin, Ana B; Calvo, Pilar; Figus, Michele; Frezzotti, Paolo

2015-01-01

To assess the intrasession repeatability and intersession reproducibility of peripapillary retinal nerve fiber layer (RNFL) thickness parameters measured by scanning laser polarimetry (SLP) with enhanced corneal compensation (ECC) in healthy and glaucomatous eyes. One randomly selected eye of 82 healthy individuals and 60 glaucoma subjects was evaluated. Three scans were acquired during the first visit to evaluate intravisit repeatability. A different operator obtained two additional scans within 2 months after the first session to determine intervisit reproducibility. The intraclass correlation coefficient (ICC), coefficient of variation (COV), and test-retest variability (TRT) were calculated for all SLP parameters in both groups. ICCs ranged from 0.920 to 0.982 for intravisit measurements and from 0.910 to 0.978 for intervisit measurements. The temporal-superior-nasal-inferior-temporal (TSNIT) average was the highest (0.967 and 0.946) in normal eyes, while nerve fiber indicator (NFI; 0.982) and inferior average (0.978) yielded the best ICC in glaucomatous eyes for intravisit and intervisit measurements, respectively. All COVs were under 10% in both groups, except NFI. TSNIT average had the lowest COV (2.43%) in either type of measurement. Intervisit TRT ranged from 6.48 to 12.84. The reproducibility of peripapillary RNFL measurements obtained with SLP-ECC was excellent, indicating that SLP-ECC is sufficiently accurate for monitoring glaucoma progression.

Effect of race, age, and axial length on optic nerve head parameters and retinal nerve fiber layer thickness measured by Cirrus HD-OCT.

PubMed

Knight, O'Rese J; Girkin, Christopher A; Budenz, Donald L; Durbin, Mary K; Feuer, William J

2012-03-01

To determine the effect of race, demographic, and ocular variables on optic nerve head and retinal nerve fiber layer (RNFL) thickness measurements using spectral-domain optical coherence tomography. In a cross-sectional observational study, 284 normal subjects aged 18 to 84 years were evaluated at 7 sites using Cirrus HD-OCT. Disc area, rim area, average cup-disc ratio, vertical cup-disc ratio, cup volume, and average, temporal, superior, nasal, and inferior RNFL thicknesses were calculated. The main outcome measures were associations between Cirrus HD-OCT optic nerve head and RNFL measurements and age, sex, and race. The 284 subjects self-identified as being of European (122), Chinese (63), African (51), or Hispanic (35) descent. After adjusting for the effect of age, there was a statistically significant difference among racial groups for all optic nerve head and RNFL parameters (all P ≤ .005) except rim area (P = .22). Rim area, average cup-disc ratio, vertical cup-disc ratio, and cup volume were moderately associated with disc area (r(2) = 0.15, 0.33, 0.33, and 0.37, respectively). After a linear adjustment for disc area, there was no statistically significant difference among racial groups for any optic nerve head parameter. Individuals of European descent had thinner RNFL measurements except in the temporal quadrant. There are racial differences in optic disc area, average cup-disc ratio, vertical cup-disc ratio, cup volume, and RNFL thickness as measured by Cirrus HD-OCT. These differences should be considered when using Cirrus HD-OCT to assess for glaucomatous damage in differing population groups.

Effect of Race, Age, and Axial Length on Optic Nerve Head Parameters and Retinal Nerve Fiber Layer Thickness Measured by Cirrus HD-OCT

PubMed Central

Knight, O’Rese J.; Girkin, Christopher A.; Budenz, Donald L.; Durbin, Mary K.; Feuer, William J.

2017-01-01

Objective To determine the effect of race, demographic, and ocular variables on optic nerve head and retinal nerve fiber layer (RNFL) thickness measurements using spectral-domain optical coherence tomography. Methods In a cross-sectional observational study, 284 normal subjects aged 18 to 84 years were evaluated at 7 sites using Cirrus HD-OCT. Disc area, rim area, average cup-disc ratio, vertical cup-disc ratio, cup volume, and average, temporal, superior, nasal, and inferior RNFL thicknesses were calculated. The main outcome measures were associations between Cirrus HD-OCT optic nerve head and RNFL measurements and age, sex, and race. Results The 284 subjects self-identified as being of European (122), Chinese (63), African (51), or Hispanic (35) descent. After adjusting for the effect of age, there was a statistically significant difference among racial groups for all optic nerve head and RNFL parameters (all P≤.005) except rim area (P=.22). Rim area, average cup-disc ratio, vertical cup-disc ratio, and cup volume were moderately associated with disc area (r2=0.15, 0.33, 0.33, and 0.37, respectively). After a linear adjustment for disc area, there was no statistically significant difference among racial groups for any optic nerve head parameter. Individuals of European descent had thinner RNFL measurements except in the temporal quadrant. Conclusions There are racial differences in optic disc area, average cup-disc ratio, vertical cup-disc ratio, cup volume, and RNFL thickness as measured by Cirrus HD-OCT. These differences should be considered when using Cirrus HD-OCT to assess for glaucomatous damage in differing population groups. PMID:22411660

Combined use of Doppler OCT and en face OCT functions for discrimination of an aneurysm in the lamina cribrosa from a disc hemorrhage.

PubMed

Holló, Gábor

2015-12-01

In addition to retinal nerve fiber layer thickness measurements, the recently introduced AngioVue optical coherence tomography (OCT) offers corresponding layer-by-layer Doppler OCT and en face OCT functions, for simultaneous evaluation of perfusion and structure of the optic nerve head. We investigated the clinical usefulness of combined use of Doppler and en face Fourier-domain OCT functions of the AngioVue Fourier-domain OCT for discrimination of a disc hemorrhage and a disc hemorrhage-like atypical vessel structure located deep in the lamina cribrosa. We present our findings with AngioVue OCT on a disc hemorrhage and a spatially related retinal nerve fiber layer bundle defect in a glaucomatous eye (case 1). Both alterations were detected on en face OCT images without any Doppler OCT signal. We also report on an aneurysm suggestive for a disc hemorrhage on clinical examination and disc photography in a treated ocular hypertensive eye (case 2). The aneurysm was within the lamina cribrosa tissue at the border of the cup and the neuroretinal rim. This vascular structure produced strong Doppler signals but no structurally detectable signs on the en face OCT images. Combined evaluation of corresponding Doppler OCT and en face OCT images enables ophthalmologists to easily separate true disc hemorrhages from disc hemorrhage-like deep vascular structures. This is of clinical significance in preventing unnecessary intensification of pressure-lowering treatment in glaucoma.

Optical stimulation of the prostate nerves: A potential diagnostic technique

NASA Astrophysics Data System (ADS)

Tozburun, Serhat

There is wide variability in sexual potency rates (9--86%) after nerve-sparing prostate cancer surgery due to limited knowledge of the location of the cavernous nerves (CN's) on the prostate surface, which are responsible for erectile function. Thus, preservation of the CN's is critical in preserving a man's ability to have spontaneous erections following surgery. Nerve-mapping devices, utilizing conventional Electrical Nerve Stimulation (ENS) techniques, have been used as intra-operative diagnostic tools to assist in preservation of the CN. However, these technologies have proven inconsistent and unreliable in identifying the CN's due to the need for physical contact, the lack of spatial selectivity, and the presence of electrical artifacts in measurements. Optical Nerve Stimulation (ONS), using pulsed infrared laser radiation, is studied as an alternative to ENS. The objective of this study is sevenfold: (1) to develop a laparoscopic laser probe for ONS of the CN's in a rat model, in vivo; (2) to demonstrate faster ONS using continuous-wave infrared laser radiation; (3) to describe and characterize the mechanism of successful ONS using alternative laser wavelengths; (4) to test a compact, inexpensive all-single-mode fiber configuration for optical stimulation of the rat CN studies; (5) to implement fiber optic beam shaping methods for comparison of Gaussian and flat-top spatial beam profiles during ONS; (6) to demonstrate successful ONS of CN's through a thin layer of fascia placed over the nerve and prostate gland; and (7) to verify the experimentally determined therapeutic window for safe and reliable ONS without thermal damage to the CN's by comparison with a computational model for thermal damage. A 5.5-Watt Thulium fiber laser operated at 1870 nm and two pigtailed, single mode, near-IR diode lasers (150-mW, 1455-nm laser and 500-mW, 1550-nm laser) were used for non-contact stimulation of the rat CN's. Successful laser stimulation, as measured by an intracavernous pressure (ICP) response in the penis, was achieved with the laser operating in CW mode. CW optical nerve stimulation provides a significantly faster ICP response time using a lower laser power laser than conventional pulsed stimulation. An all-single-mode fiber design was successfully tested in a rat model. The CN reached a threshold temperature of ˜ 42 °C, with response times as short as 3 s, and ICP responses in the rat penis of up to 50 mmHg compared to a baseline of 5--10 mmHg. Chemical etching of the distal single-mode-fiber tip produced a concave shape and transformed the Gaussian to a flat-top spatial beam profile, resulting in simplified alignment of the laser beam with the nerve. This novel, all-single-mode-fiber laser nerve stimulation system introduces several advantages including: (1) a less expensive and more compact ONS configuration; (2) elimination of alignment and cleaning bulk optical components; and (3) improved spatial beam profile for simplified alignment. For the fascia layers over the CN's (240--600 microm), the 1550 nm laser with an optical penetration depth of ˜ 930 microm in water was substituted for the 1455 nm laser. Successful ONS was achieved, for the first time, in fascia layers up to 450 microm thick which is critical for future clinical translation of this method for intra-operative identification and preservation of CN's during prostate cancer surgery. In order to define the upper limit of the therapeutic window for ONS of CN in a rat model, in vivo, identification of the thermal damage threshold for the CN after laser irradiation was investigated by direct comparison of the visible thermal damage data with a theoretical thermal damage calculation utilizing a standard Arrhenius integral model.

Bidirectional synaptic plasticity in the cerebellum-like mammalian dorsal cochlear nucleus

NASA Astrophysics Data System (ADS)

Fujino, Kiyohiro; Oertel, Donata

2003-01-01

The dorsal cochlear nucleus integrates acoustic with multimodal sensory inputs from widespread areas of the brain. Multimodal inputs are brought to spiny dendrites of fusiform and cartwheel cells in the molecular layer by parallel fibers through synapses that are subject to long-term potentiation and long-term depression. Acoustic cues are brought to smooth dendrites of fusiform cells in the deep layer by auditory nerve fibers through synapses that do not show plasticity. Plasticity requires Ca2+-induced Ca2+ release; its sensitivity to antagonists of N-methyl-D-aspartate and metabotropic glutamate receptors differs in fusiform and cartwheel cells.

Label-free photoacoustic microscopy of peripheral nerves

NASA Astrophysics Data System (ADS)

Matthews, Thomas Paul; Zhang, Chi; Yao, Da-Kang; Maslov, Konstantin; Wang, Lihong V.

2014-01-01

Peripheral neuropathy is a common neurological problem that affects millions of people worldwide. Diagnosis and treatment of this condition are often hindered by the difficulties in making objective, noninvasive measurements of nerve fibers. Photoacoustic microscopy (PAM) has the ability to obtain high resolution, specific images of peripheral nerves without exogenous contrast. We demonstrated the first proof-of-concept imaging of peripheral nerves using PAM. As validated by both standard histology and photoacoustic spectroscopy, the origin of photoacoustic signals is myelin, the primary source of lipids in the nerves. An extracted sciatic nerve sandwiched between two layers of chicken tissue was imaged by PAM to mimic the in vivo case. Ordered fibrous structures inside the nerve, caused by the bundles of myelin-coated axons, could be observed clearly. With further technical improvements, PAM can potentially be applied to monitor and diagnose peripheral neuropathies.

Anatomical feasibility of vagus nerve esophageal branch transfer to the phrenic nerve☆

PubMed Central

Wang, Ce; Liu, Jun; Yuan, Wen; Zhou, Xuhui; Wang, Xinwei; Xu, Peng; Chen, Jian; Wu, Guoxin; Shi, Sheng

2012-01-01

This study measured the vagus and phrenic nerves from 12 adult cadavers. We found that the width and thickness of the vagus and phrenic nerves were different in the chest. The distance from the point of the vagus nerve and phrenic nerve on the plane of the inferior border of portal pulmonary arteries (T point) was approximately 7 cm to the diaphragm and was approximately 10 cm to the clavicle level. The number of motor fibers in the vagus nerves was 1 716 ± 362, and the number of nerve fibers was 4 473 ± 653. The number of motor fibers in the phrenic nerves ranged from 3 078 ± 684 to 4 794 ± 638, and the number of nerve fibers ranged from 3 437 ± 642 to 5 071 ± 723. No significant difference was found in the total number of nerve fibers. The results suggest that width, thickness, and total number of nerve fibers are similar between the vagus and phrenic nerves, but the number of motor fibers is different between them. PMID:25745467

Analysis of macular and nerve fiber layer thickness in multiple sclerosis patients according to severity level and optic neuritis episodes.

PubMed

Soler García, A; Padilla Parrado, F; Figueroa-Ortiz, L C; González Gómez, A; García-Ben, A; García-Ben, E; García-Campos, J M

2016-01-01

Quantitative assessment of macular and nerve fibre layer thickness in multiple sclerosis patients with regard to expanded disability status scale (EDSS) and presence or absence of previous optic neuritis episodes. We recruited 62 patients with multiple sclerosis (53 relapsing-remitting and 9 secondary progressive) and 12 disease-free controls. All patients underwent an ophthalmological examination, including quantitative analysis of the nerve fibre layer and macular thickness using optical coherence tomography. Patients were classified according to EDSS as A (lower than 1.5), B (between 1.5 and 3.5), and C (above 3.5). Mean nerve fibre layer thickness in control, A, B, and C groups was 103.35±12.62, 99.04±14.35, 93.59±15.41, and 87.36±18.75μm respectively, with statistically significant differences (P<.05). In patients with no history of optic neuritis, history of episodes in the last 3 to 6 months, or history longer than 6 months, mean nerve fibre layer thickness was 99.25±13.71, 93.92±13.30 and 80.07±15.91μm respectively; differences were significant (P<.05). Mean macular thickness in control, A, B, and C groups was 220.01±12.07, 217.78±20.02, 217.68±20.77, and 219.04±24.26μm respectively. Differences were not statistically significant. The mean retinal nerve fibre layer thickness in multiple sclerosis patients is related to the EDSS level. Patients with previous optic neuritis episodes have a thinner retinal nerve fibre layer than patients with no history of these episodes. Mean macular thickness is not correlated to EDSS level. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Role of Retinal Nerve Fiber Layer Thickness and Optic Disk Measurement by OCT on Early Diagnosis of Glaucoma.

PubMed

Hua, Zanmei; Fang, Qiuyun; Sha, Xiangyin; Yang, Ruiming; Hong, Zuopeng

2015-03-01

Glaucoma is an eye disease that can lead to irreversible optic nerve damage and cause blindness. Optical coherence tomography (OCT) allows an early diagnosis of glaucoma by the measurements of the retinal nerve fiber and optic disc parameters. A retrospective study was designed to analyze the effects of the measurement of the retinal nerve fiber layer (RNFL) thickness and the optic disc tomography by spectral-domain OCT on the early diagnosis of suspected glaucoma and primary open angle glaucoma (POAG). This was a clinical case-control study. The RNFL thickness around the optic disc and optic disk tomographic parameters of the control (n = 51, 98 eyes), suspected glaucoma (n = 81, 146 eyes), and POAG groups (n = 55, 106 eyes) were measured by OCT. The parameters included superior, inferior, nasal and temporal mean RNFL thickness, disc area (DA), cup area (CA), rim area (RA), disc volume (DV), cup volume (CV), rim volume (RV), cup/disc area ratio (CA/DA), rim/disc area ratio (RA/DA), cup/disc volume ratio (CV/DV) and rim/disc volume ratio (RV/DV). Superior, nasal, and mean RNFL parameters, DA, CA,RA, DV, CV, CA/DA, RA/DA, CV/DV and RV/DV significantly differed among three groups by single-factorial ANOVA. Inferior and temporal RNFL thickness significantly differed between the control and POAG groups. No significant difference was observed in RV among three groups. In the POAG group, the maximum area under the ROC curve (AROC) of mean RNFL thickness was 0.845. The maximum AROC of optic disk parameters was RA/DA (0.998), followed by CA/DA (0.997). The AROC of CA, RA, CV, and DV were all > 0.900. OCT may serve as a useful diagnostic modality in distinguishing suspected glaucoma from POAG.

Corneal Confocal Microscopy Detects Corneal Nerve Damage in Patients Admitted With Acute Ischemic Stroke.

PubMed

Khan, Adnan; Akhtar, Naveed; Kamran, Saadat; Ponirakis, Georgios; Petropoulos, Ioannis N; Tunio, Nahel A; Dargham, Soha R; Imam, Yahia; Sartaj, Faheem; Parray, Aijaz; Bourke, Paula; Khan, Rabia; Santos, Mark; Joseph, Sujatha; Shuaib, Ashfaq; Malik, Rayaz A

2017-11-01

Corneal confocal microscopy can identify corneal nerve damage in patients with peripheral and central neurodegeneration. However, the use of corneal confocal microscopy in patients presenting with acute ischemic stroke is unknown. One hundred thirty patients (57 without diabetes mellitus [normal glucose tolerance], 32 with impaired glucose tolerance, and 41 with type 2 diabetes mellitus) admitted with acute ischemic stroke, and 28 age-matched healthy control participants underwent corneal confocal microscopy to quantify corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length. There was a significant reduction in corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length in stroke patients with normal glucose tolerance ( P <0.001, P <0.001, P <0.001), impaired glucose tolerance ( P =0.004, P <0.001, P =0.002), and type 2 diabetes mellitus ( P <0.001, P <0.001, P <0.001) compared with controls. HbA1c and triglycerides correlated with corneal nerve fiber density ( r =-0.187, P =0.03; r =-0.229 P =0.01), corneal nerve fiber length ( r =-0.228, P =0.009; r =-0.285; P =0.001), and corneal nerve branch density ( r =-0.187, P =0.033; r =-0.229, P =0.01). Multiple linear regression showed no independent associations between corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length and relevant risk factors for stroke. Corneal confocal microscopy is a rapid noninvasive ophthalmic imaging technique that identifies corneal nerve fiber loss in patients with acute ischemic stroke. © 2017 American Heart Association, Inc.

Automated detection of retinal nerve fiber layer defects on fundus images: false positive reduction based on vessel likelihood

NASA Astrophysics Data System (ADS)

Muramatsu, Chisako; Ishida, Kyoko; Sawada, Akira; Hatanaka, Yuji; Yamamoto, Tetsuya; Fujita, Hiroshi

2016-03-01

Early detection of glaucoma is important to slow down or cease progression of the disease and for preventing total blindness. We have previously proposed an automated scheme for detection of retinal nerve fiber layer defect (NFLD), which is one of the early signs of glaucoma observed on retinal fundus images. In this study, a new multi-step detection scheme was included to improve detection of subtle and narrow NFLDs. In addition, new features were added to distinguish between NFLDs and blood vessels, which are frequent sites of false positives (FPs). The result was evaluated with a new test dataset consisted of 261 cases, including 130 cases with NFLDs. Using the proposed method, the initial detection rate was improved from 82% to 98%. At the sensitivity of 80%, the number of FPs per image was reduced from 4.25 to 1.36. The result indicates the potential usefulness of the proposed method for early detection of glaucoma.

Laser-induced retinal nerve fiber layer injury in the nonhuman primate

NASA Astrophysics Data System (ADS)

Zwick, Harry; Belkin, Michael; Zuclich, Joseph A.; Lund, David J.; Schuschereba, Steven T.; Scales, David K.

1996-04-01

We have evaluated the acute effects of Argon laser injury to the retinal nerve fiber layer (NFL) in the non-human primate. Single Argon laser exposures of 150 millijoules were employed to induce retinal NFL injury. Retinal NFL injury is not acute; unlike its parallel in retinal disease it has two components that emanate from the acute retinal injury site. The ascending component is more visible, primarily because it is ascending toward the disk, representing ganglion cell axons cut off from their nutrient base, the ganglion cell body; the descending component may require up to 3 weeks to develop. Its characterization depends on the distribution of retinal NFL and the slower degeneration of the ganglion cell bodies. Fluorescein angiography suggest a retinal capillary loss that occurs in the capillary bed of the retinal NFL defect. It may reflect a reduced capillary vascular requirement of the NFL as well as a possible reduction of activity in the axonal transport mechanisms in the ascending NFL defect.

Assessment of Retinal Nerve Fiber Layer Using Optical Coherence Tomography and Scanning Laser Polarimetry in Progressive Glaucomatous Optic Neuropathy

PubMed Central

Sehi, Mitra; Greenfield, David S.

2006-01-01

Purpose To describe a case of progressive glaucomatous optic neuropathy using scanning laser polarimetry with fixed (SLP-FCC) and variable corneal compensation (SLP-VCC) and optical coherence tomography (OCT). Design Observational case report. Methods A 21-year-old male with juvenile primary open-angle glaucoma developed progression because of noncompliance with therapy. The patient underwent dilated stereoscopic examination and photography of the optic disk, standard automated perimetry (SAP), OCT, and SLP imaging with FCC and VCC at the baseline examination and after four years of follow-up. Results Optic disk, retinal nerve fiber layer (RNFL) atrophy, and SAP progression was observed. Reduction in mean RNFL thickness (average, superior, inferior) was 18, 18, and 27 microns (OCT); 22, 40, and 17 microns (SLP-FCC); and 6, 12, and 12 microns (SLP-VCC), respectively. Conclusions This case demonstrates that digital imaging of the peripapillary RNFL is capable of documentation and measurement of progressive glaucomatous RNFL atrophy. PMID:17157591

Progressive Retinal Nerve Fiber Layer Atrophy Associated With Enlarging Peripapillary Pit.

PubMed

Lee, Eun Ji; Kim, Tae-Woo

2017-02-01

To report a case in which progressive retinal nerve fiber layer (RNFL) atrophy was observed along with enlargement of the peripapillary pit. A 34-year-old male was diagnosed with primary open-angle glaucoma and followed up for 4 years with regular ophthalmic examinations. Both eyes were myopic (-10 D, OD and -10.5 D, OS), and untreated intraocular pressures were 18 mm Hg (OD) and 16 mm Hg (OS). A subtle depression of the superotemporal peripapillary area was deepened and emerged as a peripapillary pit during the follow-up period. With the enlargement of the peripapillary pit, a RNFL defect at the location of pit widened and thinned continuously. The enlargement of the pit was documented by the spectral-domain optical coherence tomography posterior pole scanning. Progressive RNFL atrophy was observed with enlargement of the peripapillary pit. The finding suggests that tensile stress derived from the scleral stretching may have significant influence on the integrity of the RNFL.

Comparison between the Correlations of Retinal Nerve Fiber Layer Thickness Measured by Spectral Domain Optical Coherence Tomography and Visual Field Defects in Standard Automated White-on-White Perimetry versus Pulsar Perimetry.

PubMed

Alnawaiseh, Maged; Hömberg, Lisann; Eter, Nicole; Prokosch, Verena

2017-01-01

To compare the structure-function relationships between retinal nerve fiber layer thickness (RNFLT) and visual field defects measured either by standard automated perimetry (SAP) or by Pulsar perimetry (PP). 263 eyes of 143 patients were prospectively included. Depending on the RNFLT, patients were assigned to the glaucoma group (group A: RNFL score 3-6) or the control group (group B: RNFL score 0-2). Structure-function relationships between RNFLT and mean sensitivity (MS) measured by SAP and PP were analyzed. Throughout the entire group, the MS assessed by PP and SAP correlated significantly with RNFLT in all sectors. In the glaucoma group, there was no significant difference between the correlations RNFL-SAP and RNFL-PP, whereas a significant difference was found in the control group. In the control group, the correlation between structure and function based on the PP data was significantly stronger than that based on SAP.

A reinterpretation of certain disorders affecting the eye muscles and their tissues

PubMed Central

Poonyathalang, Anuchit; Khanna, Sangeeta; Leigh, R John

2007-01-01

Recent discoveries about the orbital tissues prompt a re-evaluation of the way that clinicians think about disorders affecting the extraocular muscles, their nerves and motoneurons in the brainstem. The revolutionary discovery that the orbital layers of the extraocular muscles insert not onto the eyeball, but into fibromuscular pulleys that guide the orbital layers, provides explanations for the kinematic properties of eye rotations and clinical findings in some patients with strabismus. The demonstration that all extraocular fibers types, except pale global fibers, lack synaptic folding provides an explanation for why saccades may remain fast in patients with limited ocular mobility due to myasthenia gravis. More than one mechanism may account for the observation that patients with disorders affecting the eye muscles or their nerves can present with the appearance of central disorders of ocular motility, such as internuclear ophthalmoplegia. New approaches to analyzing saccades in patients with disjunctive eye movements provide the means to identify disorders affecting the peripheral or central components of the ocular motor system, or both. PMID:19668518

Cone dysfunctions in retinitis pigmentosa with retinal nerve fiber layer thickening

PubMed Central

Sobacı, Güngör; Özge, Gökhan; Gündoğan, Fatih Ç

2012-01-01

Purpose To investigate whether or not thicker retinal nerve fiber layer (RNFL) in retinitis pigmentosa (RP) patients relates to functional abnormalities of the photoreceptors. Methods Optical coherence tomography-based RNFL thickness was measured by Stratus-3™ (Zeiss, Basel, Switzerland) optical coherence tomography and electroretinogram (ERG) recordings made using the RETI-port® system (Roland, Wiesbaden, Germany) in 27 patients with retinitis pigmentosa and in 30 healthy subjects. Results Photopic ERG b-wave amplitude, cone ERG b-wave latency, 30 Hz flicker amplitude, and 30 Hz flicker latency had significant correlations to the RNFL-temporal (r = −0.55, P = 0.004, r = 0.68, P = 0.001, r = −0.65, P = 0.001, and r = −0.52, P = 0.007, respectively). Eyes with thicker RNFL (ten eyes) differed significantly from those with thinner RNFL (eight eyes) regarding cone ERG b-wave latency values only (P = 0.001). Conclusion Thicker RNFL in patients with retinitis pigmentosa may be associated with functional abnormality of the cone system. PMID:22536039

Cone dysfunctions in retinitis pigmentosa with retinal nerve fiber layer thickening.

PubMed

Sobacı, Güngör; Ozge, Gökhan; Gündoğan, Fatih Ç

2012-01-01

To investigate whether or not thicker retinal nerve fiber layer (RNFL) in retinitis pigmentosa (RP) patients relates to functional abnormalities of the photoreceptors. Optical coherence tomography-based RNFL thickness was measured by Stratus-3™ (Zeiss, Basel, Switzerland) optical coherence tomography and electroretinogram (ERG) recordings made using the RETI-port(®) system (Roland, Wiesbaden, Germany) in 27 patients with retinitis pigmentosa and in 30 healthy subjects. Photopic ERG b-wave amplitude, cone ERG b-wave latency, 30 Hz flicker amplitude, and 30 Hz flicker latency had significant correlations to the RNFL-temporal (r = -0.55, P = 0.004, r = 0.68, P = 0.001, r = -0.65, P = 0.001, and r = -0.52, P = 0.007, respectively). Eyes with thicker RNFL (ten eyes) differed significantly from those with thinner RNFL (eight eyes) regarding cone ERG b-wave latency values only (P = 0.001). Thicker RNFL in patients with retinitis pigmentosa may be associated with functional abnormality of the cone system.

Repeatability and Reproducibility of Retinal Nerve Fiber Layer Parameters Measured by Scanning Laser Polarimetry with Enhanced Corneal Compensation in Normal and Glaucomatous Eyes

PubMed Central

Ara, Mirian; Pajarin, Ana B.

2015-01-01

Objective. To assess the intrasession repeatability and intersession reproducibility of peripapillary retinal nerve fiber layer (RNFL) thickness parameters measured by scanning laser polarimetry (SLP) with enhanced corneal compensation (ECC) in healthy and glaucomatous eyes. Methods. One randomly selected eye of 82 healthy individuals and 60 glaucoma subjects was evaluated. Three scans were acquired during the first visit to evaluate intravisit repeatability. A different operator obtained two additional scans within 2 months after the first session to determine intervisit reproducibility. The intraclass correlation coefficient (ICC), coefficient of variation (COV), and test-retest variability (TRT) were calculated for all SLP parameters in both groups. Results. ICCs ranged from 0.920 to 0.982 for intravisit measurements and from 0.910 to 0.978 for intervisit measurements. The temporal-superior-nasal-inferior-temporal (TSNIT) average was the highest (0.967 and 0.946) in normal eyes, while nerve fiber indicator (NFI; 0.982) and inferior average (0.978) yielded the best ICC in glaucomatous eyes for intravisit and intervisit measurements, respectively. All COVs were under 10% in both groups, except NFI. TSNIT average had the lowest COV (2.43%) in either type of measurement. Intervisit TRT ranged from 6.48 to 12.84. Conclusions. The reproducibility of peripapillary RNFL measurements obtained with SLP-ECC was excellent, indicating that SLP-ECC is sufficiently accurate for monitoring glaucoma progression. PMID:26185762

In-vivo imaging of retinal nerve fiber layer vasculature: imaging - histology comparison

PubMed Central

Scoles, Drew; Gray, Daniel C; Hunter, Jennifer J; Wolfe, Robert; Gee, Bernard P; Geng, Ying; Masella, Benjamin D; Libby, Richard T; Russell, Stephen; Williams, David R; Merigan, William H

2009-01-01

Background Although it has been suggested that alterations of nerve fiber layer vasculature may be involved in the etiology of eye diseases, including glaucoma, it has not been possible to examine this vasculature in-vivo. This report describes a novel imaging method, fluorescence adaptive optics (FAO) scanning laser ophthalmoscopy (SLO), that makes possible for the first time in-vivo imaging of this vasculature in the living macaque, comparing in-vivo and ex-vivo imaging of this vascular bed. Methods We injected sodium fluorescein intravenously in two macaque monkeys while imaging the retina with an FAO-SLO. An argon laser provided the 488 nm excitation source for fluorescence imaging. Reflectance images, obtained simultaneously with near infrared light, permitted precise surface registration of individual frames of the fluorescence imaging. In-vivo imaging was then compared to ex-vivo confocal microscopy of the same tissue. Results Superficial focus (innermost retina) at all depths within the NFL revealed a vasculature with extremely long capillaries, thin walls, little variation in caliber and parallel-linked structure oriented parallel to the NFL axons, typical of the radial peripapillary capillaries (RPCs). However, at a deeper focus beneath the NFL, (toward outer retina) the polygonal pattern typical of the ganglion cell layer (inner) and outer retinal vasculature was seen. These distinguishing patterns were also seen on histological examination of the same retinas. Furthermore, the thickness of the RPC beds and the caliber of individual RPCs determined by imaging closely matched that measured in histological sections. Conclusion This robust method demonstrates in-vivo, high-resolution, confocal imaging of the vasculature through the full thickness of the NFL in the living macaque, in precise agreement with histology. FAO provides a new tool to examine possible primary or secondary role of the nerve fiber layer vasculature in retinal vascular disorders and other eye diseases, such as glaucoma. PMID:19698151

Morphometric analysis of the diameter and g-ratio of the myelinated nerve fibers of the human sciatic nerve during the aging process.

PubMed

Ugrenović, Sladjana; Jovanović, Ivan; Vasović, Ljiljana; Kundalić, Braca; Čukuranović, Rade; Stefanović, Vladisav

2016-06-01

Myelinated nerve fibers suffer from different degrees of atrophy with age. The success of subsequent regeneration varies. The aim of this research was to analyze myelinated fibers of the human sciatic nerve during the aging process. Morphometric analysis was performed on 17 cases with an age range from 9 to 93 years. The outer and inner diameter of 100 randomly selected nerve fibers was measured in each of the cases evaluated, and the g-ratio (axonal diameter/outer diameter of the whole nerve fiber) of each was calculated. Scatter plots of the diameters and g-ratios of the analyzed fibers were then analyzed. Nerve fibers of each case were classified into three groups according to the g-ratio values: group I (g-ratio lower than 0.6), group II (g-ratio from 0.6 to 0.7) and group III (g-ratio higher than 0.7). Afterwards, nerve fibers of group II were further classified into small and large subgroups. The percentages of each group of nerve fibers were computed for each case and these values were used for correlational and bivariate linear regression analysis. The percentage of myelinated nerve fibers with large diameter and optimal g-ratio of the sciatic nerve declines significantly with age. This is accompanied by a simultaneous significant increase in the percentage of small myelinated fibers with g-ratio values close to 1 that occupy the upper left quadrant of the scatter plot. It can be concluded that aging of the sciatic nerve is associated with significant atrophy of large myelinated fibers. Additionally, a significant increase in regenerated nerve fibers with thinner myelin sheath is observed with age, which, together with the large myelinated fiber atrophy, might be the cause of the age-related decline in conduction velocity. A better understanding of the changes in aging peripheral nerves might improve interpretation of their pathological changes, as well as comprehension of their regeneration in individuals of different age.

Neuropeptide Y in the olfactory system, forebrain and pituitary of the teleost, Clarias batrachus.

PubMed

Gaikwad, Archana; Biju, K C; Saha, Subhash G; Subhedar, Nishikant

2004-03-01

Distribution of neuropeptide Y (NPY)-like immunoreactivity in the forebrain of catfish Clarias batrachus was examined with immunocytochemistry. Conspicuous immunoreactivity was seen in the olfactory receptor neurons (ORNs), their projections in the olfactory nerve, fascicles of the olfactory nerve layer in the periphery of bulb and in the medial olfactory tracts as they extend to the telencephalic lobes. Ablation of the olfactory organ resulted in loss of immunoreactivity in the olfactory nerve layer of the bulb and also in the fascicles of the medial olfactory tracts. This evidence suggests that NPY may serve as a neurotransmitter in the ORNs and convey chemosensory information to the olfactory bulb, and also to the telencephalon over the extrabulbar projections. In addition, network of beaded immunoreactive fibers was noticed throughout the olfactory bulb, which did not respond to ablation experiment. These fibers may represent centrifugal innervation of the bulb. Strong immunoreactivity was encountered in some ganglion cells of nervus terminalis. Immunoreactive fibers and terminal fields were widely distributed in the telencephalon. Several neurons of nucleus entopeduncularis were moderately immunoreactive; and a small population of neurons in nucleus preopticus periventricularis was also labeled. Immunoreactive terminal fields were particularly conspicuous in the preoptic, the tuberal areas, and the periventricular zone around the third ventricle and inferior lobes. NPY immunoreactive cells and fibers were detected in all the lobes of the pituitary gland. Present results describing the localization of NPY in the forebrain of C. batrachus are in concurrence with the pattern of the immunoreactivity encountered in other teleosts. However, NPY in olfactory system of C. batrachus is a novel feature that suggests a role for the peptide in processing of chemosensory information.

Optic nerve axons and acquired alterations in the appearance of the optic disc.

PubMed Central

Wirtschafter, J D

1983-01-01

The pathophysiologic events in optic nerve axons have recently been recognized as crucial to an understanding of clinically significant acquired alterations in the ophthalmoscopic appearance of the optic disc. Stasis and related abnormalities of axonal transport appear to explain most aspects of optic nerve head swelling, including optic disc drusen and retinal cottonwool spots. Loss of axoplasm and axonal death can be invoked to interpret optic disc pallor, thinning and narrowing of rim tissue, changes in the size and outline of the optic cup, laminar dots, atrophy of the retinal nerve fiber layer, and acquired demyelination and myelination of the retinal nerve fiber layer. It is speculated that the axons may also play a role in the mechanical support of the lamina cribrosa in resisting the pressure gradient across the pars scleralis of the optic nerve head. Axons and their associated glial cells may be involved in those cases where "reversibility" of cupping of the optic disc has been reported. The structure, physiology, and experimental pathologic findings of the optic nerve head have been reviewed. Many aspects concerning the final anatomic appearance of the optic nerve head have been explained. However, many questions remain concerning the intermediate mechanisms by which increased intracranial pressure retards the various components of axonal transport in papilledema and by which increased IOP causes axonal loss in glaucoma. Investigation of the molecular biology of axonal constituents and their responses to abnormalities in their physical and chemical milieu could extend our understanding of the events that result from mechanical compression and local ischemia. Moreover, we have identified a need to further explore the role of axons in the pathophysiology of optic disc cupping. Images FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 8 FIGURE 11 FIGURE 12 FIGURE 13 PMID:6203209

Nerve Fiber Activation During Peripheral Nerve Field Stimulation: Importance of Electrode Orientation and Estimation of Area of Paresthesia.

PubMed

Frahm, Ken Steffen; Hennings, Kristian; Vera-Portocarrero, Louis; Wacnik, Paul W; Mørch, Carsten Dahl

2016-04-01

Low back pain is one of the indications for using peripheral nerve field stimulation (PNFS). However, the effect of PNFS varies between patients; several stimulation parameters have not been investigated in depth, such as orientation of the nerve fiber in relation to the electrode. While placing the electrode parallel to the nerve fiber may give lower activation thresholds, anodal blocking may occur when the propagating action potential passes an anode. A finite element model was used to simulate the extracellular potential during PNFS. This was combined with an active cable model of Aβ and Aδ nerve fibers. It was investigated how the angle between the nerve fiber and electrode affected the nerve activation and whether anodal blocking could occur. Finally, the area of paresthesia was estimated and compared with any concomitant Aδ fiber activation. The lowest threshold was found when nerve and electrode were in parallel, and that anodal blocking did not appear to occur during PNFS. The activation of Aβ fibers was within therapeutic range (<10V) of PNFS; however, within this range, Aδ fiber activation also may occur. The combined area of activated Aβ fibers (paresthesia) was at least two times larger than Aδ fibers for similar stimulation intensities. No evidence of anodal blocking was observed in this PNFS model. The thresholds were lowest when the nerves and electrodes were parallel; thus, it may be relevant to investigate the overall position of the target nerve fibers prior to electrode placement. © 2015 International Neuromodulation Society.

Structured polarized light microscopy (SPLM) for mapping collagen fiber orientation of ocular tissues

NASA Astrophysics Data System (ADS)

Yang, Bin; Brazile, Bryn; Jan, Ning-Jiun; Voorhees, Andrew P.; Sigal, Ian A.

2018-02-01

Glaucoma is a disease characterized by progressive and irreversible vision loss leading to blindness. This vision loss is believed to be largely determined by the biomechanics of the optic nerve head region. Optic nerve head biomechanics, in turn, is determined by the properties of the constituent collagen. However, it is challenging to visualize and quantify collagen morphology and orientation in situ, and therefore often studies of the region collagen have used histological sections. Here we describe SPLM, a novel imaging technique that combines structured light illumination and polarized light microscopy (PLM) to enable collagen fiber visualization and fiber orientation mapping without requiring tissue sectioning. We developed a custom automated SPLM imaging system based on an upright microscope and a digital micromirror device (DMD) projector. The high spatial frequency patterns were used to achieve effective background suppression. Enhanced scattering sensitivity with SPLM resulted in images with highly improved visibility of collagen structures, even of tissues covered by pigment. SPLM produced improved fiber orientation maps from superficial layers compared to depth-averaged orientation from regular PLM. SPLM imaging provides valuable information of collagen fiber morphology and orientation in situ thus strengthening the study of ocular collagen fiber biomechanics and glaucoma.

Nerve Fiber Layer Thickness and Characteristics Associated with Glaucoma in Community Living Older Adults: Prelude to a Screening Trial?

PubMed

Klein, Barbara E K; Johnson, Chris A; Meuer, Stacy M; Lee, Kyungmoo; Wahle, Andreas; Lee, Kristine E; Kulkarni, Amruta; Sonka, Milan; Abràmoff, Michael D; Klein, Ronald

2017-04-01

To examine the associations of nerve fiber layer (NFL) thickness with other ocular characteristics in older adults. Participants in the Beaver Dam Eye Study (2008-2010) underwent spectral domain optical coherence tomography (SD-OCT) scans of the optic nerve head, imaging of optic discs, frequency doubling technology (FDT) perimetry, measurement of intraocular pressure (IOP), and an interview concerning their history of glaucoma and use of drops to lower eye pressure. Self-reported histories of glaucoma and the use of drops to lower eye pressure were obtained at follow-up examinations (2014-2016). NFL thickness measured on OCTs varied by location around the optic nerve. Age was associated with mean NFL thickness. Mean NFL was thinnest in eyes with larger cup/disc (C/D) ratios. Horizontal hemifield defects or other optic nerve-field defects were associated with thinner NFL. NFL in persons who reported taking eye drops for high intraocular pressure was thinner compared to those not taking drops. After accounting for the presence of high intraocular pressure, large C/D ratios or hemifield defects, eyes with thinner NFL in the arcades were more likely (OR = 2.3 for 30 micron thinner NFL, p = 0.04) to have incident glaucoma at examination 5 years later. Retinal NFL thickness was associated with a new history of self-reported glaucoma 5 years later. A trial testing the usefulness of NFL as part of a screening battery for predicting glaucoma in those previously undiagnosed might lead to improved case finding and, ultimately, to diminishing the risk of visual field loss.

Changes in rabbit corneal innervation induced by the topical application of benzalkonium chloride.

PubMed

Chen, Wensheng; Zhang, Zhenhao; Hu, Jiaoyue; Xie, Hui; Pan, Juxin; Dong, Nuo; Liu, Zuguo

2013-12-01

To investigate the effect of benzalkonium chloride (BAK) on corneal nerves. Fifty-four adult New Zealand Albino rabbits were randomly divided into 3 groups. BAK at concentrations of 0.005%, 0.01%, or 0.02% was applied once daily to 1 eye of each rabbit for 9 days. The contralateral untreated eyes were used as controls. Corneal mechanical sensitivity, aqueous tear production, tear break-up time (BUT), fluorescein, and Rose Bengal staining scores were compared with those of control values on days 3, 6, and 9. Corneal whole mounts were immunostained with a specific antitubulin βIII antibody to label nerve fibers. Epithelial superficial nerve terminal, subbasal, and stromal nerve fiber densities were quantified. The structure of the central cornea was examined by means of in vivo confocal microscopy on day 9. The topical application of BAK resulted in lower corneal sensitivity and higher Rose Bengal staining scores on day 3, whereas there were no significant changes in the BUT, Schirmer, and corneal fluorescein scores. Decreased nerve densities in superficial and subbasal layers were observed in BAK-treated eyes on days 3 and 6, respectively. The eyes treated with 0.02% BAK exhibited significantly reduced Schirmer scores, BUT, and stromal nerve fiber density, and increased fluorescein staining scores on day 9. Corneal superficial epithelial cell size was significantly larger in all BAK-treated eyes compared with that in control eyes. The topical application of BAK can quickly cause corneal hypoesthesia without tear deficiency. Changes in corneal innervation significantly correlate with BAK-induced ocular surface changes.

Cell-type specific short-term plasticity at auditory nerve synapses controls feed-forward inhibition in the dorsal cochlear nucleus.

PubMed

Sedlacek, Miloslav; Brenowitz, Stephan D

2014-01-01

Feed-forward inhibition (FFI) represents a powerful mechanism by which control of the timing and fidelity of action potentials in local synaptic circuits of various brain regions is achieved. In the cochlear nucleus, the auditory nerve provides excitation to both principal neurons and inhibitory interneurons. Here, we investigated the synaptic circuit associated with fusiform cells (FCs), principal neurons of the dorsal cochlear nucleus (DCN) that receive excitation from auditory nerve fibers and inhibition from tuberculoventral cells (TVCs) on their basal dendrites in the deep layer of DCN. Despite the importance of these inputs in regulating fusiform cell firing behavior, the mechanisms determining the balance of excitation and FFI in this circuit are not well understood. Therefore, we examined the timing and plasticity of auditory nerve driven FFI onto FCs. We find that in some FCs, excitatory and inhibitory components of FFI had the same stimulation thresholds indicating they could be triggered by activation of the same fibers. In other FCs, excitation and inhibition exhibit different stimulus thresholds, suggesting FCs and TVCs might be activated by different sets of fibers. In addition, we find that during repetitive activation, synapses formed by the auditory nerve onto TVCs and FCs exhibit distinct modes of short-term plasticity. Feed-forward inhibitory post-synaptic currents (IPSCs) in FCs exhibit short-term depression because of prominent synaptic depression at the auditory nerve-TVC synapse. Depression of this feedforward inhibitory input causes a shift in the balance of fusiform cell synaptic input towards greater excitation and suggests that fusiform cell spike output will be enhanced by physiological patterns of auditory nerve activity.

Changes in Inner and Outer Retinal Layer Thicknesses after Vitrectomy for Idiopathic Macular Hole: Implications for Visual Prognosis

PubMed Central

Hashimoto, Yuki; Saito, Wataru; Fujiya, Akio; Yoshizawa, Chikako; Hirooka, Kiriko; Mori, Shohei; Noda, Kousuke; Ishida, Susumu

2015-01-01

Purpose To investigate sequential post-operative thickness changes in inner and outer retinal layers in eyes with an idiopathic macular hole (MH). Methods Retrospective case series. Twenty-four eyes of 23 patients who had received pars plana vitrectomy (PPV) for the closure of MH were included in the study. Spectral domain optical coherence tomography C-scan was used to automatically measure the mean thickness of the inner and outer retinal layers pre-operatively and up to 6 months following surgery. The photoreceptor outer segment (PROS) length was measured manually and was used to assess its relationship with best-corrected visual acuity (BCVA). Results Compared with the pre-operative thickness, the inner layers significantly thinned during follow-up (P = 0.02), particularly in the parafoveal (P = 0.01), but not perifoveal, area. The post-operative inner layer thinning ranged from the ganglion cell layer to the inner plexiform layer (P = 0.002), whereas the nerve fiber layer was unaltered. Outer layer thickness was significantly greater post-operatively (P = 0.002), and especially the PROS lengthened not only in the fovea but also in the parafovea (P < 0.001). Six months after surgery, BCVA was significantly correlated exclusively with the elongated foveal PROS (R = 0.42, P = 0.03), but not with any of the other thickness parameters examined. Conclusions Following PPV for MH, retinal inner layers other than the nerve fiber layer thinned, suggestive of subclinical thickening in the inner layers where no cyst was evident pre-operatively. In contrast, retinal outer layer thickness significantly increased, potentially as a result of PROS elongation linking tightly with favorable visual prognosis in MH eyes. PMID:26291526

Ultrastructural and cytochemical evidence for single impulse initiation zones in vestibular macular nerve fibers of rat

NASA Technical Reports Server (NTRS)

Ross, Muriel D.; Chee, Oliver; Black, Samuel; Cutler, Lynn

1991-01-01

Cupric ion-ferricyanide labeling methods and related ferrocyanide-stained tissues were used to locate the characterize, at the ultrastructural level, presumptive impulse initiation zones in the three types of vestibular macular nerve fibers. Large-diameter, M-type vestibular nerve fibers terminate in a calyx at the heminode, and labeling is coextensive with the base of the calyx. Intermediate, M/U-type nerve fibers have short, unmyelinated preterminal segments that sometimes bifurcate intamacularly, and small-diameter, U-type nerve fibers have long, unmyelinated preterminal axons and up to three branches. Preterminals of these nerve fibers display ultrastructural heterogeneity that is correlated with labeling patterns for sodium channels and/or associated polyanionic sites. They have a nodelike ultrastructure and label heavily from near the heminode to the base of the macula. Their intramacular branches, less organized ultrastructurally, label only slightly. Results indicate that vestibular nerve fibers have one impulse initiation zone, located near the heminode, that varies in length according to nerve fiber type. Structural heterogeneity may favor impulse conduction in the central direction, and length of the impulse initiation zone could influence nerve discharge patterns.

Conversion of muscle fiber types in regenerating chicken muscles following cross-reinnervation.

PubMed

Kikuchi, T; Akiba, T; Ashmore, C R

1986-01-01

Slow-tonic anterior latissimus dorsi (ALD) and fast-twitch posterior latissimus dorsi (PLD) muscles of 7 to 10-day-old White Leghorn chickens were crushed and allowed to be reinnervated by their own nerve, or crushed and transplanted to the other side and allowed to be reinnervated by the nerve of the side to which they were transplanted. Following transplantation, changes in the weight of the muscle, fiber-type composition and innervation pattern during regeneration were investigated. Normal growth rate of PLD was about twice that of ALD. Regenerating PLD, however, atrophied rapidly after crushing and denervation whether innervated by its own nerve or the other nerve type, whereas ALD reinnervated by its own nerve showed marked hypertrophy. PLD fibers transformed rapidly to fast-twitch alpha or slow-tonic (ST) fibers when they were reinnervated by PLD or ALD nerve, respectively. When ALD fibers were reinnervated by their own nerve, they differentiated into ST fibers that were surrounded by smaller immature fibers. ALD fibers were, however, resistant to complete control by fast-twitch PLD nerve and contained a large number of slow fibers (ST and beta) long after transplantation. Slow fibers in regenerates were initially multiply innervated, but later transformed into fast-twitch alpha fibers that were focally innervated. The mode of differentiation and innervation pattern of different muscle fiber types in regenerating muscles are discussed.

Hierarchical models for epidermal nerve fiber data.

PubMed

Andersson, Claes; Rajala, Tuomas; Särkkä, Aila

2018-02-10

While epidermal nerve fiber (ENF) data have been used to study the effects of small fiber neuropathies through the density and the spatial patterns of the ENFs, little research has been focused on the effects on the individual nerve fibers. Studying the individual nerve fibers might give a better understanding of the effects of the neuropathy on the growth process of the individual ENFs. In this study, data from 32 healthy volunteers and 20 diabetic subjects, obtained from suction induced skin blister biopsies, are analyzed by comparing statistics for the nerve fibers as a whole and for the segments that a nerve fiber is composed of. Moreover, it is evaluated whether this type of data can be used to detect diabetic neuropathy, by using hierarchical models to perform unsupervised classification of the subjects. It is found that using the information about the individual nerve fibers in combination with the ENF counts yields a considerable improvement as compared to using the ENF counts only. Copyright © 2017 John Wiley & Sons, Ltd.

Change of Retinal Nerve Layer Thickness in Non-Arteritic Anterior Ischemic Optic Neuropathy Revealed by Fourier Domain Optical Coherence Tomography.

PubMed

Han, Mei; Zhao, Chen; Han, Quan-Hong; Xie, Shiyong; Li, Yan

2016-08-01

To examine the changes of non-arteritic anterior ischemic optic neuropathy (NAION) by serial morphometry using Fourier domain optical coherence tomography (FD-OCT). Retrospective study in patients with newly diagnosed NAION (n=33, all unilateral) and controls (n=75 unilateral NAION patients with full contralateral eye vision) who underwent FD-OCT of the optic disk, optic nerve head (ONH), and macula within 1 week of onset and again 1, 3, 6, and 12 months later. The patients showed no improvement in vision during follow-up. Within 1 week of onset, all NAION eyes exhibited severe ONH fiber crowding and peripapillary retinal nerve fiber layer (RNFL) edema. Four had subretinal fluid accumulation and 12 had posterior vitreous detachment (PVD) at the optic disc surface. Ganglion cell complex (GCC) and RNFL thicknesses were reduced at 1 and 3 months (p < 0.05), with no deterioration thereafter. Initial RNFL/GCC contraction magnitude in the superior hemisphere correlated with the severity of inferior visual field deficits. NAION progression is characterized by an initial phase of accelerated RNFL and GCC deterioration. These results reveal that the kinetic change of neural retina in NAION and may have implication on the time window for treatment of NAION. FD-OCT is useful in the evaluation of NAION.

The dimensions and characteristics of the subepidermal nerve plexus in human skin--terminal Schwann cells constitute a substantial cell population within the superficial dermis.

PubMed

Reinisch, Christina M; Tschachler, Erwin

2012-03-01

The skin constitutes the largest sensorial organ. Its nervous system consists of different types of afferent nerve fibers which spread out immediately beneath the skin surface to sense temperature, touch and pain. Our aim was to investigate the dimension and topographic relationship of the different nerve fibers of the subepidermal nerve plexus in human hairy skin and to analyze numbers and marker expression of terminal Schwann cells. Nerve fibers and Schwann cells were investigated on dermal sheet preparations and thick sections of skin from various body regions of 10 individuals. The dimension of subepidermal nerve fibers varied between different body sites with highest values in chest skin (100 ± 18 mm/mm(2)) and lowest in posterior forearm skin (53 ± 10 mm/mm(2)). The majority of fibers (85.79%) were unmyelinated, thus representing C-fibers, of which 7.84% were peptidergic. Neurofilament-positive fibers (A-fibers) accounted for 14.21% and fibers positive for both neurofilament and myelin (Aβ-fibers) for only 0.18%. The number of Schwann cells varied in accordance with nerve fiber length from 453 ± 108 on chest skin to 184 ± 58/mm(2) in skin of the posterior forearm. Terminal Schwann cells showed a marker profile comparable to Schwann cells in peripheral nerves with the notable exception of expression of NGFr, NCAM, L1CAM and CD146 on myelinating Schwann cells in the dermis but not in peripheral nerves. Our data show that terminal Schwann cells constitute a substantial cell population within the papillary dermis and that both nerve fiber length and Schwann cell numbers vary considerably between different body sites. Copyright © 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Evaluation of retinal nerve fiber layer thickness profile in thyroid ophthalmopathy without optic nerve dysfunction

PubMed Central

Mugdha, Kumari; Kaur, Apjit; Sinha, Neha; Saxena, Sandeep

2016-01-01

AIM To evaluate retinal nerve fiber layer (RNFL) thickness profile in patients of thyroid ophthalmopathy with no clinical signs of optic nerve dysfunction. METHODS A prospective, case-control, observational study conducted at a tertiary care centre. Inclusion criteria consisted of patients with eyelid retraction in association with any one of: biochemical thyroid dysfunction, exophthalmos, or extraocular muscle involvement; or thyroid dysfunction in association with either exophthalmos or extra-ocular muscle involvement; or a clinical activity score (CAS)>3/7. Two measurements of RNFL thickness were done for each eye, by Cirrus HD-optical coherence tomography 6mo apart. RESULTS Mean age of the sample was 38.75y (range 13-70y) with 18 males and 22 females. Average RNFL thickness at first visit was 92.06±12.44 µm, significantly lower than control group (101.28±6.64 µm) (P=0.0001). Thickness of inferior quadrant decreased from 118.2±21.27 µm to 115.0±22.27 µm after 6mo (P=0.02). There was no correlation between the change in CAS and RNFL thickness. CONCLUSION Decreased RNFL thickness is an important feature of thyroid orbitopathy, which is an inherent outcome of compressive optic neuropathy of any etiology. Subclinical RNFL damage continues in the absence of clinical activity of the disease. RNFL evaluation is essential in Grave's disease and active intervention may be warranted in the presence of significant damage. PMID:27990368

Influence of corneal power on circumpapillary retinal nerve fiber layer and optic nerve head measurements by spectral-domain optical coherence tomography.

PubMed

Hirasawa, Kazunori; Shoji, Nobuyuki

2017-01-01

To evaluate the influence of corneal power on circumpapillary retinal nerve fiber layer (cpRNFL) and optic nerve head (ONH) measurements by spectral-domain optical coherence tomography (SD-OCT). Twenty-five eyes of 25 healthy participants (mean age 23.6±3.6y) were imaged by SD-OCT using horizontal raster scans. Disposable soft contact lenses of different powers (from -11 to +5 diopters including 0 diopter) were worn to induce 2-diopter changes in corneal power. Differences in the cpRNFL and ONH measurements per diopter of change in corneal power were analyzed. As corneal power increased by 1 diopter, total and quadrant cpRNFL thicknesses, except for the nasal sector, decreased by --0.19 to -0.32 µm ( P <0.01). Furthermore, the disc, cup, and rim areas decreased by -0.017, -0.007, and -0.015 mm 2 , respectively ( P <0.001); the cup and rim volumes decreased by -0.0013 and -0.006 mm 3 , respectively ( P <0.01); and the vertical and horizontal disc diameters decreased by -0.006 and -0.007 mm, respectively ( P <0.001). For more precise OCT imaging, the ocular magnification should be corrected by considering both the axial length and corneal power. However, the effect of corneal power changes on cpRNFL thickness and ONH topography are small when compare with those of the axial length.

Changes in Macular Retinal Layers and Peripapillary Nerve Fiber Layer Thickness after 577-nm Pattern Scanning Laser in Patients with Diabetic Retinopathy

PubMed Central

Shin, Ji Soo

2017-01-01

Purpose The aim of this study was to evaluate the changes in thickness of each macular retinal layer, the peripapillary retinal nerve fiber layer (RNFL), and central macular thickness (CMT) after 577-nm pattern scanning laser (PASCAL) photocoagulation in patients with diabetic retinopathy. Methods This retrospective study included 33 eyes with diabetic retinopathy that underwent 577-nm PASCAL photocoagulation. Each retinal layer thickness, peripapillary RNFL thickness, and CMT were measured by spectral-domain optical coherence tomography before 577-nm PASCAL photocoagulation, as well as at 1, 6, and 12 months after 577-nm PASCAL photocoagulation. Computerized intraretinal segmentation of optical coherence tomography was performed to identify the thickness of each retinal layer. Results The average thickness of the RNFL, ganglion cell layer, inner plexiform layer, inner nuclear layer, inner retinal layer, and CMT at each follow-up increased significantly from baseline (p < 0.001), whereas that of the retinal pigment epithelium at each follow-up decreased significantly from baseline (p < 0.001). The average thickness of the peripapillary RNFL increased significantly at one month (p < 0.001). This thickness subsequently recovered to 7.48 µm, and there were no significant changes at six or 12 months compared to baseline (p > 0.05). Conclusions Each macular retinal layer and CMT had a tendency to increase for one year after 577-nm PASCAL photocoagulation, whereas the average thickness of retinal pigment epithelium decreased at one-year follow-up compared to the baseline. Although an increase in peripapillary RNFL thickness was observed one month after 577-nm PASCAL photocoagulation, there were no significant changes at the one-year follow-up compared to the baseline. PMID:29022292

Changes in Macular Retinal Layers and Peripapillary Nerve Fiber Layer Thickness after 577-nm Pattern Scanning Laser in Patients with Diabetic Retinopathy.

PubMed

Shin, Ji Soo; Lee, Young Hoon

2017-12-01

The aim of this study was to evaluate the changes in thickness of each macular retinal layer, the peripapillary retinal nerve fiber layer (RNFL), and central macular thickness (CMT) after 577-nm pattern scanning laser (PASCAL) photocoagulation in patients with diabetic retinopathy. This retrospective study included 33 eyes with diabetic retinopathy that underwent 577-nm PASCAL photocoagulation. Each retinal layer thickness, peripapillary RNFL thickness, and CMT were measured by spectral-domain optical coherence tomography before 577-nm PASCAL photocoagulation, as well as at 1, 6, and 12 months after 577-nm PASCAL photocoagulation. Computerized intraretinal segmentation of optical coherence tomography was performed to identify the thickness of each retinal layer. The average thickness of the RNFL, ganglion cell layer, inner plexiform layer, inner nuclear layer, inner retinal layer, and CMT at each follow-up increased significantly from baseline (p < 0.001), whereas that of the retinal pigment epithelium at each follow-up decreased significantly from baseline (p < 0.001). The average thickness of the peripapillary RNFL increased significantly at one month (p < 0.001). This thickness subsequently recovered to 7.48 μm, and there were no significant changes at six or 12 months compared to baseline (p > 0.05). Each macular retinal layer and CMT had a tendency to increase for one year after 577-nm PASCAL photocoagulation, whereas the average thickness of retinal pigment epithelium decreased at one-year follow-up compared to the baseline. Although an increase in peripapillary RNFL thickness was observed one month after 577-nm PASCAL photocoagulation, there were no significant changes at the one-year follow-up compared to the baseline. © 2017 The Korean Ophthalmological Society

High-resolution measurement of electrically-evoked vagus nerve activity in the anesthetized dog

NASA Astrophysics Data System (ADS)

Yoo, Paul B.; Lubock, Nathan B.; Hincapie, Juan G.; Ruble, Stephen B.; Hamann, Jason J.; Grill, Warren M.

2013-04-01

Objective. Not fully understanding the type of axons activated during vagus nerve stimulation (VNS) is one of several factors that limit the clinical efficacy of VNS therapies. The main goal of this study was to characterize the electrical recruitment of both myelinated and unmyelinated fibers within the cervical vagus nerve. Approach. In anesthetized dogs, recording nerve cuff electrodes were implanted on the vagus nerve following surgical excision of the epineurium. Both the vagal electroneurogram (ENG) and laryngeal muscle activity were recorded in response to stimulation of the right vagus nerve. Main results. Desheathing the nerve significantly increased the signal-to-noise ratio of the ENG by 1.2 to 9.9 dB, depending on the nerve fiber type. Repeated VNS following nerve transection or neuromuscular block (1) enabled the characterization of A-fibers, two sub-types of B-fibers, and unmyelinated C-fibers, (2) confirmed the absence of stimulation-evoked reflex compound nerve action potentials in both the ipsilateral and contralateral vagus nerves, and (3) provided evidence of stimulus spillover into muscle tissue surrounding the stimulating electrode. Significance. Given the anatomical similarities between the canine and human vagus nerves, the results of this study provide a template for better understanding the nerve fiber recruitment patterns associated with VNS therapies.

Scanning laser topography and scanning laser polarimetry: comparing both imaging methods at same distances from the optic nerve head.

PubMed

Kremmer, Stephan; Keienburg, Marcus; Anastassiou, Gerasimos; Schallenberg, Maurice; Steuhl, Klaus-Peter; Selbach, J Michael

2012-01-01

To compare the performance of scanning laser topography (SLT) and scanning laser polarimetry (SLP) on the rim of the optic nerve head and its surrounding area and thereby to evaluate whether these imaging technologies are influenced by other factors beyond the thickness of the retinal nerve fiber layer (RNFL). A total of 154 eyes from 5 different groups were examined: young healthy subjects (YNorm), old healthy subjects (ONorm), patients with normal tension glaucoma (NTG), patients with open-angle glaucoma and early glaucomatous damage (OAGE) and patients with open-angle glaucoma and advanced glaucomatous damage (OAGA). SLT and SLP measurements were taken. Four concentric circles were superimposed on each of the images: the first one measuring at the rim of the optic nerve head (1.0 ONHD), the next measuring at 1.25 optic nerve head diameters (ONHD), at 1.5 ONHD and at 1.75 ONHD. The aligned images were analyzed using GDx/NFA software. Both methods showed peaks of RNFL thickness in the superior and inferior segments of the ONH. The maximum thickness, registered by the SLT device was at the ONH rim where the SLP device tended to measure the lowest values. SLT measurements at the ONH were influenced by other tissues besides the RNFL like blood vessels and glial tissues. SLT and SLP were most strongly correlated at distances of 1.25 and 1.5 ONHD. While both imaging technologies are valuable tools in detecting glaucoma, measurements at the ONH rim should be interpreted critically since both methods might provide misleading results. For the assessment of the retinal nerve fiber layer we would like to recommend for both imaging technologies, SLT and SLP, measurements in 1.25 and 1.5 ONHD distance of the rim of the optic nerve head.

Response of feline intradental nerve fibers to tooth cutting by Er:YAG laser.

PubMed

Chaiyavej, S; Yamamoto, H; Takeda, A; Suda, H

2000-01-01

The aim of this study was to investigate the response of intradental A- and C-fibers during tooth cutting by Er:YAG laser. Bipolar electrical stimulation was applied to the cat's canine to identify functional single nerve fibers of the inferior alveolar nerve. The tip of the canine tooth was cut in 0.5-mm steps until the pulp was exposed. Teeth were alternately cut by using Er:YAG laser (50 mJ, 5 pps) and micromotor under water cooling. The nerve response recorded from the single nerve fibers during laser cutting was compared with that during micromotor cutting. All 26 A-fibers responded to laser cutting with high frequency of nerve firings. The nerve firing rate was significantly higher during laser cutting compared with that during micromotor cutting of superficial dentin (Chi(2) test, P < 0.05) but was not significantly different at deep dentin (P > or = 0. 05). Nine of 11 C-fibers responded to laser cutting when the deep dentin was cut. Among those nine nerve fibers, three also showed a low frequency response to laser cutting of the superficial dentin. During the tooth cutting, Er:YAG laser was more effective in activating intradental A-fibers compared with micromotor and also caused the activation of intradental C-fibers. Copyright 2000 Wiley-Liss, Inc.

Retinal nerve fiber layer measurements by scanning laser polarimetry with enhanced corneal compensation in healthy subjects.

PubMed

Rao, Harsha L; Venkatesh, Chirravuri R; Vidyasagar, Kelli; Yadav, Ravi K; Addepalli, Uday K; Jude, Aarthi; Senthil, Sirisha; Garudadri, Chandra S

2014-12-01

To evaluate the (i) effects of biological (age and axial length) and instrument-related [typical scan score (TSS) and corneal birefringence] parameters on the retinal nerve fiber layer (RNFL) measurements and (ii) repeatability of RNFL measurements with the enhanced corneal compensation (ECC) protocol of scanning laser polarimetry (SLP) in healthy subjects. In a cross-sectional study, 140 eyes of 73 healthy subjects underwent RNFL imaging with the ECC protocol of SLP. Linear mixed modeling methods were used to evaluate the effects of age, axial length, TSS, and corneal birefringence on RNFL measurements. One randomly selected eye of 48 subjects from the cohort underwent 3 serial scans during the same session to determine the repeatability. Age significantly influenced all RNFL measurements. RNFL measurements decreased by 1 µm for every decade increase in age. TSS affected the overall average RNFL measurement (β=-0.62, P=0.003), whereas residual anterior segment retardance affected the superior quadrant measurement (β=1.14, P=0.01). Axial length and corneal birefringence measurements did not influence RNFL measurements. Repeatability, as assessed by the coefficient of variation, ranged between 1.7% for the overall average RNFL measurement and 11.4% for th nerve fiber indicator. Age significantly affected all RNFL measurements with the ECC protocol of SLP, whereas TSS and residual anterior segment retardance affected the overall average and the superior average RNFL measurements, respectively. Axial length and corneal birefringence measurements did not influence any RNFL measurements. RNFL measurements had good intrasession repeatability. These results are important while evaluating the change in structural measurements over time in glaucoma patients.

Effect of cataract surgery on retinal nerve fiber layer thickness parameters using scanning laser polarimetry (GDxVCC).

PubMed

Dada, Tanuj; Behera, Geeta; Agarwal, Anand; Kumar, Sanjeev; Sihota, Ramanjit; Panda, Anita

2010-01-01

To study the effect of cataract extraction on the retinal nerve fiber layer (RNFL) thickness, and assessment by scanning laser polarimetry (SLP), with variable corneal compensation (GDx VCC), at the glaucoma service of a tertiary care center in North India. Thirty-two eyes of 32 subjects were enrolled in the study. The subjects underwent RNFL analysis by SLP (GDx VCC) before undergoing phacoemulsification cataract extraction with intraocular lens (IOL) implantation (Acrysof SA 60 AT) four weeks following cataract surgery. The RNFL thickness parameters evaluated both before and after surgery included temporal, superior, nasal, inferior, temporal (TSNIT) average, superior average, inferior average, and nerve fiber index (NFI). The mean age of subjects was 57.6 +/- 11.7 years (18 males, 14 females). Mean TSNIT average thickness (microm) pre- and post-cataract surgery was 49.2 +/- 14.1 and 56.5 +/- 7.6 ( P = 0.001). There was a statistically significant increase in RNFL thickness parameters (TSNIT average, superior average, and inferior average) and decrease in NFI post-cataract surgery as compared to the baseline values. Mean NFI pre- and post-cataract surgery was 41.3 +/- 15.3 and 21.6 +/- 11.8 ( P = 0.001). Measurement of RNFL thickness parameters by scanning laser polarimetry is significantly altered following cataract surgery. Post the cataract surgery, a new baseline needs to be established for assessing the longitudinal follow-up of a glaucoma patient. The presence of cataract may lead to an underestimation of the RNFL thickness, and this should be taken into account when analyzing progression in a glaucoma patient.

Reflectance Speckle of Retinal Nerve Fiber Layer Reveals Axonal Activity

PubMed Central

Huang, Xiang-Run; Knighton, Robert W.; Zhou, Ye; Zhao, Xiao-Peng

2013-01-01

Purpose. This study investigated the retinal nerve fiber layer (RNFL) reflectance speckle and tested the hypothesis that temporal change of RNFL speckle reveals axonal dynamic activity. Methods. RNFL reflectance speckle of isolated rat retinas was studied with monochromatic illumination. A series of reflectance images was collected every 5 seconds for approximately 15 minutes. Correlation coefficients (CC) of selected areas between a reference and subsequent images were calculated and plotted as a function of the time intervals between images. An exponential function fit to the time course was used to evaluate temporal change of speckle pattern. To relate temporal change of speckle to axonal activity, in vitro living retina perfused at a normal (34°C) and a lower (24°C) temperature, paraformaldehyde-fixed retina, and retina treated with microtubule depolymerization were used. Results. RNFL reflectance was not uniform; rather nerve fiber bundles had a speckled texture that changed with time. In normally perfused retina, the time constant of the CC change was 0.56 ± 0.26 minutes. In retinas treated with lower temperature and microtubule depolymerization, the time constants increased by two to four times, indicating that the speckle pattern changed more slowly. The speckled texture in fixed retina was stationary. Conclusions. Fixation stops axonal activity; treatments with either lower temperature or microtubule depolymerization are known to decrease axonal transport. The results obtained in this study suggest that temporal change of RNFL speckle reveals structural change due to axonal activity. Assessment of RNFL reflectance speckle may offer a new means of evaluating axonal function. PMID:23532525

Cupping in the Monkey Optic Nerve Transection Model Consists of Prelaminar Tissue Thinning in the Absence of Posterior Laminar Deformation

PubMed Central

Ing, Eliesa; Ivers, Kevin M.; Yang, Hongli; Gardiner, Stuart K.; Reynaud, Juan; Cull, Grant; Wang, Lin; Burgoyne, Claude F.

2016-01-01

Purpose To use optical coherence tomography (OCT) to test the hypothesis that optic nerve head (ONH) “cupping” in the monkey optic nerve transection (ONT) model does not include posterior laminar deformation. Methods Five monkeys (aged 5.5–7.8 years) underwent ONH and retinal nerve fiber layer (RNFL) OCT imaging five times at baseline and biweekly following unilateral ONT until euthanization at ∼40% RNFL loss. Retinal nerve fiber layer thickness (RNFLT) and minimum rim width (MRW) were calculated from each pre- and post-ONT imaging session. The anterior lamina cribrosa surface (ALCS) was delineated within baseline and pre-euthanasia data sets. Significant ONT versus control eye pre-euthanasia change in prelaminar tissue thickness (PLTT), MRW, RNFLT, and ALCS depth (ALCSD) was determined using a linear mixed-effects model. Eye-specific change in each parameter exceeded the 95% confidence interval constructed from baseline measurements. Results Animals were euthanized 49 to 51 days post ONT. Overall ONT eye change from baseline was significant for MRW (−26.2%, P = 0.0011), RNFLT (−43.8%, P < 0.0001), PLTT (−23.8%, P = 0.0013), and ALCSD (−20.8%, P = 0.033). All five ONT eyes demonstrated significant eye-specific decreases in MRW (−23.7% to −31.8%) and RNFLT (−39.6% to −49.7%). Four ONT eyes showed significant PLTT thinning (−23.0% to −28.2%). The ALCS was anteriorly displaced in three of the ONT eyes (−25.7% to −39.2%). No ONT eye demonstrated posterior laminar displacement. Conclusions Seven weeks following surgical ONT in the monkey eye, ONH cupping involves prelaminar and rim tissue thinning without posterior deformation of the lamina cribrosa. PMID:27168368

Differences in Optic Nerve Head, Retinal Nerve Fiber Layer, and Ganglion Cell Complex Parameters Between Caucasian and Chinese Subjects.

PubMed

Chansangpetch, Sunee; Huang, Guofu; Coh, Paul; Oldenburg, Catherine; Amoozgar, Behzad; He, Mingguang; Lin, Shan C

2018-04-01

To compare optic nerve head, peripapillary retinal nerve fiber layer (pRNFL), and ganglion cell complex (GCC) parameters between Caucasian and ethnic Chinese. Normal subjects above 40 years old and self-identified as being Caucasian and Chinese were recruited. They were evaluated with spectral-domain optical coherence tomography (RTVue-100). Parameters related to the optic nerve head, pRNFL, and GCC analysis protocols were acquired. Multivariable linear regression was performed adjusting for potential confounders. Data from 116 Caucasian and 130 Chinese subjects were available for analysis. Mean age of all participants was 66.72 (SD 10.82) years. There were statistically significant differences for disc area (DA), area cup-to-disc, vertical cup-to-disc, and cup volume (P=0.02, 0.004, 0.02, and 0.03, respectively), greater in Chinese. After adjusting for age, sex, axial length (AL), intraocular pressure (IOP), DA, and GCC thickness, Chinese subjects had significantly greater thickness in all pRNFL parameters (mean differences ranged between 4.29 and 9.93 μm; all P<0.001) except the nasal quadrant. GCC outcomes were also adjusted for DA and pRNFL; Caucasians had significantly higher average GCC and inferior GCC (mean difference 2.97 and 3.45 μm, respectively; P<0.01), whereas the Chinese group had significantly higher ganglion cell global loss volume (mean difference 2.47 %, P<0.001). This study suggests there is significantly greater pRNFL thickness in Chinese, which were independent of age, AL, IOP, and DA, and possibly greater GCC in Caucasians after adjustment for age, AL, IOP, DA, and pRNFL thickness.

Automated diagnosis of diabetic retinopathy and glaucoma using fundus and OCT images.

PubMed

Pachiyappan, Arulmozhivarman; Das, Undurti N; Murthy, Tatavarti Vsp; Tatavarti, Rao

2012-06-13

We describe a system for the automated diagnosis of diabetic retinopathy and glaucoma using fundus and optical coherence tomography (OCT) images. Automatic screening will help the doctors to quickly identify the condition of the patient in a more accurate way. The macular abnormalities caused due to diabetic retinopathy can be detected by applying morphological operations, filters and thresholds on the fundus images of the patient. Early detection of glaucoma is done by estimating the Retinal Nerve Fiber Layer (RNFL) thickness from the OCT images of the patient. The RNFL thickness estimation involves the use of active contours based deformable snake algorithm for segmentation of the anterior and posterior boundaries of the retinal nerve fiber layer. The algorithm was tested on a set of 89 fundus images of which 85 were found to have at least mild retinopathy and OCT images of 31 patients out of which 13 were found to be glaucomatous. The accuracy for optical disk detection is found to be 97.75%. The proposed system therefore is accurate, reliable and robust and can be realized.

Automated diagnosis of diabetic retinopathy and glaucoma using fundus and OCT images

PubMed Central

2012-01-01

We describe a system for the automated diagnosis of diabetic retinopathy and glaucoma using fundus and optical coherence tomography (OCT) images. Automatic screening will help the doctors to quickly identify the condition of the patient in a more accurate way. The macular abnormalities caused due to diabetic retinopathy can be detected by applying morphological operations, filters and thresholds on the fundus images of the patient. Early detection of glaucoma is done by estimating the Retinal Nerve Fiber Layer (RNFL) thickness from the OCT images of the patient. The RNFL thickness estimation involves the use of active contours based deformable snake algorithm for segmentation of the anterior and posterior boundaries of the retinal nerve fiber layer. The algorithm was tested on a set of 89 fundus images of which 85 were found to have at least mild retinopathy and OCT images of 31 patients out of which 13 were found to be glaucomatous. The accuracy for optical disk detection is found to be 97.75%. The proposed system therefore is accurate, reliable and robust and can be realized. PMID:22695250

Comparison of Ganglion Cell and Retinal Nerve Fiber Layer Thickness in Pigment Dispersion Syndrome, Pigmentary Glaucoma, and Healthy Subjects with Spectral-domain OCT.

PubMed

Arifoglu, Hasan Basri; Simavli, Huseyin; Midillioglu, Inci; Berk Ergun, Sule; Simsek, Saban

2017-01-01

To evaluate the ganglion cell complex (GCC) and retinal nerve fiber layer (RNFL) thickness in pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG) with RTVue spectral domain optical coherence tomography (SD-OCT). A total of 102 subjects were enrolled: 29 with PDS, 18 with PG, and 55 normal subjects. Full ophthalmic examination including visual field analysis was performed. SD-OCT was used to analyze GCC superior, GCC inferior, and average RNFL thickness. To compare the discrimination capabilities, the areas under the receiver operating characteristic curves were assessed. Superior GCC, inferior GCC, and RNFL thickness values of patients with PG were statistically signicantly lower than those of patients with PDS (p < 0.001) and healthy individuals (p < 0.001 for all). No statistically significant difference was found between PDS and normal subjects in same parameters (p > 0.05). The SD-OCT-derived GCC and RNFL thickness parameters can be useful to discriminate PG from both PDS and normal subjects.

Comparison between the Correlations of Retinal Nerve Fiber Layer Thickness Measured by Spectral Domain Optical Coherence Tomography and Visual Field Defects in Standard Automated White-on-White Perimetry versus Pulsar Perimetry

PubMed Central

Hömberg, Lisann; Eter, Nicole

2017-01-01

Purpose To compare the structure-function relationships between retinal nerve fiber layer thickness (RNFLT) and visual field defects measured either by standard automated perimetry (SAP) or by Pulsar perimetry (PP). Materials and Methods 263 eyes of 143 patients were prospectively included. Depending on the RNFLT, patients were assigned to the glaucoma group (group A: RNFL score 3–6) or the control group (group B: RNFL score 0–2). Structure-function relationships between RNFLT and mean sensitivity (MS) measured by SAP and PP were analyzed. Results Throughout the entire group, the MS assessed by PP and SAP correlated significantly with RNFLT in all sectors. In the glaucoma group, there was no significant difference between the correlations RNFL-SAP and RNFL-PP, whereas a significant difference was found in the control group. Conclusions In the control group, the correlation between structure and function based on the PP data was significantly stronger than that based on SAP. PMID:29119021

Anatomic distribution of nerves and microvascular density in the human anterior vaginal wall: prospective study.

PubMed

Li, Ting; Liao, Qinping; Zhang, Hong; Gao, Xuelian; Li, Xueying; Zhang, Miao

2014-01-01

The presence of the G-spot (an assumed erotic sensitive area in the anterior wall of the vagina) remains controversial. We explored the histomorphological basis of the G-spot. Biopsies were drawn from a 12 o'clock direction in the distal- and proximal-third areas of the anterior vagina of 32 Chinese subjects. The total number of protein gene product 9.5-immunoreactive nerves and smooth muscle actin-immunoreactive blood vessels in each specimen was quantified using the avidin-biotin-peroxidase assay. Vaginal innervation was observed in the lamina propria and muscle layer of the anterior vaginal wall. The distal-third of the anterior vaginal wall had significantly richer small-nerve-fiber innervation in the lamina propria than the proximal-third (p = 0.000) and in the vaginal muscle layer (p = 0.006). There were abundant microvessels in the lamina propria and muscle layer, but no small vessels in the lamina propria and few in the muscle layer. Significant differences were noted in the number of microvessels when comparing the distal- with proximal-third parts in the lamina propria (p = 0.046) and muscle layer (p = 0.002). Significantly increased density of nerves and microvessels in the distal-third of the anterior vaginal wall could be the histomorphological basis of the G-spot. Distal anterior vaginal repair could disrupt the normal anatomy, neurovascular supply and function of the G-spot, and cause sexual dysfunction.

Three-layered architecture of the popliteal fascia that acts as a kinetic retinaculum for the hamstring muscles.

PubMed

Satoh, Masahiro; Yoshino, Hiroyuki; Fujimura, Akira; Hitomi, Jiro; Isogai, Sumio

2016-09-01

When patients report pain in the popliteal fossa upon knee extension, the pain is usually localized in the lower region of the popliteal fossa. However, some patients complain of pain in the upper region of the popliteal fossa as the knee is flexed, which motivated us to examine the role of the popliteal fascia as the retinaculum of the hamstring muscles. Thirty-four thighs from 19 Japanese cadavers were dissected. The popliteal fascia was defined as the single aponeurotic sheet covering the popliteal fossa. We found that the fascia acted as a three-layered retinaculum for the flexor muscles of the thigh and provided a secure route for neurovascular structures to the lower leg in any kinetic position of the knee joint. The superficial layer of the popliteal fascia covering the thigh was strongly interwoven with the epimysium of biceps femoris along its lateral aspect and with that of the semimembranosus along its medial aspect, ensuring that the flexor muscles remained in their correct positions. The intermediate layer arose from the medial side of biceps femoris and merged medially with the superficial layer. The profound layer stretched transversely between the biceps femoris and the semimembranosus. Moreover, we investigated the nerve distribution in the popliteal fascia using Sihler's staining and whole-mount immunostaining for neurofilaments. The three-layered fascia was constantly innervated by branches from the posterior femoral cutaneous or saphenous nerve. The nerves were closely related and distributed to densely packed collagen fibers in the superficial layer as free or encapsulated nerve endings, suggesting that the fascia is involved in pain in the upper region of the popliteal fossa.

Adenosine triphosphatase activity of cutaneous nerve fibers.

PubMed

Idé, C; Saito, T

1980-02-01

The histochemical study of Mg++-activated adenosine triphosphatase (Mg++-ATPase) activity was carried out on the peripheral nerves of mouse digital skin by light and electron microscopy. Under the light microscope, the ATPase activity was clearly demonstrated on the nerve fibers as a fine network in the subepidermal regions. Under the electron microscope, the reaction product of enzyme activity was located in the interspace between axolemma and the surrounding Schwann cells of the unmyelinated nerve fibers. No reaction product was observed in the space between the axolemma and the Schwann cells associated with myelinated nerve fibers. Demonstrable activity was absent at the nodes of Ranvier as well as on the para- and internodal regions of these myelinated axons. The part of the axolemma lacking a Schwann cell sheath failed to show a reaction product. The perineural epithelial cells surrounding the nerve fibers displayed reaction product in the caveolae. These results suggest a functional difference in the axon-Schwann interface of myelinated as compared to unmyelinated nerve fibers. The function of the perineural epithelial cell would be expected to be a regulatory one in transferring materials across the epithelium to keep the proper humoral environment around nerve fibers.

Influence of oculomotor nerve afferents on central endings of primary trigeminal fibers.

PubMed

Manni, E; Bortolami, R; Pettorossi, V E; Lucchi, M L; Callegari, E; Draicchio, F

1987-12-01

Painful fibers running in the third nerve and originating from the ophthalmic trigeminal area send their central projections at level of substantia gelatinosa of nucleus caudalis trigemini. The central endings of these fibers form axoaxonic synapses with trigeminal fibers entering the brain stem through the trigeminal root. The effect of electrical stimulation of the third nerve central stump on the central endings of trigeminal afferent fibers consists in an increased excitability, possibly resulting in a presynaptic inhibition. This inhibitory influence is due to both direct and indirect connections of the third nerve afferent fibers with the trigeminal ones.

Method to investigate temporal dynamics of ganglion and other retinal cells in the living human eye

NASA Astrophysics Data System (ADS)

Kurokawa, Kazuhiro; Liu, Zhuolin; Crowell, James; Zhang, Furu; Miller, Donald T.

2018-02-01

The inner retina is critical for visual processing, but much remains unknown about its neural circuitry and vulnerability to disease. A major bottleneck has been our inability to observe the structure and function of the cells composing these retinal layers in the living human eye. Here, we present a noninvasive method to observe both structural and functional information. Adaptive optics optical coherence tomography (AO-OCT) is used to resolve the inner retinal cells in all three dimensions and novel post processing algorithms are applied to extract structure and physiology down to the cellular level. AO-OCT captured the 3D mosaic of individual ganglion cell somas, retinal nerve fiber bundles of micron caliber, and microglial cells, all in exquisite detail. Time correlation analysis of the AO-OCT videos revealed notable temporal differences between the principal layers of the inner retina. The GC layer was more dynamic than the nerve fiber and inner plexiform layers. At the cellular level, we applied a customized correlation method to individual GCL somas, and found a mean time constant of activity of 0.57 s and spread of +/-0.1 s suggesting a range of physiological dynamics even in the same cell type. Extending our method to slower dynamics (from minutes to one year), time-lapse imaging and temporal speckle contrast revealed appendage and soma motion of resting microglial cells at the retinal surface.

Alterations of sympathetic nerve fibers in avascular necrosis of femoral head.

PubMed

Li, Deqiang; Liu, Peilai; Zhang, Yuankai; Li, Ming

2015-01-01

Avascular necrosis of the femoral head (ANFH) was mainly due to alterations of bone vascularity. And noradrenaline (NA), as the neurotransmitter of the sympathetic nervous system (SNS), leads to the vasoconstriction by activating its α-Receptor. This study was to explore the nerve fiber density of the femoral head in the rabbit model of ANFH. Twenty New Zealand white rabbits were used in this study. The rabbit model of ANFH was established by the injection of methylprednisolone acetate. The nerve fiber density and distribution in the femoral head was determined using an Olympus BH2 microscope. Significant fewer sympathetic nerve fibers was found in the ANFH intertrochanteric bone samples (P = 0.036) with osteonecrosis. The number of sympathetic nerve fibers was compared between the two groups. And less sympathetic nerve fibers were found in later stage ANFH samples in comparison with those of early stages. ANFH might be preceded by an inflammatory reaction, and an inflammatory response might lead to arthritic changes in tissue samples, which in turn reduces the number of sympathetic nerve fibers.

Corneal subbasal nerve fiber regeneration in myopic patients after laser in situ keratomileusis★

PubMed Central

Deng, Shijing; Wang, Mengmeng; Zhang, Fengju; Sun, Xuguang; Hou, Wenbo; Guo, Ning

2012-01-01

A total of 26 myopic patients (52 eyes) underwent laser in situ keratomileusis. In vivo confocal microscopy revealed that most of the regenerated corneal subbasal nerve fibers in the corneal flap originated from the stump of corneal subbasal nerve fibers outside the ablation zone and extended towards the center of the cornea in all patients. Meanwhile, new fibers were also found to directly regenerate from deep in the stroma in some cases. Approximately 94% of regenerated corneal subbasal nerve fibers (73/78 eyes) regrew vertically into the peripheral central 6-mm circle area 1 month after surgery, 78% (28/36 eyes) grew into the central 3–6 mm area at 2 months, and 23% into the central 3-mm circle area at 3 months. In addition, there was no significant difference in corneal subbasal nerve fiber regenerative capacity between the basic fibroblast growth factor group and the 20% (v/v) deproteinized extract of calf blood group. The majority of corneal subbasal nerve fiber regeneration occurred from the stump of corneal subbasal nerve fibers outside the corneal flap, and the remaining growth occurred deep within the stroma. PMID:25657693

Compromised Integrity of Central Visual Pathways in Patients With Macular Degeneration.

PubMed

Malania, Maka; Konrad, Julia; Jägle, Herbert; Werner, John S; Greenlee, Mark W

2017-06-01

Macular degeneration (MD) affects the central retina and leads to gradual loss of foveal vision. Although, photoreceptors are primarily affected in MD, the retinal nerve fiber layer (RNFL) and central visual pathways may also be altered subsequent to photoreceptor degeneration. Here we investigate whether retinal damage caused by MD alters microstructural properties of visual pathways using diffusion-weighted magnetic resonance imaging. Six MD patients and six healthy control subjects participated in the study. Retinal images were obtained by spectral-domain optical coherence tomography (SD-OCT). Diffusion tensor images (DTI) and high-resolution T1-weighted structural images were collected for each subject. We used diffusion-based tensor modeling and probabilistic fiber tractography to identify the optic tract (OT) and optic radiations (OR), as well as nonvisual pathways (corticospinal tract and anterior fibers of corpus callosum). Fractional anisotropy (FA) and axial and radial diffusivity values (AD, RD) were calculated along the nonvisual and visual pathways. Measurement of RNFL thickness reveals that the temporal circumpapillary retinal nerve fiber layer was significantly thinner in eyes with macular degeneration than normal. While we did not find significant differences in diffusion properties in nonvisual pathways, patients showed significant changes in diffusion scalars (FA, RD, and AD) both in OT and OR. The results indicate that the RNFL and the white matter of the visual pathways are significantly altered in MD patients. Damage to the photoreceptors in MD leads to atrophy of the ganglion cell axons and to corresponding changes in microstructural properties of central visual pathways.

Retinal Nerve Fiber Layer and Peripapillary Choroidal Thicknesses in Non-Glaucomatous Unilateral Optic Atrophy Compared with Unilateral Advanced Pseudoexfoliative Glaucoma.

PubMed

Kucukevcilioglu, Murat; Ayyildiz, Onder; Aykas, Seckin; Gokce, Gokcen; Koylu, Mehmet Talay; Ozgonul, Cem; Ozge, Gokhan; Mumcuoglu, Tarkan; Yumusak, Erhan

2017-02-01

To investigate retinal nerve fiber layer thickness (RNFL-T) and peripapillary choroidal thickness (PC-T) in non-glaucomatous optic atrophy (OA) patients in comparison with unaffected and control eyes, furthermore, to compare thickness profiles with unilateral pseudoexfoliative advanced glaucoma. Thirty-three eyes with OA (Group A), 33 unaffected fellow eyes (Group B), 25 right eyes of 25 control subjects (Group C), and 15 eyes with advanced glaucoma (Group D) were enrolled. RNFL-T was measured in six regions by spectral-domain optical coherence tomography. Enhanced depth imaging optical coherence tomography was obtained to evaluate PC-T in corresponding regions. RNFL-T was significantly lower in Group A than in Groups B and C globally and at all peripapillary regions (all p < 0.001). P-CT in Group A was significantly lower globally (p = 0.03) and in three regions (temporal, p = 0.001; temporal-superior, p = 0.01; and nasal-inferior, p = 0.037) versus Group C. However, it was significantly thinner than in Group B in all regions (temporal, p = 0.02; temporal-superior, p = 0.013; nasal-superior, p = 0.044; nasal, p = 0.02; nasal-inferior, p < 0.001; and temporal-inferior, p < 0.001) and globally (p < 0.001). In Group A RNFL-T (thicker superiorly and inferiorly; thinner temporally and nasally) and PC-T (superior > temporal > nasal > inferior) profiles were almost identical to that in unaffected fellow eyes and control eyes. However, Group D showed different patterns with less regional differences in RNFL-T, and the greatest value of PC-T in nasal quadrant. Besides retinal nerve fiber layer thinning, non-glaucomatous OA is associated with choroidal thinning. The RNFL-T and PC-T profiles in advanced glaucoma eyes differed from the common patterns seen among OA eyes, unaffected fellow eyes, and control eyes.

The effect of dentinal stimulation on pulp nerve function and pulp morphology in the dog.

PubMed

Hirvonen, T J; Närhi, M V

1986-11-01

The effect of dentinal stimulation on pulpal nerve responses and pulp morphology has been studied in the dog. Canine tooth (n = 25) dentin was stimulated by drilling, probing, and air-blasting for from two to five hours. Acid-etching was used to open dentinal tubules. All test teeth showed disruption of the odontoblast layer and its separation from the predentin; also, dislocation of odontoblast nuclei into dentinal tubules was found in most cases. Single-fiber (n = 14, conduction velocity = 24.3 +/- 7.4 (SD) m/s) recordings of the responses of canine tooth pulpal nerves to dentinal stimulation were made in ten of the stimulated teeth. No changes in the sensitivity of the nerves to dentinal stimulation could be detected. It is concluded that pulpal nerve function and morphological changes of the pulp are not clearly correlated. The condition of the dentin surface seems to be the important factor.

Corneal confocal microscopy detects small fiber neuropathy in CMT1A patients

PubMed Central

Tavakoli, Mitra; Marshall, Andy; Banka, Siddharth; Petropoulos, Ioannis N; Fadavi, Hassan; Kingston, Helen; Malik, Rayaz A

2012-01-01

Although unmyelinated nerve fibers are affected in CMT1A, they have not been studied in detail due to the invasive nature of the techniques needed to study them. We established alterations in C-fiber bundles of the cornea in patients with CMT1A using non-invasive corneal confocal microscopy (CCM). Twelve patients with CMT1A and twelve healthy control subjects underwent assessment of neuropathic symptoms and deficits, electrophysiology, quantitative sensory testing, corneal sensitivity and corneal confocal microscopy. Corneal sensitivity, corneal nerve fiber density, corneal nerve branch density, corneal nerve fiber length and corneal nerve fiber tortuosity were significantly reduced in CMT1A patients compared to controls. There was a significant correlation between corneal sensation and CCM parameters with the severity of painful neuropathic symptoms, cold and warm thresholds and median nerve CMAP amplitude. CCM demonstrates significant damage to C-fiber bundles, which relates to some measures of neuropathy in CMT1A patients. PMID:22996176

A Perturbation Based Decomposition of Compound-Evoked Potentials for Characterization of Nerve Fiber Size Distributions.

PubMed

Szlavik, Robert B

2016-02-01

The characterization of peripheral nerve fiber distributions, in terms of diameter or velocity, is of clinical significance because information associated with these distributions can be utilized in the differential diagnosis of peripheral neuropathies. Electro-diagnostic techniques can be applied to the investigation of peripheral neuropathies and can yield valuable diagnostic information while being minimally invasive. Nerve conduction velocity studies are single parameter tests that yield no detailed information regarding the characteristics of the population of nerve fibers that contribute to the compound-evoked potential. Decomposition of the compound-evoked potential, such that the velocity or diameter distribution of the contributing nerve fibers may be determined, is necessary if information regarding the population of contributing nerve fibers is to be ascertained from the electro-diagnostic study. In this work, a perturbation-based decomposition of compound-evoked potentials is proposed that facilitates determination of the fiber diameter distribution associated with the compound-evoked potential. The decomposition is based on representing the single fiber-evoked potential, associated with each diameter class, as being perturbed by contributions, of varying degree, from all the other diameter class single fiber-evoked potentials. The resultant estimator of the contributing nerve fiber diameter distribution is valid for relatively large separations in diameter classes. It is also useful in situations where the separation between diameter classes is small and the concomitant single fiber-evoked potentials are not orthogonal.

The Effect of Age on Optic Nerve Axon Counts, SDOCT Scan Quality, and Peripapillary Retinal Nerve Fiber Layer Thickness Measurements in Rhesus Monkeys

PubMed Central

Fortune, Brad; Reynaud, Juan; Cull, Grant; Burgoyne, Claude F.; Wang, Lin

2014-01-01

Purpose To evaluate the effect of age on optic nerve axon counts, spectral-domain optical coherence tomography (SDOCT) scan quality, and peripapillary retinal nerve fiber layer thickness (RNFLT) measurements in healthy monkey eyes. Methods In total, 83 healthy rhesus monkeys were included in this study (age range: 1.2–26.7 years). Peripapillary RNFLT was measured by SDOCT. An automated algorithm was used to count 100% of the axons and measure their cross-sectional area in postmortem optic nerve tissue samples (N = 46). Simulation experiments were done to determine the effects of optical changes on measurements of RNFLT. An objective, fully-automated method was used to measure the diameter of the major blood vessel profiles within each SDOCT B-scan. Results Peripapillary RNFLT was negatively correlated with age in cross-sectional analysis (P < 0.01). The best-fitting linear model was RNFLT(μm) = −0.40 × age(years) + 104.5 μm (R2 = 0.1, P < 0.01). Age had very little influence on optic nerve axon count; the result of the best-fit linear model was axon count = −1364 × Age(years) + 1,210,284 (R2 < 0.01, P = 0.74). Older eyes lost the smallest diameter axons and/or axons had an increased diameter in the optic nerve of older animals. There was an inverse correlation between age and SDOCT scan quality (R = −0.65, P < 0.0001). Simulation experiments revealed that approximately 17% of the apparent cross-sectional rate of RNFLT loss is due to reduced scan quality associated with optical changes of the aging eye. Another 12% was due to thinning of the major blood vessels. Conclusions RNFLT declines by 4 μm per decade in healthy rhesus monkey eyes. This rate is approximately three times faster than loss of optic nerve axons. Approximately one-half of this difference is explained by optical degradation of the aging eye reducing SDOCT scan quality and thinning of the major blood vessels. Translational Relevance Current models used to predict retinal ganglion cell losses should be reconsidered. PMID:24932430

Identification of the origin of adrenergic and cholinergic nerve fibers within the superior hypogastric plexus of the human fetus

PubMed Central

Zaitouna, Mazen; Alsaid, Bayan; Diallo, Djibril; Benoit, Gérard; Bessede, Thomas

2013-01-01

Nerve fibers contributing to the superior hypogastric plexus (SHP) and the hypogastric nerves (HN) are currently considered to comprise an adrenergic part of the autonomic nervous system located between vertebrae (T1 and L2), with cholinergic aspects originating from the second to fourth sacral spinal segments (S2, S3 and S4). The aim of this study was to identify the origin and the nature of the nerve fibers within the SHP and the HN, especially the cholinergic fibers, using computer-assisted anatomic dissection (CAAD). Serial histological sections were performed at the level of the lumbar spine and pelvis in five human fetuses between 14 and 30 weeks of gestation. Sections were treated with histological staining [hematoxylin-eosin (HE) and Masson's trichrome (TriM)] and with immunohistochemical methods to detect nerve fibers (anti-S100), adrenergic fibers (anti-TH), cholinergic fibers (anti-VAChT) and nitrergic fibers (anti-nNOS). The sections were then digitalized using a high-resolution scanner and the 3D images were reconstructed using winsurf software. These experiments revealed the coexistence of adrenergic and cholinergic fibers within the SHP and the HNs. One-third of these cholinergic fibers were nitrergic fibers [anti-VACHT (+)/anti-NOS (+)] and potentially pro-erectile, while the others were non-nitrergic [anti-VACHT (+)/anti-NOS (−)]. We found these cholinergic fibers arose from the lumbar nerve roots. This study described the nature of the SHP nerve fibers which gives a better understanding of the urinary and sexual dysfunctions after surgical injuries. PMID:23668336

Human Lymphatic Mesenteric Vessels: Morphology and Possible Function of Aminergic and NPY-ergic Nerve Fibers.

PubMed

D'Andrea, Vito; Panarese, Alessandra; Taurone, Samanta; Coppola, Luigi; Cavallotti, Carlo; Artico, Marco

2015-09-01

The lymphatic vessels have been studied in different organs from a morphological to a clinical point of view. Nevertheless, the knowledge of the catecholaminergic control of the lymphatic circulation is still incomplete. The aim of this work is to study the presence and distribution of the catecholaminergic and NPY-ergic nerve fibers in the whole wall of the human mesenteric lymphatic vessels in order to obtain knowledge about their morphology and functional significance. The following experimental procedures were performed: 1) drawing of tissue containing lymphatic vessels; 2) cutting of tissue; 3) staining of tissue; 4) staining of nerve fibers; 5) histofluorescence microscopy for the staining of catecholaminergic nerve fibers; 6) staining of neuropeptide Y like-immune reactivity; 7) biochemical assay of proteins; 8) measurement of noradrenaline; 9) quantitative analysis of images; 10) statistical analysis of data. Numerous nerve fibers run in the wall of lymphatic vessels. Many of them are catecholaminergic in nature. Some nerve fibers are NPY-positive. The biochemical results on noradrenaline amounts are in agreement with morphological results on catecholaminergic nerve fibers. Moreover, the morphometric results, obtained by the quantitative analysis of images and the subsequent statistical analysis of data, confirm all our morphological and biochemical data. The knowledge of the physiological or pathological mechanism regulating the functions of the lymphatic system is incomplete. Nevertheless the catecholaminergic nerve fibers of the human mesenteric lymphatic vessels come from the adrenergic periarterial plexuses of the mesenterial arterial bed. NPY-ergic nerve fibers may modulate the microcirculatory mesenterial bed in different pathological conditions.

Diffusion tensor imaging of the optic tracts in multiple sclerosis: association with retinal thinning and visual disability.

PubMed

Dasenbrock, Hormuzdiyar H; Smith, Seth A; Ozturk, Arzu; Farrell, Sheena K; Calabresi, Peter A; Reich, Daniel S

2011-04-01

Visual disability is common in multiple sclerosis, but its relationship to abnormalities of the optic tracts remains unknown. Because they are only rarely affected by lesions, the optic tracts may represent a good model for assessing the imaging properties of normal-appearing white matter in multiple sclerosis. Whole-brain diffusion tensor imaging was performed on 34 individuals with multiple sclerosis and 26 healthy volunteers. The optic tracts were reconstructed by tractography, and tract-specific diffusion indices were quantified. In the multiple-sclerosis group, peripapillary retinal nerve-fiber-layer thickness and total macular volume were measured by optical coherence tomography, and visual acuity at 100%, 2.5%, and 1.25% contrast was examined. After adjusting for age and sex, optic-tract mean and perpendicular diffusivity were higher (P=.002) in multiple sclerosis. Lower optic-tract fractional anisotropy was correlated with retinal nerve-fiber-layer thinning (r=.51, P=.003) and total-macular-volume reduction (r=.59, P=.002). However, optic-tract diffusion indices were not specifically correlated with visual acuity or with their counterparts in the optic radiation. Optic-tract diffusion abnormalities are associated with retinal damage, suggesting that both may be related to optic-nerve injury, but do not appear to contribute strongly to visual disability in multiple sclerosis. Copyright © 2010 by the American Society of Neuroimaging.

Diffusion Tensor Imaging of the Optic Tracts in Multiple Sclerosis: Association with Retinal Thinning and Visual Disability

PubMed Central

Dasenbrock, Hormuzdiyar H.; Smith, Seth A.; Ozturk, Arzu; Farrell, Sheena K.; Calabresi, Peter A.; Reich, Daniel S.

2009-01-01

Background and purpose Visual disability is common in multiple sclerosis, but its relationship to abnormalities of the optic tracts remains unknown. Because they are only rarely affected by lesions, the optic tracts may represent a good model for assessing the imaging properties of normal-appearing white matter in multiple sclerosis. Methods Whole-brain diffusion tensor imaging was performed on 34 individuals with multiple sclerosis and 26 healthy volunteers. The optic tracts were reconstructed by tractography, and tract-specific diffusion indices were quantified. In the multiple-sclerosis group, peripapillary retinal nerve-fiber-layer thickness and total macular volume were measured by optical coherence tomography, and visual acuity at 100%, 2.5%, and 1.25% contrast was examined. Results After adjusting for age and sex, optic-tract mean and perpendicular diffusivity were higher (p=0.002) in multiple sclerosis. Lower optic-tract fractional anisotropy was correlated with retinal nerve-fiber-layer thinning (r=0.51, p=0.003) and total-macular-volume reduction (r=0.59, p=0.002). However, optic-tract diffusion indices were not specifically correlated with visual acuity or with their counterparts in the optic radiation. Conclusions Optic-tract diffusion abnormalities are associated with retinal damage, suggesting that both may be related to optic-nerve injury, but do not appear to contribute strongly to visual disability in multiple sclerosis. PMID:20331501

Nerve Fiber Flux Analysis Using Wide-Field Swept-Source Optical Coherence Tomography.

PubMed

Tan, Ou; Liu, Liang; Liu, Li; Huang, David

2018-02-01

To devise a method to quantify nerve fibers over their arcuate courses over an extended peripapillary area using optical coherence tomography (OCT). Participants were imaged with 8 × 8-mm volumetric OCT scans centered at the optic disc. A new quantity, nerve fiber flux (NFF), represents the cross-sectional area transected perpendicular to the nerve fibers. The peripapillary area was divided into 64 tracks with equal flux. An iterative algorithm traced the trajectory of the tracks assuming that the relative distribution of the NFF was conserved with compensation for fiber connections to ganglion cells on the macular side. Average trajectory was averaged from normal eyes and use to calculate the NFF maps for glaucomatous eyes. The NFF maps were divided into eight sectors that correspond to visual field regions. There were 24 healthy and 10 glaucomatous eyes enrolled. The algorithm converged on similar patterns of NFL tracks for all healthy eyes. In glaucomatous eyes, NFF correlated with visual field sensitivity in the arcuate sectors (Spearman ρ = 0.53-0.62). Focal nerve fiber loss in glaucomatous eyes appeared as uniform tracks of NFF defects that followed the expected arcuate fiber trajectory. Using an algorithm based on the conservation of flux, we derived nerve fiber trajectories in the peripapillary area. The NFF map is useful for the visualization of focal defects and quantification of sector nerve fiber loss from wide-area volumetric OCT scans. NFF provides a cumulative measure of volumetric loss along nerve fiber tracks and could improve the detection of focal glaucoma damage.

Corneal and Retinal Neuronal Degeneration in Early Stages of Diabetic Retinopathy.

PubMed

Srinivasan, Sangeetha; Dehghani, Cirous; Pritchard, Nicola; Edwards, Katie; Russell, Anthony W; Malik, Rayaz A; Efron, Nathan

2017-12-01

To examine the neuronal structural integrity of cornea and retina as markers for neuronal degeneration in nonproliferative diabetic retinopathy (NPDR). Participants were recruited from the broader Brisbane community, Queensland, Australia. Two hundred forty-one participants (187 with diabetes and 54 nondiabetic controls) were examined. Diabetic retinopathy (DR) was graded according to the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Corneal nerve fiber length (CNFL), corneal nerve branch density (CNBD), corneal nerve fiber tortuosity (CNFT), full retinal thickness, retinal nerve fiber layer (RNFL), ganglion cell complex (GCC), focal (FLV) and global loss volumes (GLV), hemoglobin A1c (HbA1c), nephropathy, neuropathy, and cardiovascular measures were examined. The central zone (P = 0.174), parafoveal thickness (P = 0.090), perifovea (P = 0.592), RNFL (P = 0.866), GCC (P = 0.798), and GCC GLV (P = 0.338) did not differ significantly between the groups. In comparison to the control group, those with very mild NPDR and those with mild NPDR had significantly higher focal loss in GCC volume (P = 0.036). CNFL was significantly lower in those with mild NPDR (P = 0.004) in comparison to the control group and those with no DR. The CNBD (P = 0.094) and CNFT (P = 0.458) did not differ between the groups. Both corneal and retinal neuronal degeneration may occur in early stages of diabetic retinopathy. Further studies are required to examine these potential markers for neuronal degeneration in the absence of clinical signs of DR.

Three-dimensional retinal imaging with high-speed ultrahigh-resolution optical coherence tomography.

PubMed

Wojtkowski, Maciej; Srinivasan, Vivek; Fujimoto, James G; Ko, Tony; Schuman, Joel S; Kowalczyk, Andrzej; Duker, Jay S

2005-10-01

To demonstrate high-speed, ultrahigh-resolution, 3-dimensional optical coherence tomography (3D OCT) and new protocols for retinal imaging. Ultrahigh-resolution OCT using broadband light sources achieves axial image resolutions of approximately 2 microm compared with standard 10-microm-resolution OCT current commercial instruments. High-speed OCT using spectral/Fourier domain detection enables dramatic increases in imaging speeds. Three-dimensional OCT retinal imaging is performed in normal human subjects using high-speed ultrahigh-resolution OCT. Three-dimensional OCT data of the macula and optic disc are acquired using a dense raster scan pattern. New processing and display methods for generating virtual OCT fundus images; cross-sectional OCT images with arbitrary orientations; quantitative maps of retinal, nerve fiber layer, and other intraretinal layer thicknesses; and optic nerve head topographic parameters are demonstrated. Three-dimensional OCT imaging enables new imaging protocols that improve visualization and mapping of retinal microstructure. An OCT fundus image can be generated directly from the 3D OCT data, which enables precise and repeatable registration of cross-sectional OCT images and thickness maps with fundus features. Optical coherence tomography images with arbitrary orientations, such as circumpapillary scans, can be generated from 3D OCT data. Mapping of total retinal thickness and thicknesses of the nerve fiber layer, photoreceptor layer, and other intraretinal layers is demonstrated. Measurement of optic nerve head topography and disc parameters is also possible. Three-dimensional OCT enables measurements that are similar to those of standard instruments, including the StratusOCT, GDx, HRT, and RTA. Three-dimensional OCT imaging can be performed using high-speed ultrahigh-resolution OCT. Three-dimensional OCT provides comprehensive visualization and mapping of retinal microstructures. The high data acquisition speeds enable high-density data sets with large numbers of transverse positions on the retina, which reduces the possibility of missing focal pathologies. In addition to providing image information such as OCT cross-sectional images, OCT fundus images, and 3D rendering, quantitative measurement and mapping of intraretinal layer thickness and topographic features of the optic disc are possible. We hope that 3D OCT imaging may help to elucidate the structural changes associated with retinal disease as well as improve early diagnosis and monitoring of disease progression and response to treatment.

Scanning Laser Polarimetry and Optical Coherence Tomography for Detection of Retinal Nerve Fiber Layer Defects

PubMed Central

Oh, Jong-Hyun

2009-01-01

Purpose To compare the ability of scanning laser polarimetry with variable corneal compensation (GDx-VCC) and Stratus optical coherence tomography (OCT) to detect photographic retinal nerve fiber layer (RNFL) defects. Methods This retrospective cross-sectional study included 45 eyes of 45 consecutive glaucoma patients with RNFL defects in red-free fundus photographs. The superior and inferior temporal quadrants in each eye were included for data analysis separately. The location and presence of RNFL defects seen in red-free fundus photographs were compared with those seen in GDx-VCC deviation maps and OCT RNFL analysis maps for each quadrant. Results Of the 90 quadrants (45 eyes), 31 (34%) had no apparent RNFL defects, 29 (32%) had focal RNFL defects, and 30 (33%) had diffuse RNFL defects in red-free fundus photographs. The highest agreement between GDx-VCC and red-free photography was 73% when we defined GDx-VCC RNFL defects as a cluster of three or more color-coded squares (p<5%) along the traveling line of the retinal nerve fiber in the GDx-VCC deviation map (kappa value, 0.388; 95% confidence interval (CI), 0.195 to 0.582). The highest agreement between OCT and red-free photography was 85% (kappa value, 0.666; 95% CI, 0.506 to 0.825) when a value of 5% outside the normal limit for the OCT analysis map was used as a cut-off value for OCT RNFL defects. Conclusions According to the kappa values, the agreement between GDx-VCC deviation maps and red-free photography was poor, whereas the agreement between OCT analysis maps and red-free photography was good. PMID:19794943

Effect of cataract surgery on retinal nerve fiber layer thickness parameters using scanning laser polarimetry (GDxVCC)

PubMed Central

Dada, Tanuj; Behera, Geeta; Agarwal, Anand; Kumar, Sanjeev; Sihota, Ramanjit; Panda, Anita

2010-01-01

Purpose: To study the effect of cataract extraction on the retinal nerve fiber layer (RNFL) thickness, and assessment by scanning laser polarimetry (SLP), with variable corneal compensation (GDx VCC), at the glaucoma service of a tertiary care center in North India. Materials and Methods: Thirty-two eyes of 32 subjects were enrolled in the study. The subjects underwent RNFL analysis by SLP (GDx VCC) before undergoing phacoemulsification cataract extraction with intraocular lens (IOL) implantation (Acrysof SA 60 AT) four weeks following cataract surgery. The RNFL thickness parameters evaluated both before and after surgery included temporal, superior, nasal, inferior, temporal (TSNIT) average, superior average, inferior average, and nerve fiber index (NFI). Results: The mean age of subjects was 57.6 ± 11.7 years (18 males, 14 females). Mean TSNIT average thickness (μm) pre- and post-cataract surgery was 49.2 ± 14.1 and 56.5 ± 7.6 (P = 0.001). There was a statistically significant increase in RNFL thickness parameters (TSNIT average, superior average, and inferior average) and decrease in NFI post-cataract surgery as compared to the baseline values. Mean NFI pre- and post-cataract surgery was 41.3 ± 15.3 and 21.6 ± 11.8 (P = 0.001). Conclusions: Measurement of RNFL thickness parameters by scanning laser polarimetry is significantly altered following cataract surgery. Post the cataract surgery, a new baseline needs to be established for assessing the longitudinal follow-up of a glaucoma patient. The presence of cataract may lead to an underestimation of the RNFL thickness, and this should be taken into account when analyzing progression in a glaucoma patient. PMID:20689193

A simple immunofluorescence technique for simultaneous visualization of mast cells and nerve fibers reveals selectivity and hair cycle--dependent changes in mast cell--nerve fiber contacts in murine skin.

PubMed

Botchkarev, V A; Eichmüller, S; Peters, E M; Pietsch, P; Johansson, O; Maurer, M; Paus, R

1997-04-01

Close contacts between mast cells (MC) and nerve fibers have previously been demonstrated in normal and inflamed skin by light and electron microscopy. A key step for any study in MC-nerve interactions in situ is to simultaneously visualize both communication partners, preferably with the option of double labelling the nerve fibers. For this purpose, we developed the following triple-staining technique. After paraformaldehyde-picric acid perfusion fixation, cryostat sections of back skin from C57BL/6 mice were incubated with a primary rat monoclonal antibody to substance P (SP), followed by incubation with a secondary goat-anti-rat TRITC-conjugated IgG. A rabbit antiserum to CGRP was then applied, followed by a secondary goat-anti-rabbit FITC-conjugated IgG. MCs were visualized by incubation with AMCA-labelled avidin, or (for a more convenient quantification of close MC-nerve fiber contacts) with a mixture of TRITC- and FITC-labelled avidins. Using this simple, novel covisualization method, we were able to show that MC-nerve associations in mouse skin are, contrary to previous suggestions, highly selective for nerve fiber types, and that these interactions are regulated in a hair cycle-dependent manner: in telogen and early anagen skin, MCs preferentially contacted CGRP-immunoreactive (IR) or SP/CGRP-IR double-labelled nerve fibers. Compared with telogen values, there was a significant increase in the number of close contacts between MCs and tyrosine hydroxylase-IR fibers during late anagen, and between MCs and peptide histidine-methionine-IR and choline acetyl transferase-IR fibers during catagen.

Motor unit and muscle fiber type grouping after peripheral nerve injury in the rat.

PubMed

Gordon, Tessa; de Zepetnek, Joanne E Totosy

2016-11-01

Muscle unit (MU) fibers innervated by one motoneuron and corresponding muscle fiber types are normally distributed in a mosaic. We asked whether, 4-8months after common peroneal nerve transection and random surgical alignment of nerve stumps in rat tibialis anterior muscles 1) reinnervated MU muscle and muscle fiber type clumping is invariant and 2) slow and fast motoneurons regenerate their nerve fibers within original endoneurial pathways. MU contractile forces were recorded in vivo, the MUs classified into types according to their contractile speed and fatigability, and one MU subjected to alternate exhaustive stimulation-recovery cycles to deplete glycogen for histochemical MU fiber recognition and enumeration, and muscle fiber typing. MU muscle fibers occupied defined territories whose size increased with MU force and muscle fiber numbers in normal and reinnervated muscles. The reinnervated MU muscle fiber territories were significantly smaller, the fibers clumped within 1-3 groups in 90% of the MUs, and each fiber lying adjacent to another significantly more frequently. Most reinnervated slow muscle fibers were normally located in the deep muscle compartment but substantial numbers were located abnormally in the superficial compartment. Our findings that well reinnervated muscle fibers clump in small muscles contrast with our earlier findings of clumping in large muscles only when reinnervated MU numbers were significantly reduced. We conclude that fiber type clumping is predictive of muscle reinnervation in small but not large muscles. In the latter muscles, clumping is more indicative of sprouting after partial nerve injuries than of muscle reinnervation after complete nerve injuries. Copyright © 2016 Elsevier Inc. All rights reserved.

Identification of a novel mutation in the PTCH gene in a patient with Gorlin-Goltz syndrome with unusual ocular disorders.

PubMed

Romano, Mary; Iacovello, Daniela; Cascone, Nikhil C; Contestabile, Maria Teresa

2011-01-01

To document the clinical, functional, and in vivo microanatomic characteristics of a patient with Gorlin-Goltz syndrome with a novel nonsense mutation in PTCH (patched). Optical coherence tomography (OCT), fluorescein angiography, electrophysiologic testing, visual field, magnetic resonance imaging, and mutation screening of PTCH gene. Visual acuity was 20/20 in the right eye and 20/25 in the left. Fundus examination revealed myelinated nerve fibers in the left eye and bilateral epiretinal membranes with lamellar macular hole also documented with macular OCT. A reduction of the retinal nerve fiber layers in both eyes was found with fiber nervous OCT. Fluorescein angiography showed bilaterally foveal hyperfluorescence and the visual field revealed inferior hemianopia in the right eye. Pattern visual evoked potentials registered a reduction of amplitude in both eyes and latency was delayed in the left eye. Pattern electroretinogram showed a reduction in P50 and N95 peak time and a delay in P50 peak time in the left eye. Flash electroretinogram was reduced in rod response, maximal response, and oscillatory potentials in both eyes. Cone response was normal and 30-Hz flicker was slightly reduced in both eyes. Mutation screening identified a novel nonsense mutation in PTCH. A novel nonsense mutation in the PTCH gene was found. We report the occurrence of epiretinal membranes and the persistence of myelinated nerve fibers. Electrophysiologic and visual field alterations, supporting a neuroretinal dysfunction, were also documented.

Distribution of CGRP and TRPV2 in Human Paranasal Sinuses.

PubMed

Sato, Tadasu; Sasahara, Nobuyuki; Kanda, Noriyuki; Sasaki, Yu; Yamaguma, Yu; Kokubun, Souichi; Yajima, Takehiro; Ichikawa, Hiroyuki

2017-01-01

Immunohistochemistry for protein gene product 9.5 (PGP 9.5), calcitonin gene-related peptide (CGRP) and the transient receptor potential cation channel subfamily V member 2 (TRPV2) was performed on human paranasal sinuses. It was found that in the paranasal sinuses, mucous membranes contain PGP 9.5-immunoreactive (PGP 9.5-IR) nerve fibers. Such nerve fibers terminated around large blood vessels as fine varicosities. Isolated PGP 9.5-IR nerve fibers were scattered beneath the epithelium. Glandular tissues were also innervated by PGP 9.5-IR nerve fibers. These fibers were numerous in the maxillary and ethmoid sinuses, and relatively rare in the frontal and sphenoid sinuses. CGRP-IR nerve fibers were common in the maxillary sinus whereas TRPV2-IR nerve fibers were abundant in the ethmoid sinus. They were located around large blood vessels in the lamina propria. Many subepithelial nerve fibers contained TRPV2 immunoreactivity in the ethmoid sinus. CGRP- and TRPV2-IR nerve fibers were very infrequent in the frontal and sphenoid sinuses. In the human trigeminal ganglion (TG), sensory neurons contained CGRP or TRPV2 immunoreactivity. CGRP-IR TG neurons were more common than TRPV2-IR TG neurons. CGRP-IR TG neurons were of various cell body sizes, whereas TRPV2-IR TG neurons were mostly medium-to-large. In addition, human spinal and principal trigeminal sensory nuclei contained abundant CGRP- and TRPV2-IR varicosities. This study indicates that CGRP- and TRPV2-containing TG neurons probably innervate the paranasal sinus mucosae, and project into spinal and principal trigeminal sensory nuclei. © 2016 S. Karger AG, Basel.

Specific paucity of unmyelinated C-fibers in cutaneous peripheral nerves of the African naked-mole rat: comparative analysis using six species of Bathyergidae.

PubMed

St John Smith, Ewan; Purfürst, Bettina; Grigoryan, Tamara; Park, Thomas J; Bennett, Nigel C; Lewin, Gary R

2012-08-15

In mammalian peripheral nerves, unmyelinated C-fibers usually outnumber myelinated A-fibers. By using transmission electron microscopy, we recently showed that the saphenous nerve of the naked mole-rat (Heterocephalus glaber) has a C-fiber deficit manifested as a substantially lower C:A-fiber ratio compared with other mammals. Here we determined the uniqueness of this C-fiber deficit by performing a quantitative anatomical analysis of several peripheral nerves in five further members of the Bathyergidae mole-rat family: silvery (Heliophobius argenteocinereus), giant (Fukomys mechowii), Damaraland (Fukomys damarensis), Mashona (Fukomys darlingi), and Natal (Cryptomys hottentotus natalensis) mole-rats. In the largely cutaneous saphenous and sural nerves, the naked mole-rat had the lowest C:A-fiber ratio (∼1.5:1 compared with ∼3:1), whereas, in nerves innervating both skin and muscle (common peroneal and tibial) or just muscle (lateral/medial gastrocnemius), this pattern was mostly absent. We asked whether lack of hair follicles alone accounts for the C-fiber paucity by using as a model a mouse that loses virtually all its hair as a consequence of conditional deletion of the β-catenin gene in the skin. These β-catenin loss-of function mice (β-cat LOF mice) displayed only a mild decrease in C:A-fiber ratio compared with wild-type mice (4.42 compared with 3.81). We suggest that the selective cutaneous C-fiber deficit in the cutaneous nerves of naked mole-rats is unlikely to be due primarily to lack of skin hair follicles. Possible mechanisms contributing to this unique peripheral nerve anatomy are discussed. Copyright © 2012 Wiley Periodicals, Inc.

Specific Paucity of Unmyelinated C-Fibers in Cutaneous Peripheral Nerves of the African Naked-Mole Rat: Comparative Analysis Using Six Species of Bathyergidae

PubMed Central

Smith, Ewan S; Purfürst, Bettina; Grigoryan, Tamara; Park, Thomas J; Bennett, Nigel C; Lewin, Gary R

2012-01-01

In mammalian peripheral nerves, unmyelinated C-fibers usually outnumber myelinated A-fibers. By using transmission electron microscopy, we recently showed that the saphenous nerve of the naked mole-rat (Heterocephalus glaber) has a C-fiber deficit manifested as a substantially lower C:A-fiber ratio compared with other mammals. Here we determined the uniqueness of this C-fiber deficit by performing a quantitative anatomical analysis of several peripheral nerves in five further members of the Bathyergidae mole-rat family: silvery (Heliophobius argenteocinereus), giant (Fukomys mechowii), Damaraland (Fukomys damarensis), Mashona (Fukomys darlingi), and Natal (Cryptomys hottentotus natalensis) mole-rats. In the largely cutaneous saphenous and sural nerves, the naked mole-rat had the lowest C:A-fiber ratio (∼1.5:1 compared with ∼3:1), whereas, in nerves innervating both skin and muscle (common peroneal and tibial) or just muscle (lateral/medial gastrocnemius), this pattern was mostly absent. We asked whether lack of hair follicles alone accounts for the C-fiber paucity by using as a model a mouse that loses virtually all its hair as a consequence of conditional deletion of the β-catenin gene in the skin. These β-catenin loss-of function mice (β-cat LOF mice) displayed only a mild decrease in C:A-fiber ratio compared with wild-type mice (4.42 compared with 3.81). We suggest that the selective cutaneous C-fiber deficit in the cutaneous nerves of naked mole-rats is unlikely to be due primarily to lack of skin hair follicles. Possible mechanisms contributing to this unique peripheral nerve anatomy are discussed. J. Comp. Neurol. 520:2785–2803, 2012. © 2012 Wiley Periodicals, Inc. PMID:22528859

Mu-opiate receptor and Beta-endorphin expression in nerve endings and keratinocytes in human skin.

PubMed

Bigliardi-Qi, M; Sumanovski, L T; Büchner, S; Rufli, T; Bigliardi, P L

2004-01-01

We have previously shown that human epidermal keratinocytes express a functionally active micro-opiate receptor, which adds a new dimension to the recently developed research in neuroimmunodermatology and neurogenic inflammation in skin diseases. Human keratinocytes specifically bind and also produce beta-endorphin, the endogenous micro-opiate receptor ligand. Using confocal imaging microscopy, we could now demonstrate that micro-opiate receptors are not only expressed in keratinocytes, but also on unmyelinated peripheral nerve fibers in the dermis and epidermis. Some of the peripheral nerve fibers also express the ligand beta-endorphin. The keratinocytes positive for beta-endorphin staining are clustered around the terminal ends of the unmyelinated nerve fibers. Therefore the opiate receptor system seems to be crucial in the direct communication between nerves and skin. The keratinocytes can influence the unmyelinated nerve fibers in the epidermis directly via secreting beta-endorphin. On the other hand, nerve fibers can also secrete beta-endorphin and influence the migration, differentiation and probably also the cytokine production pattern of keratinocytes.

Age-related ultrastructural and monoamine oxidase changes in the rat optic nerve.

PubMed

Taurone, S; Ripandelli, G; Minni, A; Lattanzi, R; Miglietta, S; Pepe, N; Fumagalli, L; Micera, A; Pastore, F S; Artico, M

2016-01-01

The aim of this paper is to study the morphology and the distribution of the monoamine oxidase enzymatic system in the optic nerve of 4 month-old Wistar (young) and 28 month-old Wistar (old) rats. The optic nerve was harvested from 20 young and old rats. The segment of optic nerve was divided longitudinally into two pieces, each 0.1 mm in length. The first piece was used for transmission electron microscopy. The second piece was stained with histochemical reaction for monoamine oxidase. The agerelated changes in the optic nerve of rats include micro-anatomical details, ultrastructure and monoamine oxidase histochemical staining. A strong decrease of the thin nerve fibers and a swelling of the thick ones can be observed in optic nerve fibers of old rats. Increased monoamine oxidase histochemical staining of the optic nerve of aged rats is well demonstrated. The increase of meningeal shealth and the decrease of thin nerve fibers of the optic nerve in old rats are well documented. Morphological, ultrastructural and histochemical changes observed in optic nerve fibers of the old rats show a close relation with aging.

Holographic line field en-face OCT with digital adaptive optics in the retina in vivo.

PubMed

Ginner, Laurin; Schmoll, Tilman; Kumar, Abhishek; Salas, Matthias; Pricoupenko, Nastassia; Wurster, Lara M; Leitgeb, Rainer A

2018-02-01

We demonstrate a high-resolution line field en-face time domain optical coherence tomography (OCT) system using an off-axis holography configuration. Line field en-face OCT produces high speed en-face images at rates of up to 100 Hz. The high frame rate favors good phase stability across the lateral field-of-view which is indispensable for digital adaptive optics (DAO). Human retinal structures are acquired in-vivo with a broadband light source at 840 nm, and line rates of 10 kHz to 100 kHz. Structures of different retinal layers, such as photoreceptors, capillaries, and nerve fibers are visualized with high resolution of 2.8 µm and 5.5 µm in lateral directions. Subaperture based DAO is successfully applied to increase the visibility of cone-photoreceptors and nerve fibers. Furthermore, en-face Doppler OCT maps are generated based on calculating the differential phase shifts between recorded lines.

Anatomy and histology of the transverse humeral ligament.

PubMed

Snow, Brian J; Narvy, Steven J; Omid, Reza; Atkinson, Roscoe D; Vangsness, C Thomas

2013-10-01

The classic literature describes the transverse humeral ligament (THL) as a distinct anatomic structure with a role in biceps tendon stability; however, recent literature suggests that it is not a distinct anatomic structure. The purpose of this study was to evaluate the gross and microscopic anatomy of the THL, including a specific investigation of the histology of this ligament. Thirty frozen, embalmed cadaveric specimens were dissected to determine the gross anatomy of the THL. Seven specimens were evaluated histologically for the presence of mechanoreceptors and free nerve endings. Two tissue layers were identified in the area described as the THL. In the deep layer, fibers of the subscapularis tendon were found to span the bicipital groove with contributions from the coracohumeral ligament and the supraspinatus tendon. Superficial to this layer was a fibrous fascial covering consisting of distinct bands of tissue. Neurohistology staining revealed the presence of free nerve endings but no mechanoreceptors. This study's findings demonstrate that the THL is a distinct structure continuous with the rotator cuff tendons and the coracohumeral ligament. The finding of free nerve endings in the THL suggests a potential role as a shoulder pain generator. Copyright 2013, SLACK Incorporated.

[The eye and nutrition].

PubMed

Amemiya, T

1999-12-01

To examine the effect of vitamins and trace elements on ocular tissue. Rats or mice were fed diets deficient in the trace elements Zn, Cu, Mn, Se, Mg, and Cr or in vitamins A, B12, C, and E. In some rats Al and vitamin A were injected in excessive amounts. We studied the conjunctiva, cornea, retina, and optic nerve with a light microscope, transmission and scanning electron microscopes, an energy dispersive X-ray analyser, and an ion microscope. Histochemical, cytochemical, and immunohistochemical techniques were applied to the pathological specimens. Deficiencies of Zn, Cu, Mn, and vitamins A, C and E caused a loss of goblet cells in the conjunctiva and a prominent decrease of microvilli and microplicae in the conjunctiva and cornea. The elements in the goblet cells were changed in these conditions. In addition, epithelial cells showed poor fibrous development and abnormal distribution of chromatin in the nucleus. Zn, Cu, Mn, and vitamins A and E deficiencies caused photoreceptor cells to degenerate and disappear. Se deficiency reduced the horizontal and amacrine cells. Vitamin B12 deficiency reduced nerve fibers in the nerve fiber layer of the retina. Mg deficiency induced multifocal necrosis in the retinal pigment epithelium and apoptotic nuclear changes in the photoreceptor cells. Cr deficiency showed abnormal phagocytosis of the photoreceptor outer segment discs in the retinal pigment epithelium. Vitamin B12 was found to be related to the circadian rhythm in the retina. Deficiencies of Zn, Cu, Mn, and vitamins A, B12, and E induced degeneration and disappearance of myelin lamellae in the myelinated optic nerve fibers. In hypervitaminosis A, lipid droplets appeared in the retinal pigment epithelium and alcohol dehydrogenase disappeared in the retinal pigment epithelium and photoreceptor outer segments. Excessive Al was toxic to the retina, which showed disappearance of photoreceptor cells. Al deposits were seen in dendrites and neurons in the outer plexiform layer. Zn seemed to be necessary for corneal epithelial cell wound healing. Trace elements usually are contained in enzymes, which have many metabolic functions. They are related to synthesis and breakdown of many substances. Some trace elements such as Zn, Cu, Mn, and Se and vitamins including vitamins A, C, and E prevent peroxidation of lipids. Some vitamins have an affinity for specific tissues such as epithelial cells, nerve fibers, and neuronal cells and are needed for cell differentiation, development, and maintenance. Cu, Zn, Mn, Se, Mg, and Cr and vitamins A, B12, C, and E are necessary for maintenance of cellular structure and metabolism.

The eye and nutrition

PubMed

Amemiya

2000-05-01

Purpose: To examine the effect of vitamins and trace elements on ocular tissue.Materials and Methods: Rats or mice were fed diets deficient in the trace elements Zn, Cu, Mn, Se, Mg, and Cr or in vitamins A, B(12), C, and E. In some rats Al and vitamin A were injected in excessive amounts. We studied the conjunctiva, cornea, retina, and optic nerve with a light microscope, transmission and scanning electron microscopes, an energy dispersive X-ray analyzer, and an ion microscope. Histochemical, cytochemical, and immunohistochemical techniques were applied to the pathological specimens.Results: Deficiencies of Zn, Cu, Mn, and vitamins A, C and E caused a loss of goblet cells in the conjunctiva and a prominent decrease of microvilli and microplicae in the conjunctiva and cornea. The elements in the goblet cells were changed in these conditions. In addition, epithelial cells showed poor fibrous development and abnormal distribution of chromatin in the nucleus.Zn, Cu, Mn, and vitamins A and E deficiencies caused photoreceptor cells to degenerate and disappear. Se deficiency reduced the horizontal and amacrine cells. Vitamin B(12) deficiency reduced nerve fibers in the nerve fiber layer of the retina. Mg deficiency induced multifocal necrosis in the retinal pigment epithelium and apoptotic nuclear changes in the photoreceptor cells. Cr deficiency showed abnormal phagocytosis of the photoreceptor outer segment discs in the retinal pigment epithelium. Vitamin B(12) was found to be related to the circadian rhythm in the retina.Deficiencies of Zn, Cu, Mn, and vitamins A, B(12), and E induced degeneration and disappearance of myelin lamellae in the myelinated optic nerve fibers.In hypervitaminosis A, lipid droplets appeared in the retinal pigment epithelium and alcohol dehydrogenase disappeared in the retinal pigment epithelium and photoreceptor outer segments. Excessive Al was toxic to the retina, which showed disappearance of photoreceptor cells. Al deposits were seen in dendrites and neurons in the outer plexiform layer.Zn seemed to be necessary for corneal epithelial cell wound healing.Discussion: Trace elements usually are contained in enzymes, which have many metabolic functions. They are related to synthesis and breakdown of many substances. Some trace elements such as Zn, Cu, Mn, and Se and vitamins including vitamins A, C, and E prevent peroxidation of lipids. Some vitamins have an affinity for specific tissues such as epithelial cells, nerve fibers, and neuronal cells and are needed for cell differentiation, development, and maintenance.Conclusion: Cu, Zn, Mn, Se, Mg, and Cr and vitamins A, B(12), C, and E are necessary for maintenance of cellular structure and metabolism.

Assessing posterior ocular structures in β-thalassemia minor.

PubMed

Arifoglu, Hasan Basri; Kucuk, Bekir; Duru, Necati; Altunel, Orhan; Gulhan, Ahmet; Ozen, Mustafa; Aygun, Bilal; Atas, Mustafa

2018-02-01

The aim of this study was to investigate the effect of β-thalassemia minor on choroidal, macular, and peripapillary retinal nerve fiber layer thickness. To form the sample, we recruited 40 patients with β-thalassemia minor and 44 healthy participants. We used spectral-domain optical coherence tomography to take all measurements of ocular thickness, as well as measured intraocular pressure, axial length, and central corneal thickness. We later analyzed correlations of hemoglobin levels with ocular parameters. A statistically significant difference emerged between patients with β-thalassemia minor and the healthy controls in terms of mean values of subfoveal, nasal, and temporal choroidal thickness (p = 0.001, p = 0.016, and p = 0.010, respectively). Except for central macular thickness, differences in paracentral macular thicknesses between the groups were also significant (superior: p < 0.001, inferior: p = 0.007, temporal: p = 0.001, and nasal: p = 0.005). Also, no statistically significant differences were noted for retinal nerve fiber layer thickness between two groups. Mean values of subfoveal, nasal, temporal choroidal, and macular thickness for the four quadrants were significantly lower in patients with β-thalassemia minor than in healthy controls.

Automated retinal nerve fiber layer defect detection using fundus imaging in glaucoma.

PubMed

Panda, Rashmi; Puhan, N B; Rao, Aparna; Padhy, Debananda; Panda, Ganapati

2018-06-01

Retinal nerve fiber layer defect (RNFLD) provides an early objective evidence of structural changes in glaucoma. RNFLD detection is currently carried out using imaging modalities like OCT and GDx which are expensive for routine practice. In this regard, we propose a novel automatic method for RNFLD detection and angular width quantification using cost effective redfree fundus images to be practically useful for computer-assisted glaucoma risk assessment. After blood vessel inpainting and CLAHE based contrast enhancement, the initial boundary pixels are identified by local minima analysis of the 1-D intensity profiles on concentric circles. The true boundary pixels are classified using random forest trained by newly proposed cumulative zero count local binary pattern (CZC-LBP) and directional differential energy (DDE) along with Shannon, Tsallis entropy and intensity features. Finally, the RNFLD angular width is obtained by random sample consensus (RANSAC) line fitting on the detected set of boundary pixels. The proposed method is found to achieve high RNFLD detection performance on a newly created dataset with sensitivity (SN) of 0.7821 at 0.2727 false positives per image (FPI) and the area under curve (AUC) value is obtained as 0.8733. Copyright © 2018 Elsevier Ltd. All rights reserved.

Functional and structural microanatomy of the fetal sciatic nerve.

PubMed

Creze, Maud; Zaitouna, Mazen; Krystel, Nyangoh Timoh; Diallo, Djibril; Lebacle, Cédric; Bellin, Marie-France; Ducreux, Denis; Benoit, Gérard; Bessede, Thomas

2017-10-01

The ultrastructure of a nerve has implications for surgical nerve repair. The aim of our study was to characterize the fascicular versus fibrillar anatomy and the autonomic versus somatic nature of the fetal sciatic nerve (SN). Immunohistochemistry for vesicular acetylcholine transporter, tyrosine hydroxylase, and peripheral myelin protein 22 was performed to identify cholinergic, adrenergic, and somatic axons, respectively, in the human fetal SN. Two-dimensional (2D) analysis and 3D reconstructions were performed. The fetal SN is composed of one-third stromal tissue and two-thirds neural tissue. Autonomic fibers are predominant over somatic fibers within the neural tissue. The distribution of somatic fibers is initially random, but then become topographically organized after intra- and interfascicular rearrangements have occurred within the nerve. The fetal model presents limitations but enables illustration of the nature of the nerve fibers and the 3D fascicular anatomy of the SN. Muscle Nerve 56: 787-796, 2017. © 2017 Wiley Periodicals, Inc.

Evaluation of Macular Ganglion Cell Complex and Peripapillary Retinal Nerve Fiber Layer in Primary Craniopharyngioma by Fourier-Domain Optical Coherence Tomography.

PubMed

Yang, Liu; Qu, Yuanzhen; Lu, Wen; Liu, Fengjun

2016-07-03

BACKGROUND The aim of this study was to compare the differences in macular ganglion cell complex (GCC) and peripapillary retinal nerve fiber layer (pRNFL) in child and adult patients with primary craniopharyngioma by Fourier-domain optical coherence tomography (FD-OCT) and to evaluate their significance in the diagnosis of primary craniopharyngioma. MATERIAL AND METHODS Ninety-six participants were divided into 3 groups: 32 in the child craniopharyngioma group (CCG) and 32 in the adult craniopharyngioma group (ACG) who were treated in Beijing Tiantan Hospital between November 2013 and October 2014, and 32 in the normal group (NG). All subjects were scanned by FD-OCT to map GCC and pRNFL thicknesses. Spearman correlation coefficient was used to assess the correlation between GCC and pRNFL thickness, and pRNFL thickness and optic nerve head (ONH) parameters, including horizontal cup-disc ratio (HCDR), vertical cup-disc ratio (VCDR), optic disc area (ODA), and cup area (CA), respectively. RESULTS The correlation between GCC and pRNFL thickness in the CCG was slightly stronger compared with the ACG. A significant difference in GCC thickness was observed among the CCG, ACG, and NG. Although the pRNFL thickness in both the CCG and ACG was significantly higher than that in NG, no significant difference in pRNFL thickness was detected between the 2 craniopharyngioma groups. The average, superior, and inferior pRNFL thicknesses were negatively correlated with VCDR in the CCG (in double eyes) and ACG (only in left eyes). CONCLUSIONS GCC was more sensitive than pRNFL in detecting optic nerve damage in the eyes of craniopharyngioma patients. A thinner pRNFL was especially correlated with VCDR in child craniopharyngioma patients.

Evaluation of Macular Ganglion Cell Complex and Peripapillary Retinal Nerve Fiber Layer in Primary Craniopharyngioma by Fourier-Domain Optical Coherence Tomography

PubMed Central

Yang, Liu; Qu, Yuanzhen; Lu, Wen; Liu, Fengjun

2016-01-01

Background The aim of this study was to compare the differences in macular ganglion cell complex (GCC) and peripapillary retinal nerve fiber layer (pRNFL) in child and adult patients with primary craniopharyngioma by Fourier-domain optical coherence tomography (FD-OCT) and to evaluate their significance in the diagnosis of primary craniopharyngioma. Material/Methods Ninety-six participants were divided into 3 groups: 32 in the child craniopharyngioma group (CCG) and 32 in the adult craniopharyngioma group (ACG) who were treated in Beijing Tiantan Hospital between November 2013 and October 2014, and 32 in the normal group (NG). All subjects were scanned by FD-OCT to map GCC and pRNFL thicknesses. Spearman correlation coefficient was used to assess the correlation between GCC and pRNFL thickness, and pRNFL thickness and optic nerve head (ONH) parameters, including horizontal cup-disc ratio (HCDR), vertical cup-disc ratio (VCDR), optic disc area (ODA), and cup area (CA), respectively. Results The correlation between GCC and pRNFL thickness in the CCG was slightly stronger compared with the ACG. A significant difference in GCC thickness was observed among the CCG, ACG, and NG. Although the pRNFL thickness in both the CCG and ACG was significantly higher than that in NG, no significant difference in pRNFL thickness was detected between the 2 craniopharyngioma groups. The average, superior, and inferior pRNFL thicknesses were negatively correlated with VCDR in the CCG (in double eyes) and ACG (only in left eyes). Conclusions GCC was more sensitive than pRNFL in detecting optic nerve damage in the eyes of craniopharyngioma patients. A thinner pRNFL was especially correlated with VCDR in child craniopharyngioma patients. PMID:27372909

Presence of Peripheral Neuropathy Is Associated With Progressive Thinning of Retinal Nerve Fiber Layer in Type 1 Diabetes.

PubMed

Dehghani, Cirous; Srinivasan, Sangeetha; Edwards, Katie; Pritchard, Nicola; Russell, Anthony W; Malik, Rayaz A; Efron, Nathan

2017-05-01

Reduced retinal nerve fiber layer (RNFL) thickness has been demonstrated in patients with diabetic peripheral neuropathy (DPN) in cross-sectional studies. This prospective study defines longitudinal alterations to the RNFL thickness in individuals with type 1 diabetes without (DPN-ve) and with (DPN+ve) DPN and in relation to risk factors for nerve damage. A cohort of 105 individuals with type 1 diabetes (20% DPN+ve) with predominantly mild or no retinopathy and no previous retinal photocoagulation underwent spectral-domain optical coherence tomography (SD-OCT) at baseline, 2 years, and 4 years. SD-OCT scans were acquired at 3.45-mm diameter around the optic nerve head and the overall RNFL and RNFL in the nasal, superior, temporal, and inferior quadrants were quantified. By including serial quantified RNFL parameters, linear mixed models were applied to assess the change in RNFL thickness over time and to explore the associations with other clinical variables. There was a significant decline in the overall RNFL thickness (-0.7 μm/y, P = 0.02) and RNFL in the superior quadrant (-1.9 μm/y, P < 0.01) in the DPN+ve group compared with DPN-ve group. The overall RNFL thickness and RNFL in the superior and nasal quadrants were inversely associated with age (β = -0.29, -0.41, and -0.29, respectively; P ≤ 0.02). Sex, retinopathy, diabetes duration, hemoglobin A1c, lipid profile, blood pressure, cigarette use, alcohol consumption, and body mass index did not show any significant effects (P > 0.05). Individuals with DPN showed a progressive RNFL thinning overall and in the superior quadrant, which was more pronounced in older individuals. There may be common pathways for retinal and peripheral neurodegeneration that are independent of conventional DPN risk factors.

The influence of corneal astigmatism on retinal nerve fiber layer thickness and optic nerve head parameter measurements by spectral-domain optical coherence tomography.

PubMed

Liu, Lin; Zou, Jun; Huang, Hui; Yang, Jian-guo; Chen, Shao-rong

2012-05-23

To evaluate the influence of corneal astigmatism (CA) on retinal nerve fiber layer (RNFL) thickness and optic nerve head(ONH) parameters measured with spectral-domain optical coherence tomography (OCT) in high myopes patients before refractive surgery. Seventy eyes of 35 consecutive refractive surgery candidates were included in this study. The mean age of the subjects was 26.42 ± 6.95 years, the average CA was -1.17 diopters (D; SD 0.64; range -0.2 to-3.3D), All subjects in this study were WTR CA. 34 eyes were in the normal CA group with a mean CA was -0.67 ± 0.28D, 36 eyes were in the high CA group with an average CA of -1.65 ± 0.49D. All subjects underwent ophthalmic examination and imaging with the Cirrus HD OCT. No significant difference was noted in the average cup-to-disk ratio, vertical cup-to-disk ratio and cup volume (all P values > 0.05). Compared with the normal CA group, the high CA group had a larger disc area and rim area, thinner RNFL thickness in the temporal quadrant, and the superotemporal and inferotemporal peaks were farther to the temporal horizon (All P values < 0.05). There were no significant differences between the two groups in global average RNFL thickness, as well as superior, nasal and inferior quadrant RNFL thickness (all P values > 0.05). The degree of with-the-rule CA should be considered when interpreting ONH parameters and peripapillary RNFL thickness measured by the Cirrus HD OCT. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1148475676881895.

Spectral Domain Optical Coherence Tomography in Glaucoma: Qualitative and Quantitative Analysis of the Optic Nerve Head and Retinal Nerve Fiber Layer (An AOS Thesis)

PubMed Central

Chen, Teresa C.

2009-01-01

Purpose: To demonstrate that video-rate spectral domain optical coherence tomography (SDOCT) can qualitatively and quantitatively evaluate optic nerve head (ONH) and retinal nerve fiber layer (RNFL) glaucomatous structural changes. To correlate quantitative SDOCT parameters with disc photography and visual fields. Methods: SDOCT images from 4 glaucoma eyes (4 patients) with varying stages of open-angle glaucoma (ie, early, moderate, late) were qualitatively contrasted with 2 age-matched normal eyes (2 patients). Of 61 other consecutive patients recruited in an institutional setting, 53 eyes (33 patients) met inclusion/exclusion criteria for quantitative studies. Images were obtained using two experimental SDOCT systems, one utilizing a superluminescent diode and the other a titanium:sapphire laser source, with axial resolutions of about 6 μm and 3 μm, respectively. Results: Classic glaucomatous ONH and RNFL structural changes were seen in SDOCT images. An SDOCT reference plane 139 μm above the retinal pigment epithelium yielded cup-disc ratios that best correlated with masked physician disc photography cup-disc ratio assessments. The minimum distance band, a novel SDOCT neuroretinal rim parameter, showed good correlation with physician cup-disc ratio assessments, visual field mean deviation, and pattern standard deviation (P values range, .0003–.024). RNFL and retinal thickness maps correlated well with disc photography and visual field testing. Conclusions: To our knowledge, this thesis presents the first comprehensive qualitative and quantitative evaluation of SDOCT images of the ONH and RNFL in glaucoma. This pilot study provides basis for developing more automated quantitative SDOCT-specific glaucoma algorithms needed for future prospective multicenter national trials. PMID:20126502

Central projections of the lateral line and eighth nerves in the bowfin, Amia calva.

PubMed

McCormick, C A

1981-03-20

The first-order connections of the anterior and posterior lateral line nerves and of the eighth nerve were determined in the bowfin, Amia calva, using experimental degeneration and anterograde HRP transport techniques. The termination sites of these nerves define a dorsal lateralis cell column and a ventral octavus cell column. The anterior and posterior lateralis nerves distribute ipsilaterally to two medullary nuclei-nucleus medialis and nucleus caudalis. Nucleus medialis comprises the rostral two-thirds of the lateralis column and contains large, Purkinje-like cells dorsally and polygonal, granule, and fusiform cells ventrally. Nucleus caudalis is located posterior to nucleus medialis and consists of small, granule cells. Anterior lateralis fibers terminate ventrally to ventromedially in both nucleus medialis and nucleus caudalis. Posterior lateralis fibers terminate dorsally to dorsolaterally within these two nuclei. A sparse anterior lateralis input may also be present on the dendrites of one of the nuclei within the octavus cell column, nucleus magnocellularis. In contrast, the anterior and posterior rami of the eighth nerve each terminate within four medullary nuclei which comprise the octavus cell column: the anterior, magnocellular, descending, and posterior octavus nuclei. An eighth nerve projection to the medial reticular formation is also present. Some fibers of the lateralis and eighth nerves terminate within the ipsilateral eminentia granularis of the cerebellum. Lateralis fibers distribute to approximately the lateral half of this structure with posterior lateral line fibers terminating laterally and anterior lateral line fibers terminating medially. Eighth nerve fibers distribute to the medial half of the eminentia granularis.

[Myelinated nerve fibers coexisted with epiretinal membrane in macula--case report].

PubMed

Swiech-Zubilewicz, Anna; Bieliński, Paweł; Dolar-Szczasny, Joanna; Zarnowski, Tomasz

2012-01-01

We describe a case of peripapillary myelinated retinal nerve fibers complicated by epiretinal membrane in region of macula. 72 years old man was refered to our Clinic with suspicion of retinal detachment of right eye. Visual acuity of right eye was based to 0.05, in left eye was 0.5. IOP was normal in both eyes. In biomcroscopic evaluation the slight cortical cataract was observed in both eyes. Stereoscopic evaluation of right eye revealed the presence of massive peripapillary myelinated retinal nerve fibers and epiretinal membrane in the macula. In the left eye the less intense peripapillary myelinated retinal nerve fibers were noticed as well and the macular region was unchanged. With the use of OCT examination of the retina the presence of epiretinal membrane in the right eye was confirmed. OCT in the fellow eye presented an undisturbed foveal profile without any epiretinal abnormalities. Myelinated retinal nerve fibers can be complicated by epiretinal membrane. Probably the presence of macular pathologies depends on the extensions of nerve fibers. OCT examination is very helpful to give a proper diagnosis.

Vision and the dimensions of nerve fibers.

PubMed

Wade, Nicholas J

2005-12-01

Vision provided the obvious source of determining the dimensions of nerve fibers when suitable achromatic microscopes were directed at neural tissue in the 1830s. The earlier microscopes of Hooke and Leeuwenhoek were unable to resolve such small structures adequately. However, it was not Hooke's microscope that led to an estimate of the dimensions of nerve fibers, but his experiments on the limits of visual resolution; he determined that a separation of one minute of arc was the minimum that could normally be seen. Descartes had earlier speculated that the retina consisted of the ends of fibers of the optic nerve, and that their size defined the limits of what could be seen. Estimates of the diameters of nerve fibers were made on the basis of human visual acuity by Porterfield in 1738; he calculated the diameters of nerve fibers in the retina as one 7,200th part of an inch (0.0035 mm), based on the resolution of one minute as the minimum visible. In the same year, Jurin questioned the reliability of such estimates because of variations in visual resolution with different stimuli.

Determination of Nerve Fiber Diameter Distribution From Compound Action Potential: A Continuous Approach.

PubMed

Un, M Kerem; Kaghazchi, Hamed

2018-01-01

When a signal is initiated in the nerve, it is transmitted along each nerve fiber via an action potential (called single fiber action potential (SFAP)) which travels with a velocity that is related with the diameter of the fiber. The additive superposition of SFAPs constitutes the compound action potential (CAP) of the nerve. The fiber diameter distribution (FDD) in the nerve can be computed from the CAP data by solving an inverse problem. This is usually achieved by dividing the fibers into a finite number of diameter groups and solve a corresponding linear system to optimize FDD. However, number of fibers in a nerve can be measured sometimes in thousands and it is possible to assume a continuous distribution for the fiber diameters which leads to a gradient optimization problem. In this paper, we have evaluated this continuous approach to the solution of the inverse problem. We have utilized an analytical function for SFAP and an assumed a polynomial form for FDD. The inverse problem involves the optimization of polynomial coefficients to obtain the best estimate for the FDD. We have observed that an eighth order polynomial for FDD can capture both unimodal and bimodal fiber distributions present in vivo, even in case of noisy CAP data. The assumed FDD distribution regularizes the ill-conditioned inverse problem and produces good results.

Modelling the impact of altered axonal morphometry on the response of regenerative nervous tissue to electrical stimulation through macro-sieve electrodes.

PubMed

Zellmer, Erik R; MacEwan, Matthew R; Moran, Daniel W

2018-04-01

Regenerated peripheral nervous tissue possesses different morphometric properties compared to undisrupted nerve. It is poorly understood how these morphometric differences alter the response of the regenerated nerve to electrical stimulation. In this work, we use computational modeling to explore the electrophysiological response of regenerated and undisrupted nerve axons to electrical stimulation delivered by macro-sieve electrodes (MSEs). A 3D finite element model of a peripheral nerve segment populated with mammalian myelinated axons and implanted with a macro-sieve electrode has been developed. Fiber diameters and morphometric characteristics representative of undisrupted or regenerated peripheral nervous tissue were assigned to core conductor models to simulate the two tissue types. Simulations were carried out to quantify differences in thresholds and chronaxie between undisrupted and regenerated fiber populations. The model was also used to determine the influence of axonal caliber on recruitment thresholds for the two tissue types. Model accuracy was assessed through comparisons with in vivo recruitment data from chronically implanted MSEs. Recruitment thresholds of individual regenerated fibers with diameters  >2 µm were found to be lower compared to same caliber undisrupted fibers at electrode to fiber distances of less than about 90-140 µm but roughly equal or higher for larger distances. Caliber redistributions observed in regenerated nerve resulted in an overall increase in average recruitment thresholds and chronaxie during whole nerve stimulation. Modeling results also suggest that large diameter undisrupted fibers located close to a longitudinally restricted current source such as the MSE have higher average recruitment thresholds compared to small diameter fibers. In contrast, large diameter regenerated nerve fibers located in close proximity of MSE sites have, on average, lower recruitment thresholds compared to small fibers. Utilizing regenerated fiber morphometry and caliber distributions resulted in accurate predictions of in vivo recruitment data. Our work uses computational modeling to show how morphometric differences between regenerated and undisrupted tissue results in recruitment threshold discrepancies, quantifies these differences, and illustrates how large undisrupted nerve fibers close to longitudinally restricted current sources have higher recruitment thresholds compared to adjacently positioned smaller fibers while the opposite is true for large regenerated fibers.

Modelling the impact of altered axonal morphometry on the response of regenerative nervous tissue to electrical stimulation through macro-sieve electrodes

NASA Astrophysics Data System (ADS)

Zellmer, Erik R.; MacEwan, Matthew R.; Moran, Daniel W.

2018-04-01

Objective. Regenerated peripheral nervous tissue possesses different morphometric properties compared to undisrupted nerve. It is poorly understood how these morphometric differences alter the response of the regenerated nerve to electrical stimulation. In this work, we use computational modeling to explore the electrophysiological response of regenerated and undisrupted nerve axons to electrical stimulation delivered by macro-sieve electrodes (MSEs). Approach. A 3D finite element model of a peripheral nerve segment populated with mammalian myelinated axons and implanted with a macro-sieve electrode has been developed. Fiber diameters and morphometric characteristics representative of undisrupted or regenerated peripheral nervous tissue were assigned to core conductor models to simulate the two tissue types. Simulations were carried out to quantify differences in thresholds and chronaxie between undisrupted and regenerated fiber populations. The model was also used to determine the influence of axonal caliber on recruitment thresholds for the two tissue types. Model accuracy was assessed through comparisons with in vivo recruitment data from chronically implanted MSEs. Main results. Recruitment thresholds of individual regenerated fibers with diameters  >2 µm were found to be lower compared to same caliber undisrupted fibers at electrode to fiber distances of less than about 90-140 µm but roughly equal or higher for larger distances. Caliber redistributions observed in regenerated nerve resulted in an overall increase in average recruitment thresholds and chronaxie during whole nerve stimulation. Modeling results also suggest that large diameter undisrupted fibers located close to a longitudinally restricted current source such as the MSE have higher average recruitment thresholds compared to small diameter fibers. In contrast, large diameter regenerated nerve fibers located in close proximity of MSE sites have, on average, lower recruitment thresholds compared to small fibers. Utilizing regenerated fiber morphometry and caliber distributions resulted in accurate predictions of in vivo recruitment data. Significance. Our work uses computational modeling to show how morphometric differences between regenerated and undisrupted tissue results in recruitment threshold discrepancies, quantifies these differences, and illustrates how large undisrupted nerve fibers close to longitudinally restricted current sources have higher recruitment thresholds compared to adjacently positioned smaller fibers while the opposite is true for large regenerated fibers.

Association between retinal nerve fiber layer thickness and magnetic resonance imaging findings and intelligence in patients with multiple sclerosis.

PubMed

Ashtari, Fereshteh; Emami, Parisa; Akbari, Mojtaba

2015-01-01

Multiple Sclerosis (MS) is a neurological disease in which demyelination and axonal loss leads to progressive disability. Cognition impairment is among the most common complication. Studying axonal loss in the retina is a new marker for MS. The main goal of our study is to search for correlations between magnetic resonance imaging (MRI) findings and the retinal nerve fiber layer (RNFL) thickness at the macula and head of the optic nerve and Wechsler Adult Intelligence Scale-Revised (WAIS-R) Scores that assess multiple domains of intelligence, and to explore the relationship between changes in the RNFL thickness with intellectual and cognitive dysfunction. A prospective cross-sectional study was conducted at the University Hospital of Kashani, Isfahan, Iran, from September to December 2013. All patients were assessed with a full-scale intelligence quotient (IQ) on the WAIS-R. An optical coherence tomography study and brain MRI were performed in the same week for all the patients. Statistical analysis was conducted by using a bivariate correlation, by utilizing SPSS 20.0. A P value ≤ 0.05 was the threshold of statistical significance. Examination of a 100 patients showed a significant correlation between the average RNFL thickness of the macula and the verbal IQ (P value = 0.01) and full IQ (P value = 0.01). There was a significant correlation between brain atrophy and verbal IQ. The RNFL loss was correlated with verbal IQ and full IQ.

Peptide therapy with pentadecapeptide BPC 157 in traumatic nerve injury.

PubMed

Gjurasin, Miroslav; Miklic, Pavle; Zupancic, Bozidar; Perovic, Darko; Zarkovic, Kamelija; Brcic, Luka; Kolenc, Danijela; Radic, Bozo; Seiwerth, Sven; Sikiric, Predrag

2010-02-25

We focused on the healing of rat transected sciatic nerve and improvement made by stable gastric pentadecapeptide BPC 157 (10 microg, 10ng/kg) applied shortly after injury (i) intraperitoneally/intragastrically/locally, at the site of anastomosis, or after (ii) non-anastomozed nerve tubing (7 mm nerve segment resected) directly into the tube. Improvement was shown clinically (autotomy), microscopically/morphometrically and functionally (EMG, one or two months post-injury, walking recovery (sciatic functional index (SFI)) at weekly intervals). BPC 157-rats exhibited faster axonal regeneration: histomorphometrically (improved presentation of neural fascicles, homogeneous regeneration pattern, increased density and size of regenerative fibers, existence of epineural and perineural regeneration, uniform target orientation of regenerative fibers, and higher proportion of neural vs. connective tissue, all fascicles in each nerve showed increased diameter of myelinated fibers, thickness of myelin sheet, number of myelinated fibers per area and myelinated fibers as a percentage of the nerve transected area and the increased blood vessels presentation), electrophysiologically (increased motor action potentials), functionally (improved SFI), the autotomy absent. Thus, BPC 157 markedly improved rat sciatic nerve healing. Copyright 2009 Elsevier B.V. All rights reserved.

Small fiber neuropathy in women with fibromyalgia. An in vivo assessment using corneal confocal bio-microscopy.

PubMed

Ramírez, Manuel; Martínez-Martínez, Laura-Aline; Hernández-Quintela, Everardo; Velazco-Casapía, Jorge; Vargas, Angélica; Martínez-Lavín, Manuel

2015-10-01

A consistent line of investigation suggests that fibromyalgia is a neuropathic pain syndrome. This outlook has been recently reinforced by several controlled studies that describe decreased small nerve fiber density in skin biopsies of patients with fibromyalgia. The cornea receives the densest small fiber innervation of the body. Corneal confocal bio-microscopy is a new noninvasive method to evaluate small nerve fiber morphology. Our objective was to assess corneal small nerve fiber morphology in patients with fibromyalgia, and to associate corneal nerve microscopic features with neuropathic pain descriptors and other fibromyalgia symptoms. We studied 17 female patients with fibromyalgia and 17 age-matched healthy control subjects. All the participants completed different questionnaires regarding the symptoms of fibromyalgia, including a neuropathic pain survey. A central corneal thickness scan was obtained with a confocal microscope. Nerve measurements were made by a single ophthalmologist without knowledge of the clinical diagnosis. Stromal nerve thickness was defined as the mean value between the widest and the narrowest portion of each analyzed stromal nerve. Corneal sub-basal plexus nerve density was also assessed. Patients with fibromyalgia had stromal nerve thickness of 5.0 ± 1.0 µm (mean ± standard deviation) significantly different from that of control's values (6.1 ± 1.3) p = 0.01. Patients also had decreased sub-basal plexus nerve density per square millimeter (85 ± 29) vs. 107 ± 26 of controls p = 0.02. When controls and patients were grouped together, there was an association between stromal nerve slenderness and neuropathic pain descriptors (Fisher's exact test p = 0.007). Women suffering from fibromyalgia have thinner corneal stromal nerves and diminished sub-basal plexus nerve density when compared to healthy controls. Nerve scarcity is associated with neuropathic pain descriptors. Small fiber neuropathy may play a role in the pathogenesis of fibromyalgia pain. Corneal confocal microscopy could become a useful test in the study of patients with fibromyalgia. Copyright © 2015. Published by Elsevier Inc.

Peripapillary Retinoschisis in Glaucomatous Eyes

PubMed Central

Lee, Eun Ji; Kim, Tae-Woo; Kim, Mijin; Choi, Yun Jeong

2014-01-01

Purpose To investigate the structural and clinical characteristics of peripapillary retinoschisis observed in glaucomatous eyes using spectral-domain optical coherence tomography (SD-OCT). Methods Circumpapillary retinal nerve fiber layer (cpRNFL) and macular cross-hair SD-OCT scans and infrared fundus images of the glaucoma patients from the Investigating Glaucoma Progression Study (IGPS) and healthy volunteers were reviewed. Optic disc images obtained using enhanced depth imaging (EDI) SD-OCT were also evaluated. The structural characteristics and clinical course of the retinoschisis associated with glaucoma were investigated. Results Twenty-five retinoschisis areas were found in 22 of the 372 patients (5.9%) included in the IGPS, and in 1 area in 1 of 187 healthy control subjects (0.5%). In the 22 glaucomatous eyes with retinoschisis, the schisis was attached to the optic disc and overlapped with the retinal nerve fiber layer (RNFL) defect. The RNFL was the layer most commonly affected by the retinoschisis, either alone or together with other deeper layers. Acquired optic disc pit was identified in 8 eyes on disc photography and/or B-scan images obtained by EDI SD-OCT. Spontaneous resolution of this condition was observed in nine eyes. No retinal detachment or macular involvement of the retinoschisis was observed in any of the eyes. Multivariate analysis showed a significant influence of a higher intraocular pressure at SD-OCT scanning on the presence of retinoschisis (Odds ratio  = 1.418, P = 0.001). Conclusions The present study investigated 22 cases of peripapillary retinoschisis in glaucomatous eyes. The retinoschisis was attached to the optic nerve and topographically correlated with RNFL defect. It often resolved spontaneously without causing severe visual disturbance. Care should be taken not to overestimate the RNFL thickness in eyes with retinoschisis, and also not to misinterpret the resolution of retinoschisis as a rapid glaucomatous RNFL deterioration. PMID:24587238

Retinal optical coherence tomography at 1 μm with dynamic focus control and axial motion tracking

NASA Astrophysics Data System (ADS)

Cua, Michelle; Lee, Sujin; Miao, Dongkai; Ju, Myeong Jin; Mackenzie, Paul J.; Jian, Yifan; Sarunic, Marinko V.

2016-02-01

High-resolution optical coherence tomography (OCT) retinal imaging is important to noninvasively visualize the various retinal structures to aid in better understanding of the pathogenesis of vision-robbing diseases. However, conventional OCT systems have a trade-off between lateral resolution and depth-of-focus. In this report, we present the development of a focus-stacking OCT system with automatic focus optimization for high-resolution, extended-focal-range clinical retinal imaging by incorporating a variable-focus liquid lens into the sample arm optics. Retinal layer tracking and selection was performed using a graphics processing unit accelerated processing platform for focus optimization, providing real-time layer-specific en face visualization. After optimization, multiple volumes focused at different depths were acquired, registered, and stitched together to yield a single, high-resolution focus-stacked dataset. Using this system, we show high-resolution images of the retina and optic nerve head, from which we extracted clinically relevant parameters such as the nerve fiber layer thickness and lamina cribrosa microarchitecture.

Retinal optical coherence tomography at 1 μm with dynamic focus control and axial motion tracking.

PubMed

Cua, Michelle; Lee, Sujin; Miao, Dongkai; Ju, Myeong Jin; Mackenzie, Paul J; Jian, Yifan; Sarunic, Marinko V

2016-02-01

High-resolution optical coherence tomography (OCT) retinal imaging is important to noninvasively visualize the various retinal structures to aid in better understanding of the pathogenesis of vision-robbing diseases. However, conventional OCT systems have a trade-off between lateral resolution and depth-of-focus. In this report, we present the development of a focus-stacking OCT system with automatic focus optimization for high-resolution, extended-focal-range clinical retinal imaging by incorporating a variable-focus liquid lens into the sample arm optics. Retinal layer tracking and selection was performed using a graphics processing unit accelerated processing platform for focus optimization, providing real-time layer-specific en face visualization. After optimization, multiple volumes focused at different depths were acquired, registered, and stitched together to yield a single, high-resolution focus-stacked dataset. Using this system, we show high-resolution images of the retina and optic nerve head, from which we extracted clinically relevant parameters such as the nerve fiber layer thickness and lamina cribrosa microarchitecture.

Early Corneal Cellular and Nerve Fiber Pathology in Young Patients With Type 1 Diabetes Mellitus Identified Using Corneal Confocal Microscopy.

PubMed

Szalai, Eszter; Deák, Eszter; Módis, László; Németh, Gábor; Berta, András; Nagy, Annamária; Felszeghy, Eniko; Káposzta, Rita; Malik, Rayaz A; Csutak, Adrienne

2016-03-01

The aim of this study was to quantify epithelial, stromal, and endothelial cell density, and subbasal nerve morphology in young patients with type 1 diabetes mellitus with and without diabetic retinopathy. A total of 28 young patients (mean age, 22.86 ± 9.05 years) with type 1 diabetes, with (n = 18) and without (n = 10) retinopathy, and 17 age-matched healthy control subjects (mean age, 26.53 ± 2.43 years) underwent corneal confocal microscopy (CCM). We found significantly lower epithelial (P < 0.0001) and endothelial (P = 0.001) cell densities and higher keratocyte cell density (P = 0.024) in patients with type 1 diabetes compared to controls. Significantly lower corneal nerve fiber density (P = 0.004), nerve branch density (P = 0.004), total nerve branch density (P = 0.04), and nerve fiber length (P = 0.001), and greater nerve fiber width (P = 0.04) were observed in patients with type 1 diabetes compared to control subjects. Significantly lower epithelial (P < 0.001) and endothelial (P = 0.02) cell densities, nerve branch density (P = 0.02), and nerve fiber length (P = 0.04), and significantly higher keratocyte cell density (P = 0.02) were found in patients with type 1 diabetes without retinopathy compared to control subjects. Corneal confocal microscopy identifies corneal cellular and small nerve fiber pathology in young patients with type 1 diabetes without retinopathy, which increases in severity in those with retinopathy. Corneal confocal microscopy appears to have considerable use as an imaging biomarker for early subclinical pathology in young patients with type 1 diabetes mellitus.

Ratiometric analysis of in vivo retinal layer thicknesses in multiple sclerosis

NASA Astrophysics Data System (ADS)

Bhaduri, Basanta; Nolan, Ryan M.; Shelton, Ryan L.; Pilutti, Lara A.; Motl, Robert W.; Boppart, Stephen A.

2016-09-01

We performed ratiometric analysis of retinal optical coherence tomography images for the first time in multiple sclerosis (MS) patients. The ratiometric analysis identified differences in several retinal layer thickness ratios in the cohort of MS subjects without a history of optic neuritis (ON) compared to healthy control (HC) subjects, and there was no difference in standard retinal nerve fiber layer thickness (RNFLT). The difference in such ratios between HC subjects and those with mild MS-disability, without a difference in RNFLT, further suggests the possibility of using layer ratiometric analysis for detecting early retinal changes in MS. Ratiometric analysis may be useful and potentially more sensitive for detecting disease changes in MS.

PATHOGENESIS OF OPTIC DISC EDEMA IN RAISED INTRACRANIAL PRESSURE

PubMed Central

Hayreh, Sohan Singh

2015-01-01

Optic disc edema in raised intracranial pressure was first described in 1853. Ever since, there has been a plethora of controversial hypotheses to explain its pathogenesis. I have explored the subject comprehensively by doing basic, experimental and clinical studies. My objective was to investigate the fundamentals of the subject, to test the validity of the previous theories, and finally, based on all these studies, to find a logical explanation for the pathogenesis. My studies included the following issues pertinent to the pathogenesis of optic disc edema in raised intracranial pressure: the anatomy and blood supply of the optic nerve, the roles of the sheath of the optic nerve, of the centripetal flow of fluids along the optic nerve, of compression of the central retinal vein, and of acute intracranial hypertension and its associated effects. I found that, contrary to some previous claims, an acute rise of intracranial pressure was not quickly followed by production of optic disc edema. Then, in rhesus monkeys, I produced experimentally chronic intracranial hypertension by slowly increasing in size space-occupying lesions, in different parts of the brain. Those produced raised cerebrospinal fluid pressure (CSFP) and optic disc edema, identical to those seen in patients with elevated CSFP. Having achieved that, I investigated various aspects of optic disc edema by ophthalmoscopy, stereoscopic color fundus photography and fluorescein fundus angiography, and light microscopic, electron microscopic, horseradish peroxidase and axoplasmic transport studies, and evaluated the effect of opening the sheath of the optic nerve on the optic disc edema. This latter study showed that opening the sheath resulted in resolution of optic disc edema on the side of the sheath fenestration, in spite of high intracranial CSFP, proving that a rise of CSFP in the sheath was the essential pre-requisite for the development of optic disc edema. I also investigated optic disc edema with raised CSFP in patients, by evaluating optic disc and fundus changes by stereoscopic fundus photography and fluorescein fundus angiography. Based on the combined information from all the studies discussed above, it is clear that the pathogenesis of optic disc edema in raised intracranial pressure is a mechanical phenomenon. It is primarily due to a rise of CSFP in the optic nerve sheath, which produces axoplasmic flow stasis in the optic nerve fibers in the surface nerve fiber layer and prelaminar region of the optic nerve head. Axoplasmic flow stasis then results in swelling of the nerve fibers, and consequently of the optic disc. Swelling of the nerve fibers and of the optic disc secondarily compresses the fine, low-pressure venules in that region, resulting in venous stasis and fluid leakage; that leads to the accumulation of extracellular fluid. Contrary to the previous theories, the various vascular changes seen in optic disc edema are secondary and not primary. Thus, optic disc edema in raised CSFP is due to a combination of swollen nerve fibers and the accumulation of extracellular fluid. My studies also provided information about the pathogeneses of visual disturbances in raised intracranial pressure. PMID:26453995

Pathogenesis of optic disc edema in raised intracranial pressure.

PubMed

Hayreh, Sohan Singh

2016-01-01

Optic disc edema in raised intracranial pressure was first described in 1853. Ever since, there has been a plethora of controversial hypotheses to explain its pathogenesis. I have explored the subject comprehensively by doing basic, experimental and clinical studies. My objective was to investigate the fundamentals of the subject, to test the validity of the previous theories, and finally, based on all these studies, to find a logical explanation for the pathogenesis. My studies included the following issues pertinent to the pathogenesis of optic disc edema in raised intracranial pressure: the anatomy and blood supply of the optic nerve, the roles of the sheath of the optic nerve, of the centripetal flow of fluids along the optic nerve, of compression of the central retinal vein, and of acute intracranial hypertension and its associated effects. I found that, contrary to some previous claims, an acute rise of intracranial pressure was not quickly followed by production of optic disc edema. Then, in rhesus monkeys, I produced experimentally chronic intracranial hypertension by slowly increasing in size space-occupying lesions, in different parts of the brain. Those produced raised cerebrospinal fluid pressure (CSFP) and optic disc edema, identical to those seen in patients with elevated CSFP. Having achieved that, I investigated various aspects of optic disc edema by ophthalmoscopy, stereoscopic color fundus photography and fluorescein fundus angiography, and light microscopic, electron microscopic, horseradish peroxidase and axoplasmic transport studies, and evaluated the effect of opening the sheath of the optic nerve on the optic disc edema. This latter study showed that opening the sheath resulted in resolution of optic disc edema on the side of the sheath fenestration, in spite of high intracranial CSFP, proving that a rise of CSFP in the sheath was the essential pre-requisite for the development of optic disc edema. I also investigated optic disc edema with raised CSFP in patients, by evaluating optic disc and fundus changes by stereoscopic fundus photography and fluorescein fundus angiography. Based on the combined information from all the studies discussed above, it is clear that the pathogenesis of optic disc edema in raised intracranial pressure is a mechanical phenomenon. It is primarily due to a rise of CSFP in the optic nerve sheath, which produces axoplasmic flow stasis in the optic nerve fibers in the surface nerve fiber layer and prelaminar region of the optic nerve head. Axoplasmic flow stasis then results in swelling of the nerve fibers, and consequently of the optic disc. Swelling of the nerve fibers and of the optic disc secondarily compresses the fine, low-pressure venules in that region, resulting in venous stasis and fluid leakage; that leads to the accumulation of extracellular fluid. Contrary to the previous theories, the various vascular changes seen in optic disc edema are secondary and not primary. Thus, optic disc edema in raised CSFP is due to a combination of swollen nerve fibers and the accumulation of extracellular fluid. My studies also provided information about the pathogeneses of visual disturbances in raised intracranial pressure. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Overwhelming Majority but not All Motor Fibers of the Bifid Recurrent Laryngeal Nerve are Located in the Anterior Extralaryngeal Branch.

PubMed

Barczyński, Marcin; Stopa, Małgorzata; Konturek, Aleksander; Nowak, Wojciech

2016-03-01

Few small studies reported that motor fibers are located exclusively in the anterior branch of the bifid recurrent laryngeal nerve (RLN). The aim of this study was to investigate the location of the motor fibers to the intrinsic muscles of the larynx among the bifid RLNs, and assess the prevalence of RLN injury with respect to nerve branching in a pragmatic trial. This was a prospective cohort study of 1250 patients who underwent total thyroidectomy with intraoperative neural monitoring. The primary outcome was the position of the motor fibers in the bifid nerves. Adduction of the vocal folds was detected by the endotracheal tube electromyography and abduction by finger palpation of muscle contraction in the posterior cricoarytenoid. The secondary outcomes were the prevalence of the RLN branching and the prevalence of RLN injury in bifid versus non-bifid nerves. The bifid RLNs were identified in 613/2500 (24.5%) nerves at risk, including 92 (7.4%) patients with bilateral bifurcations. The motor fibers were present exclusively in the anterior branch in 605/613 (98.7%) bifid nerves, and in both the RLN branches in 8/613 (1.3%) bifid nerves. Prevalence of RLN injury was 5.2 versus 1.6% for the bifid versus non-bifid nerves (p < 0.001), odds ratio 2.98 (95% confidence interval 1.79-4.95; p < 0.001). The motor fibers of the RLN are located in the anterior extralaryngeal branch in the vast majority of but not in all patients. In rare cases, the motor fibers for adduction or abduction are located in the posterior branch of the RLN. As the bifid nerves are more prone to injury than non-branched nerves, meticulous dissection is recommended to assure preservation of all the branches of the RLN during thyroidectomy.

Sustained reduction in blood pressure from electrical activation of the baroreflex is mediated via the central pathway of unmyelinated baroreceptors.

PubMed

Turner, Michael J; Kawada, Toru; Shimizu, Shuji; Sugimachi, Masaru

2014-06-13

This study aims to identify the contribution of myelinated (A-fiber) and unmyelinated (C-fiber) baroreceptor central pathways to the baroreflex control of sympathetic nerve activity and arterial pressure. Two binary white noise stimulation protocols were used to electrically stimulate the aortic depressor nerve and activate reflex responses from either A-fiber (3 V, 20-100 Hz) or C-fiber (20 V, 0-10 Hz) baroreceptor in anesthetized Sprague-Dawley rats (n=10). Transfer function analysis was performed between stimulation and sympathetic nerve activity (central arc), sympathetic nerve activity and arterial pressure (peripheral arc), and stimulation and arterial pressure (Stim-AP arc). The central arc transfer function from nerve stimulation to splanchnic sympathetic nerve activity displayed derivative characteristics for both stimulation protocols. However, the modeled steady-state gain (0.28 ± 0.04 vs. 4.01 ± 0.2%·Hz(-1), P<0.001) and coherence at 0.01 Hz (0.44 ± 0.05 vs. 0.81 ± 0.03, P<0.05) were significantly lower for A-fiber stimulation compared with C-fiber stimulation. The slope of the dynamic gain was higher for A-fiber stimulation (14.82 ± 1.02 vs. 7.21 ± 0.79 dB·decade(-1), P<0.001). The steady-state gain of the Stim-AP arc was also significantly lower for A-fiber stimulation compared with C-fiber stimulation (0.23 ± 0.05 vs. 3.05 ± 0.31 mmHg·Hz(-1), P<0.001). These data indicate that the A-fiber central pathway contributes to high frequency arterial pressure regulation and the C-fiber central pathway provides more sustained changes in sympathetic nerve activity and arterial pressure. A sustained reduction in arterial pressure from electrical stimulation of arterial baroreceptor afferents is likely mediated through the C-fiber central pathway. Copyright © 2014 Elsevier Inc. All rights reserved.

Cutaneous somatic and autonomic nerve TDP-43 deposition in amyotrophic lateral sclerosis.

PubMed

Ren, Yuting; Liu, Wenxiu; Li, Yifan; Sun, Bo; Li, Yanran; Yang, Fei; Wang, Hongfen; Li, Mao; Cui, Fang; Huang, Xusheng

2018-05-26

To evaluate the involvement of the sensory and autonomic nervous system in amyotrophic lateral sclerosis (ALS) and to determine whether TDP-43/pTDP-43 deposits in skin nerve fibers signify a valuable biomarker for ALS. Eighteen patients with ALS and 18 age- and sex-matched control subjects underwent physical examinations, in addition to donating skin biopsies from the distal leg. The density of epidermal, Meissner's corpuscle (MC), sudomotor, and pilomotor nerve fibers were measured. Confocal microscopy was used to determine the cutaneous somatic and autonomic nerve fiber density and TDP-43/pTDP-43 deposition. Intraepidermal nerve fiber density (IENFD) was reduced in individuals with ALS (P < 0.001). MC density (MCD) (P = 0.001), sweat gland nerve fiber density (SGNFD) (P < 0.001), and pilomotor nerve fiber density (PNFD) (P < 0.001) were all reduced in ALS patients. The SGNFD correlated with the small-fiber neuropathy Symptoms Inventory Questionnaire (SFN-SIQ), VAS and age. The SFN-SIQ was higher in ALS with sensory symptoms than without sensory symptoms (P = 0.000). Furthermore, the SFN-SIQ was higher in ALS with autonomic symptoms than without autonomic symptoms (P = 0.002). SFN-SIQ was higher in ALS patients that were pTDP-43 positive than pTDP-43 negative (P = 0.04), respectively. We established in the peripheral nervous system that higher SFN-SIQ and VAS was involved in ALS, indicating the loss of SGNF. The deposition of TDP-43/pTDP-43 in ALS nerve fibers may indicate an important role in the underlying pathogenesis of ALS. This observation might be used as a potential biomarker for diagnosing ALS.

BREAST CANCER-INDUCED BONE REMODELING, SKELETAL PAIN AND SPROUTING OF SENSORY NERVE FIBERS

PubMed Central

Bloom, Aaron P.; Jimenez-Andrade, Juan M.; Taylor, Reid N.; Castañeda-Corral, Gabriela; Kaczmarska, Magdalena J.; Freeman, Katie T.; Coughlin, Kathleen A.; Ghilardi, Joseph R.; Kuskowski, Michael A.; Mantyh, Patrick W.

2011-01-01

Breast cancer metastasis to bone is frequently accompanied by pain. What remains unclear is why this pain tends to become more severe and difficult to control with disease progression. Here we test the hypothesis that with disease progression sensory nerve fibers that innervate the breast cancer bearing bone undergo a pathological sprouting and reorganization, which in other non-malignant pathologies has been shown to generate and maintain chronic pain. Injection of human breast cancer cells (MDA-MB-231-BO) into the femoral intramedullary space of female athymic nude mice induces sprouting of calcitonin gene-related peptide (CGRP+) sensory nerve fibers. Nearly all CGRP+ nerve fibers that undergo sprouting also co-express tropomyosin receptor kinase A (TrkA+) and growth associated protein-43 (GAP43+). This ectopic sprouting occurs in periosteal sensory nerve fibers that are in close proximity to breast cancer cells, tumor-associated stromal cells and remodeled cortical bone. Therapeutic treatment with an antibody that sequesters nerve growth factor (NGF), administered when the pain and bone remodeling were first observed, blocks this ectopic sprouting and attenuates cancer pain. The present data suggest that the breast cancer cells and tumor-associated stromal cells express and release NGF, which drives bone pain and the pathological reorganization of nearby CGRP+ / TrkA+ / GAP43+ sensory nerve fibers. PMID:21497141

Evaluation of Central Macular Thickness and Retinal Nerve Fiber Layer Thickness using Spectral Domain Optical Coherence Tomography in a Tertiary Care Hospital

PubMed Central

Saini, VK; Gupta, Saroj; Sharma, Anjali

2014-01-01

ABSTRACT Purpose: To evaluate the normative data of macular thickness and retinal nerve fiber layer thickness (RNFL) among normal subjects using spectral domain optical coherence tomography (OCT). Materials and methods: Normal subjects presenting to a tertiary medical hospital were included in the study. All patient underwent clinical examination followed by study of macular thickness and RN FL thick ness by spectral domain Topc on OCT. The data was collected and analyzed for variations in gender and age. The data was also compared with available literature. Results: Total numbers of patients enrolled in the study were 154 (308 eyes). Numbers of males were 79 (158 eyes) and numbers of females were 75 (150 eyes). The mean age among males was 42.67 ± 12.15 years and mean age among females was 42.88 ± 11.73 years. Overall the mean mac ular thickness (central 1 mm zone) with SD - OCT was 241.75 ± 17.3 microns. The mean macular volume was 7.6 cu. mm ± 0.33. On analysis of the RNFL thickness, we observed that the RNFL was thickest in the inferior quadrant (138.58) followed by superior (122.30) nasal (116.32) and temporal quadrant (73.04). Gender-wise comparison of the data revealed no statistically significant difference for age, macular thickness parameters, volume and RFNL values except outer temporal thickness among males and females. No age-related difference was noted in the above parameters. On comparison with available norma tive data from India and elsewhere, we found significant variations with different machines. Conclusion: The study is the first to provide normative data using SD-OCT from central India. The data from spectral domain OCT correlated well with the values obtained from similar studies with SD - OCT. Values obtained from time domain OCT machines are different and are not comparable. How to cite this article: Agarwal P, Saini VK, Gupta S, Sharma A. Evaluation of Central Macular Thickness and Retinal Nerve Fiber Layer Thickness using Spectral Domain Optical Coherence Tomography in a Tertiary Care Hospital. J Curr Glaucoma Pract 2014;8(2):75-81. PMID:26997813

The vestibular nerve of the chinchilla. III. Peripheral innervation patterns in the utricular macula

NASA Technical Reports Server (NTRS)

Fernandez, C.; Goldberg, J. M.; Baird, R. A.

1990-01-01

1. Nerve fibers supplying the utricular macula of the chinchilla were labeled by extracellular injection of horseradish peroxidase into the vestibular nerve. The peripheral terminations of individual fibers were reconstructed and related to the regions of the end organ they innervated and to the sizes of their parent axons. 2. The macula is divided into medial and lateral parts by the striola, a narrow zone that runs for almost the entire length of the sensory epithelium. The striola can be distinguished from the extrastriolar regions to either side of it by the wider spacing of its hair cells. Calyx endings in the striola have especially thick walls, and, unlike similar endings in the extrastriola, many of them innervate more than one hair cell. The striola occupies 10% of the sensory epithelium; the lateral extrastriola, 50%; and the medial extrastriola, 40%. 3. The utricular nerve penetrates the bony labyrinth anterior to the end organ. Axons reaching the anterior part of the sensory epithelium run directly through the connective tissue stroma. Those supplying more posterior regions first enter a fiber layer located at the bottom of the stroma. Approximately one-third of the axons bifurcate below the epithelium, usually within 5-20 microns of the basement membrane. Bifurcations are more common in fibers destined for the extrastriola than for the striola. 4. Both calyx and bouton endings were labeled. Calyces can be simple or complex. Simple calyces innervate individual hair cells, whereas complex calyces supply 2-4 adjacent hair cells. Complex endings are more heavily concentrated in the striola than in the extrastriola. Simple calyces and boutons are found in all parts of the epithelium. Calyces emerge from the parent axon or one of its thick branches. Boutons, whether en passant or terminal, are located on thin collaterals. 5. Fibers can be classified into calyx, bouton, or dimorphic categories. The first type only has calyx endings; the second, only bouton endings; and the third, both kinds of endings. Calyx units make up 6% of the labeled fibers, bouton units less than 2%, and dimorphic units greater than 92%. The three fiber types differ in the macular zones they supply and in the diameters of their parent axons. Calyx units were restricted to the striola. The few bouton units were found in the extrastriola.(ABSTRACT TRUNCATED AT 400 WORDS).

High-Resolution Imaging of the Optic Nerve and Retina in Optic Nerve Hypoplasia

PubMed Central

Pilat, Anastasia; Sibley, Daniel; McLean, Rebecca J.; Proudlock, Frank A.; Gottlob, Irene

2015-01-01

Purpose To investigate the optic nerve and macular morphology in patients with optic nerve hypoplasia (ONH) using spectral-domain optical coherence tomography (SD OCT). Design Prospective, cross-sectional, observational study. Subjects A total of 16 participants with ONH (10 female and 6 male; mean age, 17.2 years; 6 bilateral involvement) and 32 gender-, age-, ethnicity-, and refraction-matched healthy controls. Methods High-resolution SD OCT (Copernicus [Optopol Technology S.A., Zawiercie, Poland], 3 μm resolution) and handheld SD OCT (Bioptigen Inc [Research Triangle Park, NC], 2.6 μm resolution) devices were used to acquire horizontal scans through the center of the optic disc and macula. Main Outcome Measures Horizontal optic disc/cup and rim diameters, cup depth, peripapillary retinal nerve fiber layer (RNFL), and thickness of individual retinal layers in participants with ONH and in controls. Results Patients with ONH had significantly smaller discs (P < 0.03 and P < 0.001 compared with unaffected eye and healthy controls, respectively), horizontal cup diameter (P < 0.02 for both), and cup depth (P < 0.02 and P < 0.01, respectively). In the macula, significantly thinner RNFL (nasally), ganglion cell layer (GCL) (nasally and temporally), inner plexiform layer (IPL) (nasally), outer nuclear layer (ONL) (nasally), and inner segment (centrally and temporally) were found in patients with ONH compared with the control group (P < 0.05 for all comparisons). Continuation of significantly thicker GCL, IPL, and outer plexiform layer in the central retinal area (i.e., foveal hypoplasia) was found in more than 80% of patients with ONH. Clinically unaffected fellow eyes of patients with ONH showed mild features of underdevelopment. Visual acuity and presence of septo-optic dysplasia were associated with changes in GCL and IPL. Sensitivity and specificity for the detection of ONH based on disc and retinal optical coherence tomography (OCT) parameters were >80%. Conclusions Our study provides evidence of retinal changes in ONH. In addition to thinning of retina layers mainly involving the RNFL and GCL, signs reminiscent of foveal hypoplasia were observed in patients with ONH. Optic nerve and foveal parameters measured using OCT showed high sensitivity and specificity for detecting ONH, demonstrating their useful for clinical diagnosis. PMID:25939636

Thermally Drawn Fibers as Nerve Guidance Scaffolds

PubMed Central

Koppes, Ryan A.; Park, Seongjun; Hood, Tiffany; Jia, Xiaoting; Poorheravi, Negin Abdolrahim; Achyuta, Anilkumar Harapanahalli; Fink, Yoel; Anikeeva, Polina

2016-01-01

Synthetic neural scaffolds hold promise to eventually replace nerve autografts for tissue repair following peripheral nerve injury. Despite substantial evidence for the influence of scaffold geometry and dimensions on the rate of axonal growth, systematic evaluation of these parameters remains a challenge due to limitations in materials processing. We have employed fiber drawing to engineer a wide spectrum of polymer-based neural scaffolds with varied geometries and core sizes. Using isolated whole dorsal root ganglia as an in vitro model system we have identified key features enhancing nerve growth within these fiber scaffolds. Our approach enabled straightforward integration of microscopic topography at the scale of nerve fascicles within the scaffold cores, which led to accelerated Schwann cell migration, as well as neurite growth and alignment. Our findings indicate that fiber drawing provides a scalable and versatile strategy for producing nerve guidance channels capable of controlling direction and accelerating the rate of axonal growth. PMID:26717246

Regeneration of the eighth cranial nerve in the bullfrog, Rana catesbeiana.

PubMed

Newman, A; Honrubia, V

1992-01-01

The present study was done in order to document the ability of the eighth cranial nerve of the bullfrog (Rana catesbeiana) to regenerate, the anatomic characteristics of the regenerated fibers, and the specificity of projections from individual endorgan branches of the nerve. The eighth cranial nerve was sharply transected between the ganglion cells and the brain stem in 40 healthy bullfrogs and allowed to regenerate. Anatomic studies were performed in these animals a minimum of 3 months postoperatively. Horseradish peroxidase was used to label the whole vestibular nerve or its individual endorgan branches. Labeled regenerated fibers could be identified crossing the site of the nerve section and projecting centrally to the vestibular nuclei in a pattern similar to that of normal frogs. Labeling of individual branches showed that regenerated fibers innervated the same specific areas found in normal frogs. Unlike normal animals, both thick and thin fibers projected to the medial nucleus.

Sensory and motor neuropathy in a Border Collie.

PubMed

Harkin, Kenneth R; Cash, Walter C; Shelton, G Diane

2005-10-15

A 5-month-old female Border Collie was evaluated because of progressive hind limb ataxia. The predominant clinical findings suggested a sensory neuropathy. Sensory nerve conduction velocity was absent in the tibial, common peroneal, and radial nerves and was decreased in the ulnar nerve; motor nerve conduction velocity was decreased in the tibial, common peroneal, and ulnar nerves. Histologic examination of nerve biopsy specimens revealed considerable nerve fiber depletion; some tissue sections had myelin ovoids, foamy macrophages, and axonal degeneration in remaining fibers. Marked depletion of most myelinated fibers within the peroneal nerve (a mixed sensory and motor nerve) supported the electrodiagnostic findings indicative of sensorimotor neuropathy. Progressive deterioration in motor function occurred over the following 19 months until the dog was euthanatized. A hereditary link was not established, but a littermate was similarly affected. The hereditary characteristic of this disease requires further investigation.

Improved Visualization of Glaucomatous Retinal Damage Using High-speed Ultrahigh-Resolution Optical Coherence Tomography

PubMed Central

Mumcuoglu, Tarkan; Wollstein, Gadi; Wojtkowski, Maciej; Kagemann, Larry; Ishikawa, Hiroshi; Gabriele, Michelle L.; Srinivasan, Vivek; Fujimoto, James G.; Duker, Jay S.; Schuman, Joel S.

2009-01-01

Purpose To test if improving optical coherence tomography (OCT) resolution and scanning speed improves the visualization of glaucomatous structural changes as compared with conventional OCT. Design Prospective observational case series. Participants Healthy and glaucomatous subjects in various stages of disease. Methods Subjects were scanned at a single visit with commercially available OCT (StratusOCT) and high-speed ultrahigh-resolution (hsUHR) OCT. The prototype hsUHR OCT had an axial resolution of 3.4 μm (3 times higher than StratusOCT), with an A-scan rate of 24 000 hertz (60 times faster than StratusOCT). The fast scanning rate allowed the acquisition of novel scanning patterns such as raster scanning, which provided dense coverage of the retina and optic nerve head. Main Outcome Measures Discrimination of retinal tissue layers and detailed visualization of retinal structures. Results High-speed UHR OCT provided a marked improvement in tissue visualization as compared with StratusOCT. This allowed the identification of numerous retinal layers, including the ganglion cell layer, which is specifically prone to glaucomatous damage. Fast scanning and the enhanced A-scan registration properties of hsUHR OCT provided maps of the macula and optic nerve head with unprecedented detail, including en face OCT fundus images and retinal nerve fiber layer thickness maps. Conclusion High-speed UHR OCT improves visualization of the tissues relevant to the detection and management of glaucoma. PMID:17884170

Fiber-based polarization-sensitive OCT of the human retina with correction of system polarization distortions

PubMed Central

Braaf, Boy; Vermeer, Koenraad A.; de Groot, Mattijs; Vienola, Kari V.; de Boer, Johannes F.

2014-01-01

In polarization-sensitive optical coherence tomography (PS-OCT) the use of single-mode fibers causes unpredictable polarization distortions which can result in increased noise levels and erroneous changes in calculated polarization parameters. In the current paper this problem is addressed by a new Jones matrix analysis method that measures and corrects system polarization distortions as a function of wavenumber by spectral analysis of the sample surface polarization state and deeper located birefringent tissue structures. This method was implemented on a passive-component depth-multiplexed swept-source PS-OCT system at 1040 nm which was theoretically modeled using Jones matrix calculus. High-resolution B-scan images are presented of the double-pass phase retardation, diattenuation, and relative optic axis orientation to show the benefits of the new analysis method for in vivo imaging of the human retina. The correction of system polarization distortions yielded reduced phase retardation noise, and better estimates of the diattenuation and the relative optic axis orientation in weakly birefringent tissues. The clinical potential of the system is shown by en face visualization of the phase retardation and optic axis orientation of the retinal nerve fiber layer in a healthy volunteer and a glaucoma patient with nerve fiber loss. PMID:25136498

Corneal Confocal Microscopy Detects Early Nerve Regeneration in Diabetic Neuropathy After Simultaneous Pancreas and Kidney Transplantation

PubMed Central

Tavakoli, Mitra; Mitu-Pretorian, Maria; Petropoulos, Ioannis N.; Fadavi, Hassan; Asghar, Omar; Alam, Uazman; Ponirakis, Georgios; Jeziorska, Maria; Marshall, Andy; Efron, Nathan; Boulton, Andrew J.; Augustine, Titus; Malik, Rayaz A.

2013-01-01

Diabetic neuropathy is associated with increased morbidity and mortality. To date, limited data in subjects with impaired glucose tolerance and diabetes demonstrate nerve fiber repair after intervention. This may reflect a lack of efficacy of the interventions but may also reflect difficulty of the tests currently deployed to adequately assess nerve fiber repair, particularly in short-term studies. Corneal confocal microscopy (CCM) represents a novel noninvasive means to quantify nerve fiber damage and repair. Fifteen type 1 diabetic patients undergoing simultaneous pancreas–kidney transplantation (SPK) underwent detailed assessment of neurologic deficits, quantitative sensory testing (QST), electrophysiology, skin biopsy, corneal sensitivity, and CCM at baseline and at 6 and 12 months after successful SPK. At baseline, diabetic patients had a significant neuropathy compared with control subjects. After successful SPK there was no significant change in neurologic impairment, neurophysiology, QST, corneal sensitivity, and intraepidermal nerve fiber density (IENFD). However, CCM demonstrated significant improvements in corneal nerve fiber density, branch density, and length at 12 months. Normalization of glycemia after SPK shows no significant improvement in neuropathy assessed by the neurologic deficits, QST, electrophysiology, and IENFD. However, CCM shows a significant improvement in nerve morphology, providing a novel noninvasive means to establish early nerve repair that is missed by currently advocated assessment techniques. PMID:23002037

Interdependency between mechanical parameters and afferent nerve discharge in remodeled diabetic Goto-Kakizaki rat intestine.

PubMed

Zhao, Jingbo; Yang, Jian; Liao, Donghua; Gregersen, Hans

2017-01-01

Gastrointestinal disorders are very common in diabetic patients, but the pathogenesis is still not well understood. Peripheral afferent nerves may be involved due to the complex regulation of gastrointestinal function by the enteric nervous system. We aimed to characterize the stimulus-response function of afferent fibers innervating the jejunum in the Goto-Kakizaki (GK) type 2 diabetic rat model. A key question is whether changes in afferent firing arise from remodeled tissue or from adaptive afferent processes. Seven 32-week-old male GK rats and seven age-matched normal Wistar rats were studied. Firing from mesenteric afferent nerves was recorded in excised jejunal segments of seven GK rats and seven normal Wistar rats during ramp test, stress relaxation test, and creep test. The circumferential stress-strain, spike rate increase ratio (SRIR), and single unit firing rates were calculated for evaluation of interdependency of the mechanical stimulations and the afferent nerve discharge. Elevated sensitivity to mechanical stimuli was found for diabetic nerve bundles and single unit activity ( P <0.05). The stress relaxed less in the diabetic intestinal segment ( P <0.05). Linear association between SRIR and the thickness of circumferential muscle layer was found at high stress levels as well as for SRIR and the glucose level. Altered viscoelastic properties and elevated mechanosensitivity were found in the GK rat intestine. The altered nerve signaling is related to muscle layer remodeling and glucose levels and may contribute to gastrointestinal symptoms experienced by diabetic patients.

Comparison of retinal nerve fiber layer thickness in vivo and axonal transport after chronic intraocular pressure elevation in young versus older rats.

PubMed

Abbott, Carla J; Choe, Tiffany E; Burgoyne, Claude F; Cull, Grant; Wang, Lin; Fortune, Brad

2014-01-01

To compare in young and old rats longitudinal measurements of retinal nerve fiber layer thickness (RNFLT) and axonal transport 3-weeks after chronic IOP elevation. IOP was elevated unilaterally in 2- and 9.5-month-old Brown-Norway rats by intracameral injections of magnetic microbeads. RNFLT was measured by spectral domain optical coherence tomography. Anterograde axonal transport was assessed from confocal scanning laser ophthalmolscopy of superior colliculi (SC) after bilateral intravitreal injections of cholera toxin-B-488. Optic nerve sections were graded for damage. Mean IOP was elevated in both groups (young 37, old 38 mmHg, p = 0.95). RNFL in young rats exhibited 10% thickening at 1-week (50.9±8.1 µm, p<0.05) vs. baseline (46.4±2.4 µm), then 7% thinning at 2-weeks (43.0±7.2 µm, p>0.05) and 3-weeks (43.5±4.4 µm, p>0.05), representing 20% loss of dynamic range. RNFLT in old rats showed no significant change at 1-week (44.9±4.1 µm) vs. baseline (49.2±5.3 µm), but progression to 22% thinning at 2-weeks (38.0±3.7 µm, p<0.01) and 3-weeks (40.0±6.6 µm, p<0.05), representing 59% loss of dynamic range. Relative SC fluorescence intensity was reduced in both groups (p<0.001), representing 77-80% loss of dynamic range and a severe transport deficit. Optic nerves showed 75-95% damage (p<0.001). There was greater RNFL thinning in old rats (p<0.05), despite equivalent IOP insult, transport deficit and nerve damage between age groups (all p>0.05). Chronic IOP elevation resulted in severely disrupted axonal transport and optic nerve axon damage in all rats, associated with mild RNFL loss in young rats but a moderate RNFL loss in old rats despite the similar IOP insult. Hence, the glaucomatous injury response within the RNFL depends on age.

Sensation, mechanoreceptor, and nerve fiber function after nerve regeneration.

PubMed

Krarup, Christian; Rosén, Birgitta; Boeckstyns, Michel; Ibsen Sørensen, Allan; Lundborg, Göran; Moldovan, Mihai; Archibald, Simon J

2017-12-01

Sensation is essential for recovery after peripheral nerve injury. However, the relationship between sensory modalities and function of regenerated fibers is uncertain. We have investigated the relationships between touch threshold, tactile gnosis, and mechanoreceptor and sensory fiber function after nerve regeneration. Twenty-one median or ulnar nerve lesions were repaired by a collagen nerve conduit or direct suture. Quantitative sensory hand function and sensory conduction studies by near-nerve technique, including tactile stimulation of mechanoreceptors, were followed for 2 years, and results were compared to noninjured hands. At both repair methods, touch thresholds at the finger tips recovered to 81 ± 3% and tactile gnosis only to 20 ± 4% (p < 0.001) of control. The sensory nerve action potentials (SNAPs) remained dispersed and areas recovered to 23 ± 2% and the amplitudes only to 7 ± 1% (P < 0.001). The areas of SNAPs after tactile stimulation recovered to 61 ± 11% and remained slowed. Touch sensation correlated with SNAP areas (p < 0.005) and was negatively related to the prolongation of tactile latencies (p < 0.01); tactile gnosis was not related to electrophysiological parameters. The recovered function of regenerated peripheral nerve fibers and reinnervated mechanoreceptors may differentially influence recovery of sensory modalities. Touch was affected by the number and function of regenerated fibers and mechanoreceptors. In contrast, tactile gnosis depends on the input and plasticity of the central nervous system (CNS), which may explain the absence of a direct relation between electrophysiological parameters and poor recovery. Dispersed maturation of sensory nerve fibers with desynchronized inputs to the CNS also contributes to the poor recovery of tactile gnosis. Ann Neurol 2017. Ann Neurol 2017;82:940-950. © 2017 American Neurological Association.

Comparative quantitative assessment of the human corneal sub-basal nerve plexus by in vivo confocal microscopy and histological staining.

PubMed

Kowtharapu, B S; Winter, K; Marfurt, C; Allgeier, S; Köhler, B; Hovakimyan, M; Stahnke, T; Wree, A; Stachs, O; Guthoff, R F

2017-03-01

PurposeThis study was designed to compare and contrast quantitative data of the human corneal sub-basal nerve plexus (SBP) evaluated by two different methods: in vivo confocal microscopy (IVCM), and immunohistochemical staining of ex vivo donor corneas.MethodsSeven parameters of the SBP in large-scale IVCM mosaicking images from healthy subjects were compared with the identical parameters in ex vivo donor corneas stained by β-III-tubulin immunohistochemistry. Corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), average weighted corneal nerve fiber tortuosity (CNFTo), corneal nerve connection points (CNCP), average corneal nerve single-fiber length (CNSFL), and average weighted corneal nerve fiber thickness (CNFTh) were calculated using a dedicated, published algorithm and compared.ResultsOur experiments showed significantly higher values for CNFL (50.2 vs 21.4 mm/mm 2 ), CNFD (1358.8 vs 277.3 nerve fibers/mm 2 ), CNBD (847.6 vs 163.5 branches/mm 2 ), CNFTo (0.095 vs 0.081 μm -1 ), and CNCP (49.4 vs 21.6 connections/mm 2 ) in histologically staining specimens compared with IVCM images. In contrast, CNSFL values were higher in IVCM images than in histological specimens (32.1 vs 74.1 μm). No significant difference was observed in CNFTh (2.22 vs 2.20 μm) between the two groups.ConclusionsThe results of this study have shown that IVCM has an inherently lower resolution compared with ex vivo immunohistochemical staining of the corneal SBP and that this limitation leads to a systematic underestimation of several SBP parameters. Despite this shortcoming, IVCM is a vital clinical tool for in vivo characterization, quantitative clinical imaging, and evaluation of the human corneal SBP.

Mirror-image pain after nerve reconstruction in rats is related to enhanced density of epidermal peptidergic nerve fibers.

PubMed

Kambiz, S; Brakkee, E M; Duraku, L S; Hovius, S E R; Ruigrok, T J H; Walbeehm, E T

2015-05-01

Mirror-image pain is a phenomenon in which unprovoked pain is detected on the uninjured contralateral side after unilateral nerve injury. Although it has been implicated that enhanced production of nerve growth factor (NGF) in the contralateral dorsal root ganglion is important in the development of mirror-image pain, it is not known if this is related to enhanced expression of nociceptive fibers in the contralateral skin. Mechanical and thermal sensitivity in the contralateral hind paw was measured at four different time points (5, 10, 20 and 30weeks) after transection and immediate end-to-end reconstruction of the sciatic nerve in rats. These findings were compared to the density of epidermal (peptidergic and non-peptidergic) nerve fibers on the contralateral hind paw. Mechanical hypersensitivity of the contralateral hind paw was observed at 10weeks PO, a time point in which both subgroups of epidermal nerve fibers reached control values. Thermal hypersensitivity was observed with simultaneous increase in the density of epidermal peptidergic nerve fibers of the contralateral hind paw at 20weeks PO. Both thermal sensitivity and the density of epidermal nerve fibers returned to control values 30weeks PO. We conclude that changes in skin innervation and sensitivity are present on the uninjured corresponding side in a transient pain model. Therefore, the contralateral side cannot serve as control. Moreover, the current study confirms the involvement of the peripheral nervous system in the development of mirror-image pain. Copyright © 2015 Elsevier Inc. All rights reserved.

Response properties of the refractory auditory nerve fiber.

PubMed

Miller, C A; Abbas, P J; Robinson, B K

2001-09-01

The refractory characteristics of auditory nerve fibers limit their ability to accurately encode temporal information. Therefore, they are relevant to the design of cochlear prostheses. It is also possible that the refractory property could be exploited by prosthetic devices to improve information transfer, as refractoriness may enhance the nerve's stochastic properties. Furthermore, refractory data are needed for the development of accurate computational models of auditory nerve fibers. We applied a two-pulse forward-masking paradigm to a feline model of the human auditory nerve to assess refractory properties of single fibers. Each fiber was driven to refractoriness by a single (masker) current pulse delivered intracochlearly. Properties of firing efficiency, latency, jitter, spike amplitude, and relative spread (a measure of dynamic range and stochasticity) were examined by exciting fibers with a second (probe) pulse and systematically varying the masker-probe interval (MPI). Responses to monophasic cathodic current pulses were analyzed. We estimated the mean absolute refractory period to be about 330 micros and the mean recovery time constant to be about 410 micros. A significant proportion of fibers (13 of 34) responded to the probe pulse with MPIs as short as 500 micros. Spike amplitude decreased with decreasing MPI, a finding relevant to the development of computational nerve-fiber models, interpretation of gross evoked potentials, and models of more central neural processing. A small mean decrement in spike jitter was noted at small MPI values. Some trends (such as spike latency-vs-MPI) varied across fibers, suggesting that sites of excitation varied across fibers. Relative spread was found to increase with decreasing MPI values, providing direct evidence that stochastic properties of fibers are altered under conditions of refractoriness.

Calculation and plotting of retinal nerve fiber paths based on Jansonius et al. 2009/2012 with an R program.

PubMed

Bach, M; Hoffmann, M B

2018-06-01

The data presented in this article are related to the research article entitled "Retinal conduction speed analysis reveals different origins of the P50 and N95 components of the (multifocal) pattern electroretinogram" (Bach et al., 2018) [1]. That analysis required the individual length data of the retinal nerve fibers (from ganglion cell body to optic nerve head, depending on the position of the ganglion cell body). Jansonius et al. (2009, 2012) [2,3] mathematically modeled the path morphology of the human retinal nerve fibers. We here present a working implementation with source code (for the free and open-source programming environment "R") of the Jansonius' formulas, including all errata. One file defines Jansonius et al.'s "phi" function. This function allows quantitative modelling of paths (and any measures derived from them) of the retinal nerve fibers. As a working demonstration, a second file contains a graph which plots samples of nerve fibers. The included R code runs in base R without the need of any additional packages.

Natural history of Leber's hereditary optic neuropathy: longitudinal analysis of the retinal nerve fiber layer by optical coherence tomography.

PubMed

Barboni, Piero; Carbonelli, Michele; Savini, Giacomo; Ramos, Carolina do V F; Carta, Arturo; Berezovsky, Adriana; Salomao, Solange R; Carelli, Valerio; Sadun, Alfredo A

2010-03-01

To investigate by optical coherence tomography (OCT) the topographic pattern and temporal sequence of fiber loss in the peripapillary retinal nerve fiber layer (RNFL) of patients with Leber's hereditary optic neuropathy (LHON) in a longitudinal follow-up. Cohort study. Six eyes of 4 patients with molecularly defined LHON were enrolled before the subacute period of visual loss. Subjects were studied by StratusOCT (Carl Zeiss Meditec, Inc., Dublin, CA) during a 9-month follow-up starting from the presymptomatic stage of the disease. Examinations were carried out at 4 different time points: presymptomatic stage, time of visual loss, and 3 and 9 months later. Peripapillary RNFL thickness for each quadrant of the optic nerve. Statistical comparisons were performed by ordinary analysis of variance with Dunnett's post-test. A significant increase of RNFL thickness was detected in the temporal and inferior quadrants between the presymptomatic stage and the disease onset (P<0.05). The 360-degree average and the superior and nasal quadrants showed a nonstatistically significant increase of thickness at this time. In the 360-degree average (P<0.01), superior (P<0.01), nasal (P<0.05), and inferior (P<0.01) quadrants, RNFL thickening showed statistically significant changes between the presymptomatic stage and the 3-month follow-up. At 3 months, a nonsignificant reduction of RNFL thickness was detected in the temporal quadrant. A significant reduction of RNFL was detected in all but the nasal quadrants between the presymptomatic stage and the 9-month Follow-up. The RNFL thickness increase first appeared at the temporal and inferior quadrants. Conversely, at 3 months the thickening fibers were more evident in the superior and nasal quadrants. These findings are consistent with the established preferential early involvement of the papillomacular bundle in LHON. We also demonstrated the previously unrecognized simultaneous early involvement of the inferior quadrant. The late involvement of both superior and nasal quadrants suggests a dynamic evolution of the acute stage that continues for 3 months and may represent a therapeutic window of opportunity. Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Recovery of C-fiber-induced extravasation following peripheral nerve injury in the rat.

PubMed

Bester, H; Allchorne, A J; Woolf, C J

1998-12-01

Peripheral nerve injury leads to substantial alterations in injured sensory neurons. These include cell death, phenotypic modifications, and regeneration. Primary sensory neurons have recently been shown not to die until a time beyond 4 months following a nerve crush or ligation and this loss is, moreover, limited to cells with unmyelinated axons, the C-fibers. The late loss of C-fibers may be due to a lack of target reinnervation during the regenerative phase. In order to investigate this, we have used a particular peripheral function, unique to C-fibers, as a measure of peripheral reinnervation: an increase in capillary permeability on antidromic activation of C-fibers, i.e., neurogenic extravasation. This was investigated in rats that had received a nerve crush injury 1 to 50 weeks earlier. Some recovery of the capacity of C-fibers to generate extravasation was detected at 8-10 weeks, which increased further at 12-14 weeks, and then plateaued at this level with no further recovery at 30 or 50 weeks. In intact and damaged sciatic nerves, A beta-fibers never induced extravasation. These findings are compatible with the hypothesis that those C-fibers which make it back to their peripheral targets do not subsequently die and those that do not, may die. Copyright 1998 Academic Press.

Cornea nerve fiber quantification and construction of phenotypes in patients with fibromyalgia

PubMed Central

Oudejans, Linda; He, Xuan; Niesters, Marieke; Dahan, Albert; Brines, Michael; van Velzen, Monique

2016-01-01

Cornea confocal microscopy (CCM) is a novel non-invasive method to detect small nerve fiber pathology. CCM generally correlates with outcomes of skin biopsies in patients with small fiber pathology. The aim of this study was to quantify the morphology of small nerve fibers of the cornea of patients with fibromyalgia in terms of density, length and branching and further phenotype these patients using standardized quantitative sensory testing (QST). Small fiber pathology was detected in the cornea of 51% of patients: nerve fiber length was significantly decreased in 44% of patients compared to age- and sex-matched reference values; nerve fiber density and branching were significantly decreased in 10% and 28% of patients. The combination of the CCM parameters and sensory tests for central sensitization, (cold pain threshold, mechanical pain threshold, mechanical pain sensitivity, allodynia and/or windup), yielded four phenotypes of fibromyalgia patients in a subgroup analysis: one group with normal cornea morphology without and with signs of central sensitization, and a group with abnormal cornea morphology parameters without and with signs of central sensitization. In conclusion, half of the tested fibromyalgia population demonstrates signs of small fiber pathology as measured by CCM. The four distinct phenotypes suggest possible differences in disease mechanisms and may require different treatment approaches. PMID:27006259

The blood flow in the periodontal ligament regulated by the sympathetic and sensory nerves in the cat.

PubMed

Karita, K; Izumi, H; Tabata, T; Kuriwada, S; Sasano, T; Sanjo, D

1989-01-01

This study was carried out to investigate the nervous control of the blood flow in the periodontal ligament measured by laser Doppler flowmeter. Ten adult cats were anesthetized with pentobarbital sodium (initial dose of 30 mg/kg, i.v. and maintenance dose of 5 mg/kg, i.v.). After enucleating the left eye ball, the superior alveolar nerve was exposed. The bone overlying the labial aspect of the left maxillary canine tooth root was pared away until a transparent layer of bone was left covering the periodontal ligament. A laser light from a probe of the flowmeter fixed at the tooth was beamed through the thinned bone. Three different patterns of responses were observed following the electrical stimulation of the distal end of the cut superior alveolar nerve: an increasing, a decreasing and a biphasic change of blood flow. The application of capsaicin onto the superior alveolar nerve reduced the response of blood flow increase but had no effect on the response of blood flow decrease. On the other hand, the response of blood flow decrease was completely inhibited by the pretreatment with phentolamine while the response of blood flow increase was not affected. The present results suggest that blood flow in the periodontal ligament of cats is controlled by sympathetic alpha-adrenergic fibers for vasoconstriction and by sensory fibers for vasodilation.

Subsurface optical stimulation of rat prostate cavernous nerves using a continuous wave, single mode, 1490 nm diode laser

NASA Astrophysics Data System (ADS)

Tozburun, Serhat; Stahl, Charlotte S. D.; Hutchens, Thomas C.; Lagoda, Gwen A.; Burnett, Arthur L.; Fried, Nathaniel M.

2013-03-01

Successful identification of the cavernous nerves (CN's) during radical prostatectomy requires detection of the CN's through a thin layer of overlying fascia. This study explores the 1490 nm infrared (IR) diode laser wavelength for rapid and deep subsurface CN stimulation in a rat model, in vivo. A 150-mW, 1490-nm diode laser providing an optical penetration depth of 520 μm was used to stimulate the CN's in 8 rats through a single mode fiber optic probe with 1-mm-diameter spot and 15 s irradiation time. Successful ONS was judged by an intracavernous pressure response (ICP) in the rat penis. Subsurface ONS at 1490 nm was also compared with previous studies using 1455 and 1550 nm IR diode laser wavelengths. ONS was observed through fascia layers up to 380 μm thick using an incident laser power of 50 mW. ICP response times as short as 4.6 +/- 0.2 s were recorded using higher laser powers bust still below the nerve damage threshold. The 1490-nm diode laser represents a compact, low cost, high power, and high quality infrared light source for use in ONS. This wavelength provides deeper optical penetration than 1455 nm and more rapid and efficient nerve stimulation than 1550 nm.

[Effect of electroacupuncture on the expression of oligodendrocyte precursor cells in rats with compressed spinal cord injury].

PubMed

Huang, Si-qin; Qi, Wei; Zeng, Zhi-hua; Wang, Ke-jian; Wu, Xiu-yu

2014-11-01

To investigate the effect of electroacupuncture on the expression of oligodendrocyte precursor cells in rats with compressed spinal cord injury (CSCI) and to explore the mechanism of remyelinization. Thirty-six SD rats were randomly divided into a control group and three treatment groups with 3 d, 7 d and 14 d of treatment respectively. Acupuncture was given to rats in the treatment groups through jiaji point, double zusanli (ST36), and double taixi (KI3). Electroacupuncture (continuous wave, 2 Hz/1. 5 V, 30 min) was applied for the double zusanli (ST36) and double taixi (KI3). Ethological alterations of the rats were observed with quantitative assessment of neurologic function. The ultrastructure changes of nerve fibers in white matter were determined under electronic microscope. Expressions of NG2 protein, an OPC marker, was observed by Western blot. No significant changes in neurologic function and G-ratio were observed after three days and seven days of electroacupuncture treatment (P>0. 05). However, 14 d of electroacupuncture treatment made a significant change compared to the 7 d treatment group and the control group (P<0. 05). The electronic microscope showed axons with varied degree of swollen, degenerated and lost cell organelle in axoplasm, edema in myelin sheaths, disordered, thickened and even broken layers of myelin sheaths in the rats with CSCI. The rats in the treatment groups had milder swollen axons and more compacted layers of myelin sheaths compared to their controls. Western blot showed that the expression of NG2 was increased with time and the differences among the three treatment groups were statistically significant (P<0. 05). The rats in the treatment groups also had higher expressions of NG2 than their controls at 7 d and 14 d (P<0. 05). Electroacupuncture can improve inflammation and edema in the injured nerve fibers and up regulate NG2 expression and remyelination of the injured nerve fibers in rats with CSCI.

Glaucoma diagnostic performance of GDxVCC and spectralis OCT on eyes with atypical retardation pattern.

PubMed

Hoesl, Laura Maria; Tornow, Ralf P; Schrems, Wolfgang A; Horn, Folkert K; Mardin, Christian Y; Kruse, Friedrich E; Juenemann, Anselm G M; Laemmer, Robert

2013-01-01

To investigate the impact of typical scan score (TSS) on discriminating glaucomatous and healthy eyes by scanning laser polarimetry and spectral domain optical coherence tomography (SD-OCT) in 32 peripapillary sectors. One hundred two glaucoma patients and 32 healthy controls underwent standard automated perimetry, 24-hour intraocular pressure profile, optic disc photography, GDxVCC, and SD-OCT measurements. For controls, only very typical scans (TSS=100) were accepted. Glaucoma patients were divided into 3 subgroups (very typical: TSS=100; typical: 99≥TSS≥80, atypical: TSS<80). Receiver operating characteristic curves were constructed for mean retinal nerve fiber layer values, sector data, and nerve fiber indicator (NFI). Sensitivity was estimated at ≥90% specificity to compare the discriminating ability of each imaging modality. For discrimination between healthy and glaucomatous eyes with very typical scans, the NFI and inferior sector analyses 26 to 27 demonstrated the highest sensitivity at ≥90% specificity in GDxVCC and SD-OCT, respectively. For the typical and atypical groups, sensitivity at ≥90% specificity decreased for all 32 peripapillary sectors on an average by 10.9% and 17.9% for GDxVCC and by 4.9% and 0.8% for SD-OCT. For GDxVCC, diagnostic performance of peripapillary sectors decreased with lower TSS, especially in temporosuperior and inferotemporal sectors (sensitivity at ≥90% specificity decreased by 55.3% and by 37.8% in the atypical group). Diagnostic accuracy is comparable for SD-OCT and GDxVCC if typical scans (TSS=100) are investigated. Decreasing TSS is associated with a decrease in diagnostic accuracy for discriminating healthy and glaucomatous eyes by scanning laser polarimetry. NFI is less influenced than the global or sector retinal nerve fiber layer thickness. The TSS score should be included in the standard printout. Diagnostic accuracy of SD-OCT is barely influenced by low TSS.

Determinants of peripapillary retinal nerve fiber layer thickness regarding ocular and systemic parameters - the MIPH Eye&Health Study.

PubMed

Schuster, Alexander Karl-Georg; Fischer, Joachim Ernst; Vossmerbaeumer, Christine; Vossmerbaeumer, Urs

2016-10-01

Optical coherence tomography (OCT) allows quantitative image analysis of retinal tissue in vivo. Peripapillary retinal nerve fiber layer (pRNFL) thickness is widely used for evaluation of retinal nerve fiber rarefaction in several optic neuropathies. This study evaluates associations of pRNFL thickness in healthy adult subjects in order to evaluate influencing factors. A cross-sectional study was performed in a working-age population. Only eyes without detectable ocular pathologies were included in the analysis. Among analyzed systemic cardiovascular parameters were age, gender, body-mass index, mean arterial blood pressure, HbA1c, high- and low-density-lipoproteins, and triglycerides. A comprehensive ophthalmological examination including refraction, tonometry, keratometry, and central corneal thickness measurmentwas performed. In addition, pRNFL thickness was imaged by spectral-domain OCT. Univariable and multivariable associations of pRNFL thickness in all four quadrants and on average with systemic and ocular parameters were calculated using a generalized estimating equation model. Three hundred and six subjects were included. pRNFL thickness measurements showed a significant association with spherical equivalent: pRNFL thickness decreased with increasing myopia in all quadrants (multivariable regression coefficients Beta: superior: 1.16, 95 % CI [0.62;1.71], p < 0.001; temporal: 0.87, [0.33;1.41], p = 0.001; inferior: 1.80, [1.18;2.42], p < 0.001; nasal: 2.60, [2.01;3.20], p < 0.001) and on average (1.51, [1.20;1.82], p < 0.001). A thicker central cornea thickness was related to lower pRNFL in the superior (-0.05, [-0.10; -0.01], p = 0.01), the inferior quadrant (-0.05, [-0.10;0.00], p = 0.03) and on average (-0.04, [-0.07; -0.01], p = 0.02). All other parameters were not  associated. Our findings highlight the importance of refraction when evaluating pRNFL thickness and its independence from other systemic parameters.

Imaging retinal nerve fiber bundles using optical coherence tomography with adaptive optics.

PubMed

Kocaoglu, Omer P; Cense, Barry; Jonnal, Ravi S; Wang, Qiang; Lee, Sangyeol; Gao, Weihua; Miller, Donald T

2011-08-15

Early detection of axonal tissue loss in retinal nerve fiber layer (RNFL) is critical for effective treatment and management of diseases such as glaucoma. This study aims to evaluate the capability of ultrahigh-resolution optical coherence tomography with adaptive optics (UHR-AO-OCT) for imaging the RNFL axonal bundles (RNFBs) with 3×3×3μm(3) resolution in the eye. We used a research-grade UHR-AO-OCT system to acquire 3°×3° volumes in four normal subjects and one subject with an arcuate retinal nerve fiber layer defect (n=5; 29-62years). Cross section (B-scans) and en face (C-scan) slices extracted from the volumes were used to assess visibility and size distribution of individual RNFBs. In one subject, we reimaged the same RNFBs twice over a 7month interval and compared bundle width and thickness between the two imaging sessions. Lastly we compared images of an arcuate RNFL defect acquired with UHR-AO-OCT and commercial OCT (Heidelberg Spectralis). Individual RNFBs were distinguishable in all subjects at 3° retinal eccentricity in both cross-sectional and en face views (width: 30-50μm, thickness: 10-15μm). At 6° retinal eccentricity, RNFBs were distinguishable in three of the five subjects in both views (width: 30-45μm, thickness: 20-40μm). Width and thickness RNFB measurements taken 7months apart were strongly correlated (p<0.0005). Mean difference and standard deviation of the differences between the two measurement sessions were -0.1±4.0μm (width) and 0.3±1.5μm (thickness). UHR-AO-OCT outperformed commercial OCT in terms of clarity of the microscopic retina. To our knowledge, these are the first measurements of RNFB cross section reported in the living human eye. Copyright © 2011 Elsevier Ltd. All rights reserved.

Imaging retinal nerve fiber bundles using optical coherence tomography with adaptive optics

PubMed Central

Kocaoglu, Omer P.; Cense, Barry; Jonnal, Ravi S.; Wang, Qiang; Lee, Sangyeol; Gao, Weihua; Miller, Donald T.

2011-01-01

Early detection of axonal tissue loss in retinal nerve fiber layer (RNFL) is critical for effective treatment and management of diseases such as glaucoma. This study aims to evaluate the capability of ultrahigh-resolution optical coherence tomography with adaptive optics (UHR-AO-OCT) for imaging the RNFL axonal bundles (RNFBs) with 3×3×3 μm3 resolution in the eye. We used a research-grade UHR-AO-OCT system to acquire 3°×3° volumes in four normal subjects and one subject with an arcuate retinal nerve fiber layer defect (n=5; 29–62yrs). Cross section (B-scans) and en face (C-scan) slices extracted from the volumes were used to assess visibility and size distribution of individual RNFBs. In one subject, we reimaged the same RNFBs twice over a seven month interval and compared bundle width and thickness between the two imaging sessions. Lastly we compared images of an arcuate RNFL defect acquired with UHR-AO-OCT and commercial OCT (Heidelberg Spectralis). Individual RNFBs were distinguishable in all subjects at 3° retinal eccentricity in both cross-sectional and en face views (width: 30–50μm, thickness: 10–15μm). At 6° retinal eccentricity, RNFBs were distinguishable in three of the five subjects in both views (width: 30–45μm, thickness: 20–40μm). Width and thickness RNFB measurements taken seven months apart were strongly correlated (p<0.0005). Mean difference and standard deviation of the differences between the two measurement sessions were −0.1±4.0 μm (width) and 0.3±1.5 μm (thickness). UHR-AO-OCT outperformed commercial OCT in terms of clarity of the microscopic retina. To our knowledge, these are the first measurements of RNFB cross section reported in the living human eye. PMID:21722662

An Assessment of Retinal Nerve Fiber Layer Thickness in Non-Diabetic Obese Children and Adolescents

PubMed Central

Özen, Bediz; Öztürk, Hakan; Çatlı, Gönül; Dündar, Bumin

2018-01-01

Objective: Obesity affects almost all systems in the body. This includes the retinal nerve fibers which may be damaged due to a chronic inflammatory process. To determine changes in retinal nerve fiber layer (RNFL) thickness in non-diabetic children and adolescents using optical coherence tomography (OCT) and to evaluate the relationship between this change, metabolic risk factors and pubertal stage. Methods: Thirty-eight obese and 40 healthy children and adolescents aged 10-18 years were included in the study. RNFL measurements from the optic disk and all surrounding quadrants were obtained using OCT from both eyes of the individuals in the study groups. Correlations between RNFL thickness and age, auxological measurements, pubertal stage, systolic and diastolic blood pressure, homeostasis model assessment-insulin resistance (HOMA-IR) index and lipid values were investigated. Results: A general decrease was observed in RNFL thickness in obese subjects compared to the controls, the decrease being highest in the inferior quadrant, although these differences were not statistically significant (p>0.05). RNFL thickness was negatively correlated with body mass index (BMI) standard deviation score (SDS) in both groups (control group r=-0.345, p=0.029; obese group r=-0.355, p=0.022). Significant negative correlations were determined between diastolic blood pressure, HOMA-IR, low density lipoprotein cholesterol level and RNFL thickness (r=-0.366, p=0.024; r=-0.394, p=0.016; and r=-0.374, p=0.022, respectively) in the obese group, while there was no association between these parameters and RNFL thickness in the control group. Conclusion: In this cross-sectional study, no statistically significant difference in RNFL thicknesses between the obese and control groups was determined. However, RNFL thickness was found to decrease in both healthy and obese children as BMI-SDS values increased. Further prospective studies may be of benefit to determine whether the decrease in RNFL values might become more pronounced on long-term follow-up. PMID:28739552

Retinal Nerve Fiber Layer Thickness in Children With ADHD.

PubMed

Hergüner, Arzu; Alpfidan, İsmail; Yar, Ahmet; Erdoğan, Erkan; Metin, Özge; Sakarya, Yaşar; Hergüner, Sabri

2018-05-01

The current study aims to compare retinal nerve fiber layer (RNFL) thickness, macular thickness, and macular volume between children with ADHD and a control group. The study group included children with ADHD and the control group consisted of age- and gender-matched participants without any psychiatric disorder. In all participants, RNFL thickness, macular thickness, and macular volume were measured by using spectral domain-optical coherence tomography (SD-OCT). ADHD symptom severity was evaluated by using parent-report measures, including Conners' Parent Rating Scale-Revised: Short Form (CPRS-R: S) and the Strengths and Difficulties Questionnaire: Parent Form (SDQ: P). We compared 90 eyes of 45 children with ADHD and 90 eyes of 45 controls. ADHD group had significantly lower RNFL thickness only in nasal quadrant than the controls. The remaining RNFL quadrants, macular thickness, and volume were not significantly different between groups. There was a reverse correlation between RNFL thickness and ADHD symptom severity. This is the first study examining the RNFL thickness in ADHD. Our findings showed that nasal RNFL thickness was lower, indicating reduced unmyelinated axons in the retina of children with ADHD. The results of this study support the evidence that ADHD involves a lag in cortical maturation and this is measurable in the retina.

Age, ocular magnification, and circumpapillary retinal nerve fiber layer thickness

NASA Astrophysics Data System (ADS)

Wang, Mengyu; Elze, Tobias; Li, Dian; Baniasadi, Neda; Wirkner, Kerstin; Kirsten, Toralf; Thiery, Joachim; Loeffler, Markus; Engel, Christoph; Rauscher, Franziska G.

2017-12-01

Optical coherence tomography (OCT) manufacturers graphically present circumpapillary retinal nerve fiber layer thickness (cpRNFLT) together with normative limits to support clinicians in diagnosing ophthalmic diseases. The impact of age on cpRNFLT is typically implemented by linear models. cpRNFLT is strongly location-specific, whereas previously published norms are typically restricted to coarse sectors and based on small populations. Furthermore, OCT devices neglect impacts of lens or eye size on the diameter of the cpRNFLT scan circle so that the diameter substantially varies over different eyes. We investigate the impact of age and scan diameter reported by Spectralis spectral-domain OCT on cpRNFLT in 5646 subjects with healthy eyes. We provide cpRNFLT by age and diameter at 768 angular locations. Age/diameter were significantly related to cpRNFLT on 89%/92% of the circle, respectively (pointwise linear regression), and to shifts in cpRNFLT peak locations. For subjects from age 42.1 onward but not below, increasing age significantly decreased scan diameter (r=-0.28, p<0.001), which suggests that pathological cpRNFLT thinning over time may be underestimated in elderly compared to younger subjects, as scan diameter decrease correlated with cpRNFLT increase. Our detailed numerical results may help to generate various correction models to improve diagnosing and monitoring optic neuropathies.

Evaluation of a New Scoring System for Retinal Nerve Fiber Layer Photography Using HRA1 in 964 Eyes

PubMed Central

Hong, Samin; Moon, Jong Wook; Ha, Seung Joo; Kim, Chan Yun; Seong, Gong Je

2007-01-01

Purpose To evaluate retinal nerve fiber layer (RNFL) defect by a new scoring system for RNFL photography using the Heidelberg Retina Angiograph 1 (HRA1). Methods This retrospective study included 128 healthy eyes and 836 primary open-angle glaucoma eyes. The RNFL photography using HRA1 was interpreted using a new scoring system, and correlated with visual field indices of standard automated perimetry (SAP). Using the presence of RNFL defect, darkness, width, and location, we established the new scoring system of RNFL photos. Results The mean RNFL defect score I in the early, moderate, severe, and control groups were 7.3, 9.2, 10.4, and 3.6, respectively. The mean RNFL defect score II in the early, moderate, severe, and control groups were 14.5, 28.5, 43.4, and 3.4, respectively. Correlations between the RNFL defect score II and the mean deviation of SAP was the strongest of the various combinations (r=-0.675, P<.001). Conclusions Using a new scoring system, we propose a method for semi-quantitative interpretation of RNFL photographs. This scoring system may be helpful to distinguish between normal and glaucomatous eyes, and the score is associated with the severity of visual field loss. PMID:18063886

Cellular Localization of Aquaporin-1 in the Human and Mouse Trigeminal Systems

PubMed Central

Gu, Minxia; Marshall, Charles; Ding, Jiong; Hu, Gang; Xiao, Ming

2012-01-01

Previous studies reported that a subpopulation of mouse and rat trigeminal neurons express water channel aquaporin-1 (AQP1). In this study we make a comparative investigation of AQP1 localization in the human and mouse trigeminal systems. Immunohistochemistry and immunofluorescence results showed that AQP1 was localized to the cytoplasm and cell membrane of some medium and small-sized trigeminal neurons. Additionally, AQP1 was found in numerous peripheral trigeminal axons of humans and mice. In the central trigeminal root and brain stem, AQP1 was specifically expressed in astrocytes of humans, but was restricted to nerve fibers within the central trigeminal root and spinal trigeminal tract and nucleus in mice. Furthermore, AQP1 positive nerve fibers were present in the mucosal and submucosal layers of human and mouse oral tissues, but not in the muscular and subcutaneous layers. Fluorogold retrograde tracing demonstrated that AQP1 positive trigeminal neurons innervate the mucosa but not skin of cheek. These results reveal there are similarities and differences in the cellular localization of AQP1 between the human and mouse trigeminal systems. Selective expression of AQP1 in the trigeminal neurons innervating the oral mucosa indicates an involvement of AQP1 in oral sensory transduction. PMID:23029502

Retinal nerve fiber layer thickness in normals measured by spectral domain OCT.

PubMed

Bendschneider, Delia; Tornow, Ralf P; Horn, Folkert K; Laemmer, Robert; Roessler, Christopher W; Juenemann, Anselm G; Kruse, Friedrich E; Mardin, Christian Y

2010-09-01

To determine normal values for peripapillary retinal nerve fiber layer thickness (RNFL) measured by spectral domain Optical Coherence Tomography (SOCT) in healthy white adults and to examine the relationship of RNFL with age, gender, and clinical variables. The peripapillary RNFL of 170 healthy patients (96 males and 74 females, age 20 to 78 y) was imaged with a high-resolution SOCT (Spectralis HRA+OCT, Heidelberg Engineering) in an observational cross-sectional study. RNFL thickness was measured around the optic nerve head using 16 automatically averaged, consecutive circular B-scans with 3.4-mm diameter. The automatically segmented RNFL thickness was divided into 32 segments (11.25 degrees each). One randomly selected eye per subject entered the study. Mean RNFL thickness in the study population was 97.2 ± 9.7 μm. Mean RNFL thickness was significantly negatively correlated with age (r = -0.214, P = 0.005), mean RNFL decrease per decade was 1.90 μm. As age dependency was different in different segments, age-correction of RNFL values was made for all segments separately. Age-adjusted RNFL thickness showed a significant correlation with axial length (r = -0.391, P = 0.001) and with refractive error (r = 0.396, P<0.001), but not with disc size (r = 0.124). Normal RNFL results with SOCT are comparable to those reported with time-domain OCT. In accordance with the literature on other devices, RNFL thickness measured with SOCT was significantly correlated with age and axial length. For creating a normative database of SOCT RNFL values have to be age adjusted.

Characteristics of peripapillary retinal nerve fiber layer in preterm children.

PubMed

Wang, Jingyun; Spencer, Rand; Leffler, Joel N; Birch, Eileen E

2012-05-01

To examine quantitatively characteristics of the peripapillary retinal nerve fiber layer (RNFL) in preterm children using Fourier-domain optical coherence tomography (FD-OCT). Prospective cross-sectional study. A 3-mm high-resolution FD-OCT peripapillary RNFL circular scan centered on the optic disc was obtained from right eyes of 25 preterm children (10.6 ± 3.7 years old, 8 preterm and 17 with regressed retinopathy of prematurity with normal-appearing posterior poles) and 54 full-term controls (9.8 ± 3.2 years old). Images were analyzed using Spectralis FD-OCT software to obtain average thickness measurements for 6 sectors (temporal superior, temporal, temporal inferior, nasal inferior, nasal, nasal superior), and the global average. The RNFL global average for preterm children was 8% thinner than for full-term controls. In the preterm group, peripapillary RNFL thickness on the temporal side of the disc was 6% thicker than in full-term controls, while all other peripapillary RNFL sectors were 9% to 13% thinner. In the preterm group, temporal sector peripapillary RNFL thickness was correlated with gestational age (r = -0.47, P < .001), with foveal center total thickness (r = 0.48, P = .008, 1-tailed), and with visual acuity (r = 0.42; P = .026, 1-tailed). The significantly thinner RNFL global average for preterm children suggests that prematurity is associated with subclinical optic nerve hypoplasia. Significant correlations between temporal sector RNFL thickness and both the foveal thickness and visual acuity suggest that the peripapillary RNFL is related to abnormalities in macular development as a result of preterm birth. Copyright © 2012 Elsevier Inc. All rights reserved.

Non-thermal mechanism of weak microwave fields influence on neurons

NASA Astrophysics Data System (ADS)

Shneider, M. N.; Pekker, M.

2013-09-01

A non-thermal mechanism of weak microwave field impact on a nerve fiber is proposed. It is shown that in the range of about 30-300 GHz, there are strongly pronounced resonances associated with the excitation of ultrasonic vibrations in the membrane as a result of interaction with electromagnetic radiation. The viscous dissipation limits the resonances and results in their broadening. These forced vibrations create acoustic pressure, which may lead to the redistribution of the protein transmembrane channels, and thus changing the threshold of the action potential excitation in the axons of the neural network. The influence of the electromagnetic microwave radiation on various specific areas of myelin nerve fibers was analyzed: the nodes of Ranvier, and the initial segment—the area between the neuron hillock and the first part of the axon covered with the myelin layer. It was shown that the initial segment is the most sensitive area of the myelined neurons from which the action potential normally starts.

Characteristics of eyes with inner retinal cleavage.

PubMed

Hwang, Young Hoon; Kim, Yong Yeon; Kim, Hwang Ki; Sohn, Yong Ho

2015-02-01

Inner retinal cleavage can be misdiagnosed as a glaucomatous retinal nerve fiber layer (RNFL) defect. This study was performed to characterize eyes with inner retinal cleavage. Inner retinal cleavage is defined as the appearance of a dark spindle-shaped space between the nerve fibers. Patients who presented at our institution with inner retinal cleavage were enrolled in the study. All participants were evaluated by fundus examination, visual field testing with standard automated perimetry, and optical coherence tomography (OCT) imaging. A total of 15 eyes of 11 subjects with inner retinal cleavage were included in the study. The median age of the subjects was 57 years (age range, 30-67 years). In each case, inner retinal cleavage was located adjacent to retinal blood vessels. Tissue bridging the cleavage area was observed in ten eyes. Six eyes had epiretinal membranes (ERMs), two eyes had glaucoma, and one eye had ERM in addition to glaucoma. Six eyes with inner retinal cleavage without combined ocular abnormalities had highly myopic refractive error (-6.50 to -8.50 diopters). Cross-sectional OCT images of the areas of inner retinal cleavage demonstrated defects with irregular margins and empty spaces in the inner layers of the retina. During the follow-up period, no eye showed changes in inner retinal layer cleavage or visual field sensitivity. Inner retinal cleavage was found in eyes with high myopia or ERMs. Inner retinal cleavage was associated with structural changes distinct from those associated with glaucomatous RNFL defects.

Muscle Activation During Peripheral Nerve Field Stimulation Occurs Due to Recruitment of Efferent Nerve Fibers, Not Direct Muscle Activation.

PubMed

Frahm, Ken Steffen; Hennings, Kristian; Vera-Portocarrero, Louis; Wacnik, Paul W; Mørch, Carsten Dahl

2016-08-01

Peripheral nerve field stimulation (PNFS) is a potential treatment for chronic low-back pain. Pain relief using PNFS is dependent on activation of non-nociceptive Aβ-fibers. However, PNFS may also activate muscles, causing twitches and discomfort. In this study, we developed a mathematical model, to investigate the activation of sensory and motor nerves, as well as direct muscle fiber activation. The extracellular field was estimated using a finite element model based on the geometry of CT scanned lumbar vertebrae. The electrode was modeled as being implanted to a depth of 10-15 mm. Three implant directions were modeled; horizontally, vertically, and diagonally. Both single electrode and "between-lead" stimulation between contralateral electrodes were modeled. The extracellular field was combined with models of sensory Aβ-nerves, motor neurons and muscle fibers to estimate their activation thresholds. The model showed that sensory Aβ fibers could be activated with thresholds down to 0.563 V, and the lowest threshold for motor nerve activation was 7.19 V using between-lead stimulation with the cathode located closest to the nerves. All thresholds for direct muscle activation were above 500 V. The results suggest that direct muscle activation does not occur during PNFS, and concomitant motor and sensory nerve fiber activation are only likely to occur when using between-lead configuration. Thus, it may be relevant to investigate the location of the innervation zone of the low-back muscles prior to electrode implantation to avoid muscle activation. © 2016 International Neuromodulation Society.

Research notes : can bridges have nerves? new technology developing for 'smart' infrastructure.

DOT National Transportation Integrated Search

1998-05-21

In the nerve system, the optical fibers are the information carrier and along their length are the fiber sensors, or nerve endings, which are used to sense the environment. They can be readily incorporated into new construction or retrofitted into ex...

Evaluating Glaucomatous Retinal Nerve Fiber Damage by GDx VCC Polarimetry in Taiwan Chinese Population

PubMed Central

Chen, Hsin-Yi; Huang, Mei-Ling; Huang, Wei-Cheng

2010-01-01

Purpose To study the capability of scanning laser polarimetry with variable corneal compensation (GDx VCC) to detect differences in retinal nerve fiber layer thickness between normal and glaucomatous eyes in a Taiwan Chinese population. Methods This study included 44 normal eyes and 107 glaucomatous eyes. The glaucomatous eyes were divided into three subgroups on the basis of its visual field defects (early, moderate, severe). Each subject underwent a GDx-VCC exam and visual field testing. The area under the receiver-operating characteristic curve (AROC) of each relevant parameter was used to differentiate normal from each glaucoma subgroup, respectively. The correlation between visual field index and each parameter was evaluated for the eyes in the glaucoma group. Results For normal vs. early glaucoma, the parameter with the best AROC was Nerve fiber indicator (NFI) (0.942). For normal vs. moderate glaucoma, the parameter showing the best AROC was NFI (0.985). For normal vs. severe glaucoma, the parameter that had the best AROC was NFI (1.000). For early vs. moderate glaucoma, the parameter with the best AROC was NFI (0.732). For moderate vs. severe, the parameter showing the best AROC was temporal-superior-nasal-inferior-temporal average (0.652). For early vs. severe, the parameter with the best AROC was NFI (0.852). Conclusions GDx-VCC-measured parameters may serve as a useful tool to distinguish normal from glaucomatous eyes; in particular, NFI turned out to be the best discriminating parameter.

Distribution of lymphatic tissues and autonomic nerves in supporting ligaments around the cervix uteri.

PubMed

Zhang, Jianping; Feng, Lanlan; Lu, Yi; Guo, Dongxia; Xi, Tengteng; Wang, Xiaochun

2013-05-01

To investigate the distribution of lymphatic tissues and nerves in the supporting ligaments around the cervix uteri for their tomographical relationship, 9 adult female cadavers were used in this study. Following the incision of all supporting ligaments around the cervix, hematoxylin and esosin (H&E) and immunohistochemical staining of various sections of these ligaments was performed to enable the distribution of lymph tissues and autonomic nerves to be observed. Four lymph nodes were identified in three cadaver specimens. Three lymph nodes were present at a distance of 2.0 cm from the cervix in the cranial side of the cardinal ligaments (CLs), and one lymph node was located at a distance of 4.0 cm from the cervix in the cranial side of the uterosacral ligament (USL). The lymphatic vessels were dispersed in the CLs, scattered in the cervical side of the USLs, and occasionally distributed in the vesicouterine ligaments (VULs). In the CLs, parasympathetic nerves were located at the pelvic lateral wall and went downwards and medially into the cervix, while sympathetic fibers were located in the middle and lower parts of the ligaments. In the USLs, the autonomic nerves, which consisted primarily of sympathetic fibers, went downwards and laterally from the pelvic wall to the cervix. In the VULs, parasympathetic and sympathetic nerves were located in the inner sides of the vesical veins in the deep layers of the ligaments. It is concluded that there are few lymphatic tissues in the supporting ligaments around the cervix uteri, and that nerve‑sparing radical hysterectomy (NSRH) may be a safe method for the treatment of early‑stage cervical cancer.

Recurrent laryngeal nerve alterations in developing spontaneously hypertensive rats.

PubMed

da Silva, Greice Anne Rodrigues; Mendes, Vania Alice de Aguiar; Genari, Adriana Borges; Castania, Jaci Ayrton; Salgado, Hélio Cesar; Fazan, Valéria Paula Sassoli

2016-01-01

It is well known that the recurrent laryngeal nerve not only innervates the larynx but also contains baroreceptor fibers, as demonstrated by physiological studies. Because hypertension has a negative impact on both peripheral nerve morphology and the baroreflex, we investigated the recurrent laryngeal nerve morphological alterations related to the development of hypertension. We compared morphological and morphometric aspects of different segments of the recurrent laryngeal nerve in male and female spontaneously hypertensive rats in different ages: 5, 8, and 20 weeks (n = 6 per group). Blood pressure and heart rate were recorded in anesthetized animals, followed by removal of the right and left recurrent laryngeal nerves for epoxy resin embedding and light microscopy analysis. Computer software was used for morphometric analysis. The blood pressure was significantly higher in 20-week-old animals compared to those at 5 weeks. Body weight increased significantly with age, as did the nerve fascicles. For the myelinated fibers and respective axons, there was a reduction of fiber size, more evident on the axon, associated with a reduction of the small myelinated fibers percentage in animals with high blood pressure. Also, 20-week-old animals showed a significant reduction of the blood vessel percentage of occupancy compared to younger ages. No differences were observed between genders. Hypertension development impaired axon growth, affecting mainly the small myelinated fibers. Males and females were affected equally. The alterations of the endoneural blood vessels probably played an important role on the small fibers alterations. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Fiber diameter distributions in the chinchilla's ampullary nerves

NASA Technical Reports Server (NTRS)

Hoffman, Larry F.; Honrubia, Vicente

2002-01-01

A morphometric study of the chinchilla's ampullary nerves was conducted to produce an unbiased accounting of the diameter distribution of their constituent fibers. Diameter analyses were determined from 1 microm plastic-embedded nerve sections taken at a plane immediately proximal to the sensory epithelium. We found these nerves to be composed of 2094+/-573 fibers, having diameters that ranged from 0.5 to 8 microm. The distributions of diameters were positively skewed, where approximately 75% of the fibers were found to have diameters less than 3.5 microm. An analysis of the spatial distribution of diameters within the nerve section revealed that the lateralmost areas of the nerve contained larger fractions of fibers within the smallest diameter quintiles, and the central area harbored greater proportions of the larger diameter quintiles. However, significant fractions of all quintiles were found in all areas. These data were integrated with available data of Fernandez et al. (1998) to produce diameter estimates of calyx, dimorphic, and bouton morphology subpopulations. In view of a general relationship between diameter, innervation locus, and an afferent's physiologic characteristics, these data provide the basis for developing a perspective for the in situ distribution of afferent response dynamics.

NON-INVASIVE EVALUATION OF NERVE CONDUCTION IN SMALL DIAMETER FIBERS IN THE RAT.

PubMed

Zotova, Elena G; Arezzo, Joseph C

2013-01-01

A novel non-invasive technique was applied to measure velocity within slow conducting axons in the distal extreme of the sciatic nerve (i.e., digital nerve) in a rat model. The technique is based on the extraction of rectified multiple unit activity (MUA) from in vivo whole nerve compound responses. This method reliably identifies compound action potentials in thinly myelinated fibers conducting at a range of 9-18 m/s (Aδ axons), as well as in a subgroup of unmylinated C fibers conducting at approximately 1-2 m/s. The sensitivity of the method to C-fiber conduction was confirmed by the progressive decrement of the responses in the 1-2 m/s range over a 20-day period following the topical application of capsaicin (ANOVA p <0.03). Increasing the frequency of applied repetitive stimulation over a range of 0.75 Hz to 6.0 Hz produced slowing of conduction and a significant decrease in the magnitude of the compound C-fiber response (ANOVA p <0.01). This technique offers a unique opportunity for the non-invasive, repeatable, and quantitative assessment of velocity in the subsets of Aδ and C fibers in parallel with evaluation of fast nerve conduction.

Interdependency between mechanical parameters and afferent nerve discharge in remodeled diabetic Goto-Kakizaki rat intestine

PubMed Central

Zhao, Jingbo; Yang, Jian; Liao, Donghua; Gregersen, Hans

2017-01-01

Background Gastrointestinal disorders are very common in diabetic patients, but the pathogenesis is still not well understood. Peripheral afferent nerves may be involved due to the complex regulation of gastrointestinal function by the enteric nervous system. Objective We aimed to characterize the stimulus–response function of afferent fibers innervating the jejunum in the Goto-Kakizaki (GK) type 2 diabetic rat model. A key question is whether changes in afferent firing arise from remodeled tissue or from adaptive afferent processes. Design Seven 32-week-old male GK rats and seven age-matched normal Wistar rats were studied. Firing from mesenteric afferent nerves was recorded in excised jejunal segments of seven GK rats and seven normal Wistar rats during ramp test, stress relaxation test, and creep test. The circumferential stress–strain, spike rate increase ratio (SRIR), and single unit firing rates were calculated for evaluation of interdependency of the mechanical stimulations and the afferent nerve discharge. Results Elevated sensitivity to mechanical stimuli was found for diabetic nerve bundles and single unit activity (P<0.05). The stress relaxed less in the diabetic intestinal segment (P<0.05). Linear association between SRIR and the thickness of circumferential muscle layer was found at high stress levels as well as for SRIR and the glucose level. Conclusion Altered viscoelastic properties and elevated mechanosensitivity were found in the GK rat intestine. The altered nerve signaling is related to muscle layer remodeling and glucose levels and may contribute to gastrointestinal symptoms experienced by diabetic patients. PMID:29238211

Evaluation of inner retinal layers as biomarkers in mild cognitive impairment to moderate Alzheimer’s disease

PubMed Central

Mukherjee, Dibyendu; Stinnett, Sandra S.; Cousins, Scott W.; Potter, Guy G.; Burke, James R.; Farsiu, Sina; Whitson, Heather E.

2018-01-01

Inner retina in Alzheimer's Disease (AD) may experience neuroinflammation resulting in atrophy. The objective of our study was to determine whether retinal GCIPL (ganglion cell-inner plexiform layer) or nerve fiber layer (NFL) thickness may serve as noninvasive biomarkers to diagnose AD. This cross-sectional case-control study enrolled 15 mild cognitive impairment (MCI) patients, 15 mild-moderate AD patients, and 18 cognitively normal adults. NFL and GCIPL thicknesses on optical coherence tomography (OCT) were measured using Duke Optical Coherence Tomography Retinal Analysis Program (DOCTRAP) and Spectralis software. We demonstrated that regional thicknesses of NFL or GCIPL on macular or nerve OCTs did not differ between groups. However, a multi-variate regression analysis identified macular areas with a significant thickening or thinning in NFL and GCIPL in MCI and AD patients. Our primary findings controvert previous reports of thinner NFL in moderate-to-severe AD. The areas of thickening of GCIPL and NFL in the macula adjacent to areas of thinning, as revealed by a more complex statistical model, suggest that NFL and GCIPL may undergo dynamic changes during AD progression. PMID:29420642

Ultrahigh-Speed Optical Coherence Tomography for Three-Dimensional and En Face Imaging of the Retina and Optic Nerve Head

PubMed Central

Srinivasan, Vivek J.; Adler, Desmond C.; Chen, Yueli; Gorczynska, Iwona; Huber, Robert; Duker, Jay S.; Schuman, Joel S.; Fujimoto, James G.

2009-01-01

Purpose To demonstrate ultrahigh-speed optical coherence tomography (OCT) imaging of the retina and optic nerve head at 249,000 axial scans per second and a wavelength of 1060 nm. To investigate methods for visualization of the retina, choroid, and optic nerve using high-density sampling enabled by improved imaging speed. Methods A swept-source OCT retinal imaging system operating at a speed of 249,000 axial scans per second was developed. Imaging of the retina, choroid, and optic nerve were performed. Display methods such as speckle reduction, slicing along arbitrary planes, en face visualization of reflectance from specific retinal layers, and image compounding were investigated. Results High-definition and three-dimensional (3D) imaging of the normal retina and optic nerve head were performed. Increased light penetration at 1060 nm enabled improved visualization of the choroid, lamina cribrosa, and sclera. OCT fundus images and 3D visualizations were generated with higher pixel density and less motion artifacts than standard spectral/Fourier domain OCT. En face images enabled visualization of the porous structure of the lamina cribrosa, nerve fiber layer, choroid, photoreceptors, RPE, and capillaries of the inner retina. Conclusions Ultrahigh-speed OCT imaging of the retina and optic nerve head at 249,000 axial scans per second is possible. The improvement of ∼5 to 10× in imaging speed over commercial spectral/Fourier domain OCT technology enables higher density raster scan protocols and improved performance of en face visualization methods. The combination of the longer wavelength and ultrahigh imaging speed enables excellent visualization of the choroid, sclera, and lamina cribrosa. PMID:18658089

Hypodense regions (holes) in the retinal nerve fiber layer in frequency-domain OCT scans of glaucoma patients and suspects.

PubMed

Xin, Daiyan; Talamini, Christine L; Raza, Ali S; de Moraes, Carlos Gustavo V; Greenstein, Vivienne C; Liebmann, Jeffrey M; Ritch, Robert; Hood, Donald C

2011-09-09

To better understand hypodense regions (holes) that appear in the retinal nerve fiber layer (RNFL) of frequency-domain optical coherence tomography (fdOCT) scans of patients with glaucoma and glaucoma suspects. Peripapillary circle (1.7-mm radius) and cube optic disc fdOCT scans were obtained on 208 eyes from 110 patients (57.4 ± 13.2 years) with glaucomatous optic neuropathy (GON) and 45 eyes of 45 controls (48.0 ± 12.6 years) with normal results of fundus examination. Holes in the RNFL were identified independently by two observers on the circle scans. Holes were found in 33 (16%) eyes of 28 (25%) patients; they were not found in any of the control eyes. Twenty-four eyes had more than one hole. Although some holes were relatively large, others were small. In general, the holes were located adjacent to blood vessels; only three eyes had isolated holes that were not adjacent to a vessel. The holes tended to be in the regions that are thickest in healthy controls and were associated with arcuate defects in patients. Holes were not seen in the center of the temporal disc region. They were more common in the superior (25 eyes) than in the inferior (15 eyes) disc. Of the 30 eyes with holes with reliable visual fields, seven were glaucoma suspect eyes with normal visual fields. The holes in the RNFL seen in patients with GON were probably due to a local loss of RNFL fibers and can occur in the eyes of glaucoma suspects with normal visual fields.

Neural control of renal function.

PubMed

Johns, Edward J; Kopp, Ulla C; DiBona, Gerald F

2011-04-01

The kidney is innervated with efferent sympathetic nerve fibers that directly contact the vasculature, the renal tubules, and the juxtaglomerular granular cells. Via specific adrenoceptors, increased efferent renal sympathetic nerve activity decreases renal blood flow and glomerular filtration rate, increases renal tubular sodium and water reabsorption, and increases renin release. Decreased efferent renal sympathetic nerve activity produces opposite functional responses. This integrated system contributes importantly to homeostatic regulation of sodium and water balance under physiological conditions and to pathological alterations in sodium and water balance in disease. The kidney contains afferent sensory nerve fibers that are located primarily in the renal pelvic wall where they sense stretch. Stretch activation of these afferent sensory nerve fibers elicits an inhibitory renorenal reflex response wherein the contralateral kidney exhibits a compensatory natriuresis and diuresis due to diminished efferent renal sympathetic nerve activity. The renorenal reflex coordinates the excretory function of the two kidneys so as to facilitate homeostatic regulation of sodium and water balance. There is a negative feedback loop in which efferent renal sympathetic nerve activity facilitates increases in afferent renal nerve activity that in turn inhibit efferent renal sympathetic nerve activity so as to avoid excess renal sodium retention. In states of renal disease or injury, there is activation of afferent sensory nerve fibers that are excitatory, leading to increased peripheral sympathetic nerve activity, vasoconstriction, and increased arterial pressure. Proof of principle studies in essential hypertensive patients demonstrate that renal denervation produces sustained decreases in arterial pressure. © 2011 American Physiological Society. Compr Physiol 1:699-729, 2011.

Neuropeptide Y in the adult and fetal human pineal gland.

PubMed

Møller, Morten; Phansuwan-Pujito, Pansiri; Badiu, Corin

2014-01-01

Neuropeptide Y was isolated from the porcine brain in 1982 and shown to be colocalized with noradrenaline in sympathetic nerve terminals. The peptide has been demonstrated to be present in sympathetic nerve fibers innervating the pineal gland in many mammalian species. In this investigation, we show by use of immunohistochemistry that neuropeptide Y is present in nerve fibers of the adult human pineal gland. The fibers are classical neuropeptidergic fibers endowed with large boutons en passage and primarily located in a perifollicular position with some fibers entering the pineal parenchyma inside the follicle. The distance from the immunoreactive terminals to the pinealocytes indicates a modulatory function of neuropeptide Y for pineal physiology. Some of the immunoreactive fibers might originate from neurons located in the brain and be a part of the central innervation of the pineal gland. In a series of human fetuses, neuropeptide Y-containing nerve fibers was present and could be detected as early as in the pineal of four- to five-month-old fetuses. This early innervation of the human pineal is different from most rodents, where the innervation starts postnatally.

Neuropeptide Y in the Adult and Fetal Human Pineal Gland

PubMed Central

Møller, Morten; Phansuwan-Pujito, Pansiri

2014-01-01

Neuropeptide Y was isolated from the porcine brain in 1982 and shown to be colocalized with noradrenaline in sympathetic nerve terminals. The peptide has been demonstrated to be present in sympathetic nerve fibers innervating the pineal gland in many mammalian species. In this investigation, we show by use of immunohistochemistry that neuropeptide Y is present in nerve fibers of the adult human pineal gland. The fibers are classical neuropeptidergic fibers endowed with large boutons en passage and primarily located in a perifollicular position with some fibers entering the pineal parenchyma inside the follicle. The distance from the immunoreactive terminals to the pinealocytes indicates a modulatory function of neuropeptide Y for pineal physiology. Some of the immunoreactive fibers might originate from neurons located in the brain and be a part of the central innervation of the pineal gland. In a series of human fetuses, neuropeptide Y-containing nerve fibers was present and could be detected as early as in the pineal of four- to five-month-old fetuses. This early innervation of the human pineal is different from most rodents, where the innervation starts postnatally. PMID:24757681

An autologously generated platelet-rich plasma suturable membrane may enhance peripheral nerve regeneration after neurorraphy in an acute injury model of sciatic nerve neurotmesis.

PubMed

Giannessi, Elisabetta; Coli, Alessandra; Stornelli, Maria Rita; Miragliotta, Vincenzo; Pirone, Andrea; Lenzi, Carla; Burchielli, Silvia; Vozzi, Giovanni; De Maria, Carmelo; Giorgetti, Margherita

2014-11-01

The aim of this study was to investigate the ability of suturable platelet-rich plasma (PRP) membrane to promote peripheral nerve regeneration after neurotmesis and neurorraphy. A total of 36 rats were used: 32 animals underwent surgery and were split in two groups. An interim sacrifice was performed at 6 weeks postsurgery and final sacrifice at 12 weeks; four animals did not sustain nerve injury and served as control. Clinical, electromyographic (EMG), gross, and histological changes were assessed. The EMG signal was evaluated for its amplitude and frequency spectrum. Number of regenerating fibers, their diameter, and myelin thickness were histologically analyzed. Both EMG parameters showed a significant (p < 0.05) effect of treatment at 6 and 12 weeks postsurgery. At 6 weeks, the fiber density was statistically different between treated and untreated animals with a higher observed density in treated nerves. No difference in fiber density was observed at 12 weeks postsurgery. The distribution of fiber diameters showed an effect at 12 weeks when only the sections of the nerves sutured with PRP showed fibers with diameters greater than 6 µm. Our data show that the application of a PRP fibrin membrane around the neurorraphy improves the nerve regeneration process in a rat sciatic nerve model. The use of PRP as a suturable membrane could perform an action not only as a source of bioactive proteins but also as a nerve guide to hold the scar reaction and thus improve axonal regeneration. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Small fiber neuropathy in Parkinson's disease: A clinical, pathological and corneal confocal microscopy study.

PubMed

Kass-Iliyya, Lewis; Javed, Saad; Gosal, David; Kobylecki, Christopher; Marshall, Andrew; Petropoulos, Ioannis N; Ponirakis, Georgios; Tavakoli, Mitra; Ferdousi, Maryam; Chaudhuri, Kallol Ray; Jeziorska, Maria; Malik, Rayaz A; Silverdale, Monty A

2015-12-01

Autonomic and somatic denervation is well established in Parkinson's disease (PD). (1) To determine whether corneal confocal microscopy (CCM) can non-invasively demonstrate small nerve fiber damage in PD. (2) To identify relationships between corneal nerve parameters, intraepidermal nerve fiber density (IENFD) and clinical features of PD. Twenty-six PD patients and 26 controls underwent CCM of both eyes. 24/26 PD patients and 10/26 controls underwent skin biopsies from the dorsa of both feet. PD patients underwent assessment of parasympathetic function [deep breathing heart rate variability (DB-HRV)], autonomic symptoms [scale for outcomes in Parkinson's disease - autonomic symptoms (SCOPA-AUT)], motor symptoms [UPDRS-III "ON"] and cumulative Levodopa dose. PD patients had significantly reduced corneal nerve fiber density (CNFD) with increased corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL) compared to controls. CNBD and CNFL but not CNFD correlated inversely with UPDRS-III and SCOPA-AUT. All CCM parameters correlated strongly with DB-HRV. There was no correlation between CCM parameters and disease duration, cumulative Levodopa dose or pain. IENFD was significantly reduced in PD compared to controls and correlated with CNFD and UPDRS-III. However, unlike CCM measures, IENFD correlated with disease duration and cumulative Levodopa dose but not with autonomic dysfunction. CCM identifies corneal nerve fiber pathology, which correlates with autonomic symptoms, parasympathetic deficits and motor scores in patients with PD. IENFD is also reduced and correlates with CNFD and motor symptoms but not parasympathetic deficits, indicating it detects different aspects of peripheral nerve pathology in PD. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Retinal ganglion cell damage in an experimental rodent model of blast-mediated traumatic brain injury.

PubMed

Mohan, Kabhilan; Kecova, Helga; Hernandez-Merino, Elena; Kardon, Randy H; Harper, Matthew M

2013-05-15

To evaluate retina and optic nerve damage following experimental blast injury. Healthy adult mice were exposed to an overpressure blast wave using a custom-built blast chamber. The effects of blast exposure on retina and optic nerve function and structure were evaluated using the pattern electroretinogram (pERG), spectral domain optical coherence tomography (OCT), and the chromatic pupil light reflex. Assessment of the pupil response to light demonstrated decreased maximum pupil constriction diameter in blast-injured mice using red light or blue light stimuli 24 hours after injury compared with baseline in the eye exposed to direct blast injury. A decrease in the pupil light reflex was not observed chronically following blast exposure. We observed a biphasic pERG decrease with the acute injury recovering by 24 hours postblast and the chronic injury appearing at 4 months postblast injury. Furthermore, at 3 months following injury, a significant decrease in the retinal nerve fiber layer was observed using OCT compared with controls. Histologic analysis of the retina and optic nerve revealed punctate regions of reduced cellularity in the ganglion cell layer and damage to optic nerves. Additionally, a significant upregulation of proteins associated with oxidative stress was observed acutely following blast exposure compared with control mice. Our study demonstrates that decrements in retinal ganglion cell responses can be detected after blast injury using noninvasive functional and structural tests. These objective responses may serve as surrogate tests for higher CNS functions following traumatic brain injury that are difficult to quantify.

Recovery of the sub-basal nerve plexus and superficial nerve terminals after corneal epithelial injury in mice.

PubMed

Downie, Laura E; Naranjo Golborne, Cecilia; Chen, Merry; Ho, Ngoc; Hoac, Cam; Liyanapathirana, Dasun; Luo, Carol; Wu, Ruo Bing; Chinnery, Holly R

2018-06-01

Our aim was to compare regeneration of the sub-basal nerve plexus (SBNP) and superficial nerve terminals (SNT) following corneal epithelial injury. We also sought to compare agreement when quantifying nerve parameters using different image analysis techniques. Anesthetized, female C57BL/6 mice received central 1-mm corneal epithelial abrasions. Four-weeks post-injury, eyes were enucleated and processed for PGP9.5 to visualize the corneal nerves using wholemount immunofluorescence staining and confocal microscopy. The percentage area of the SBNP and SNT were quantified using: ImageJ automated thresholds, ImageJ manual thresholds and manual tracings in NeuronJ. Nerve sum length was quantified using NeuronJ and Imaris. Agreement between methods was considered with Bland-Altman analyses. Four-weeks post-injury, the sum length of nerve fibers in the SBNP, but not the SNT, was reduced compared with naïve eyes. In the periphery, but not central cornea, of both naïve and injured eyes, nerve fiber lengths in the SBNP and SNT were strongly correlated. For quantifying SBNP nerve axon area, all image analysis methods were highly correlated. In the SNT, there was poor correlation between manual methods and auto-thresholding, with a trend towards underestimating nerve fiber area using auto-thresholding when higher proportions of nerve fibers were present. In conclusion, four weeks after superficial corneal injury, there is differential recovery of epithelial nerve axons; SBNP sum length is reduced, however the sum length of SNTs is similar to naïve eyes. Care should be taken when selecting image analysis methods to compare nerve parameters in different depths of the corneal epithelium due to differences in background autofluorescence. Copyright © 2018 Elsevier Ltd. All rights reserved.

The effect of aging on the density of the sensory nerve fiber innervation of bone and acute skeletal pain.

PubMed

Jimenez-Andrade, Juan M; Mantyh, William G; Bloom, Aaron P; Freeman, Katie T; Ghilardi, Joseph R; Kuskowski, Michael A; Mantyh, Patrick W

2012-05-01

As humans age there is a decline in most sensory systems including vision, hearing, taste, smell, and tactile acuity. In contrast, the frequency and severity of musculoskeletal pain generally increases with age. To determine whether the density of sensory nerve fibers that transduce skeletal pain changes with age, calcitonin gene related peptide (CGRP) and neurofilament 200 kDa (NF200) sensory nerve fibers that innervate the femur were examined in the femurs of young (4-month-old), middle-aged (13-month-old) and old (36-month-old) male F344/BNF1 rats. Whereas the bone quality showed a significant age-related decline, the density of CGRP(+) and NF200(+) nerve fibers that innervate the bone remained remarkably unchanged as did the severity of acute skeletal fracture pain. Thus, while bone mass, quality, and strength undergo a significant decline with age, the density of sensory nerve fibers that transduce noxious stimuli remain largely intact. These data may in part explain why musculoskeletal pain increases with age. Copyright © 2012 Elsevier Inc. All rights reserved.

Some Observations on the Fine Structure of the Giant Nerve Fibers of the Earthworm, Eisenia foetida

PubMed Central

Hama, Kiyoshi

1959-01-01

Sectioned dorsal giant fibers of the earthworm Eisenia foetida have been studied with the electron microscope. The giant axon is surrounded by a Schwannian sheath in which the lamellae are arranged spirally. They can be traced from the outer surface of the Schwann cell to the axon-Schwann membranes. Irregularities in the spiral arrangement are frequently observed. Desmosome-like attachment areas occur on the giant fiber nerve sheath. These structures appear to be arranged bilaterally in columns which are oriented slightly obliquely to the long axis of the giant fiber and aligned linearly from the axon to the periphery of the sheath. At these sites they bind together apposing portions of Schwann cell membrane comprising the sheath. Longitudinal or oblique sections of the nerve sheath attachment areas are reminiscent of the Schmidt-Lantermann clefts of vertebrate peripheral nerve. Septa of the giant fibers have been examined. They are symmetrical or non-polarized and consist of the two plasma membranes of adjacent nerve units. Characteristic vesicular and tubular structures are associated with both cytoplasmic surfaces of these septa. PMID:13673048

Collateral development and spinal motor reorganization after nerve injury and repair

PubMed Central

Yu, Youlai; Zhang, Peixun; Han, Na; Kou, Yuhui; Yin, Xiaofeng; Jiang, Baoguo

2016-01-01

Functional recovery is often unsatisfactory after severe extended nerve defects or proximal nerve trunks injuries repaired by traditional repair methods, as the long regeneration distance for the regenerated axons to reinnervate their original target end-organs. The proximal nerve stump can regenerate with many collaterals that reinnervate the distal stump after peripheral nerve injury, it may be possible to use nearby fewer nerve fibers to repair more nerve fibers at the distal end to shorten the regenerating distance. In this study, the proximal peroneal nerve was used to repair both the distal peroneal and tibial nerve. The number and location of motor neurons in spinal cord as well as functional and morphological recovery were assessed at 2 months, 4 months and 8 months after nerve repair, respectively. Projections from the intact peroneal and tibial nerves were also studied in normal animals. The changes of motor neurons were assessed using the retrograde neurotracers FG and DiI to backlabel motor neurons that regenerate axons into two different pathways. To evaluate the functional recovery, the muscle forces and sciatic function index were examined. The muscles and myelinated axons were assessed using electrophysiology and histology. The results showed that all labeled motor neurons after nerve repair were always confined within the normal peroneal nerve pool and nearly all the distribution of motor neurons labeled via distal different nerves was disorganized as compared to normal group. However, there was a significant decline in the number of double labeled motor neurons and an obvious improvement with respect to the functional and morphological recovery between 2 and 8 months. In addition, the tibial/peroneal motor neuron number ratio at different times was 2.11±0.05, 2.13±0.08, 2.09±0.12, respectively, and was close to normal group (2.21±0.09). Quantitative analysis showed no significant morphological differences between myelinated nerve fibers regenerated along the two distal nerves except for the number of nerve fibers, which was higher in the tibial nerve. The ratio of distal regenerated axon numbers to proximal donor nerve axon numbers was about 3.95±0.10, 4.06±0.19 and 3.87±0.23, respectively. This study demonstrated that fewer nerve fibers can regenerate a large number of collaterals which successfully repopulate both distal nerves and lead to the partial recovery of lost functions. It may provide a new method to repair severe extended nerve defects or proximal nerve trunks injuries. PMID:27508011

Diagnostic Performance of Peripapillary Retinal Nerve Fiber Layer Thickness for Detection of Glaucoma in an Elderly Population: The ALIENOR Study.

PubMed

Schweitzer, Cedric; Korobelnik, Jean-Francois; Le Goff, Melanie; Rahimian, Olivier; Malet, Florence; Rougier, Marie-Benedicte; Delyfer, Marie-Noelle; Dartigues, Jean-Francois; Delcourt, Cecile

2016-11-01

To assess diagnostic accuracy of spectral-domain optical coherence tomography (SD-OCT) to discriminate glaucoma and control subjects in an elderly population. The antioxidants, essential lipids, nutrition and ocular maladies study (ALIENOR: "Antioxydants, Lipides Essentiels, Nutrition et Maladies Oculaires") is a population-based study. From 2009 to 2010, a total of 624 subjects, aged 74 years or older underwent a complete eye examination, including optic disc color photography and SD-OCT examination of the macula and the optic nerve head. Glaucoma diagnosis was made using retinophotography of the optic nerve head and International Society for Epidemiologic and Geographical Ophthalmology criteria. Average and sectorial peripapillary retinal nerve fiber layer thicknesses (RNFLT) were compared between glaucoma and control subjects using area under the receiver operating characteristic curves (AUC), positive and negative likelihood ratios (LR+/LR-), and diagnostic odds ratios (DOR). A total of 532 subjects had complete data, 492 were classified as controls and 40 were classified as glaucoma. Mean age was 82.1 ± 4.2 years and average RNFLT was significantly different between both groups (controls: 88.7 ± 12.2 μm, glaucoma: 65.4 ± 14.4 μm, P < 0.001). Highest AUC values were observed for average (0.895), temporal-inferior (0.874), and temporal-superior (0.868) RNFLT. Temporal-superior RNFLT had the highest DOR (25.31; LR+, 4.65; LR-, 0.18), followed by average RNFLT (DOR: 24.80; LR+, 6.36; LR-, 0.26). When using the normative database provided by the machine, DOR increased to 31.03 (LR+, 1.75; LR-, 0.06) if at least one parameter was considered abnormal (at P < 0.05). Parameters of SD-OCT RNFL may provide valuable information in a screening strategy to improve glaucoma detection in a general population of elderly people.

The influence of corneal astigmatism on retinal nerve fiber layer thickness and optic nerve head parameter measurements by spectral-domain optical coherence tomography

PubMed Central

2012-01-01

Background To evaluate the influence of corneal astigmatism (CA) on retinal nerve fiber layer (RNFL) thickness and optic nerve head(ONH) parameters measured with spectral-domain optical coherence tomography (OCT) in high myopes patients before refractive surgery. Methods Seventy eyes of 35 consecutive refractive surgery candidates were included in this study. The mean age of the subjects was 26.42 ± 6.95 years, the average CA was −1.17 diopters (D; SD 0.64; range −0.2 to-3.3D), All subjects in this study were WTR CA. 34 eyes were in the normal CA group with a mean CA was −0.67 ± 0.28D, 36 eyes were in the high CA group with an average CA of −1.65 ± 0.49D. All subjects underwent ophthalmic examination and imaging with the Cirrus HD OCT. Results No significant difference was noted in the average cup-to-disk ratio, vertical cup-to-disk ratio and cup volume (all P values > 0.05). Compared with the normal CA group, the high CA group had a larger disc area and rim area, thinner RNFL thickness in the temporal quadrant, and the superotemporal and inferotemporal peaks were farther to the temporal horizon (All P values < 0.05). There were no significant differences between the two groups in global average RNFL thickness, as well as superior, nasal and inferior quadrant RNFL thickness (all P values > 0.05). Conclusions The degree of with-the-rule CA should be considered when interpreting ONH parameters and peripapillary RNFL thickness measured by the Cirrus HD OCT. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1148475676881895 PMID:22621341

Transplantation of Human Neural Progenitor Cells Expressing IGF-1 Enhances Retinal Ganglion Cell Survival

PubMed Central

Guo, Caiwei; Sun, Yu; Liao, Tiffany; Beattie, Ursula; López, Francisco J.; Chen, Dong Feng; Lashkari, Kameran

2015-01-01

We have previously characterized human neuronal progenitor cells (hNP) that can adopt a retinal ganglion cell (RGC)-like morphology within the RGC and nerve fiber layers of the retina. In an effort to determine whether hNPs could be used a candidate cells for targeted delivery of neurotrophic factors (NTFs), we evaluated whether hNPs transfected with an vector that expresses IGF-1 in the form of a fusion protein with tdTomato (TD), would increase RGC survival in vitro and confer neuroprotective effects in a mouse model of glaucoma. RGCs co-cultured with hNPIGF-TD cells displayed enhanced survival, and increased neurite extension and branching as compared to hNPTD or untransfected hNP cells. Application of various IGF-1 signaling blockers or IGF-1 receptor antagonists abrogated these effects. In vivo, using a model of glaucoma we showed that IOP elevation led to reductions in retinal RGC count. In this model, evaluation of retinal flatmounts and optic nerve cross sections indicated that only hNPIGF-TD cells effectively reduced RGC death and showed a trend to improve optic nerve axonal loss. RT-PCR analysis of retina lysates over time showed that the neurotrophic effects of IGF-1 were also attributed to down-regulation of inflammatory and to some extent, angiogenic pathways. This study shows that neuronal progenitor cells that hone into the RGC and nerve fiber layers may be used as vehicles for local production and delivery of a desired NTF. Transplantation of hNPIGF-TD cells improves RGC survival in vitro and protects against RGC loss in a rodent model of glaucoma. Our findings have provided experimental evidence and form the basis for applying cell-based strategies for local delivery of NTFs into the retina. Application of cell-based delivery may be extended to other disease conditions beyond glaucoma. PMID:25923430

Diagnostic Ability of Wide-field Retinal Nerve Fiber Layer Maps Using Swept-Source Optical Coherence Tomography for Detection of Preperimetric and Early Perimetric Glaucoma.

PubMed

Lee, Won June; Na, Kyeong Ik; Kim, Young Kook; Jeoung, Jin Wook; Park, Ki Ho

2017-06-01

To evaluate the diagnostic ability of wide-field retinal nerve fiber layer (RNFL) maps with swept-source optical coherence tomography (SS-OCT) for detection of preperimetric (PPG) and early perimetric glaucoma (EG). One hundred eighty-four eyes, including 67 healthy eyes, 43 eyes with PPG, and 74 eyes with EG, were analyzed. Patients underwent a comprehensive ocular examination including red-free RNFL photography, visual field testing and wide-field SS-OCT scanning (DRI-OCT-1 Atlantis; Topcon, Tokyo, Japan). SS-OCT provides a wide-field RNFL thickness map and a SuperPixel map, which are composed of the RNFL deviation map of the peripapillary area and the deviation map of the composition of the ganglion cell layer with the inner plexiform layer and RNFL (GC-IPL+RNFL) in the macular area. The ability to discriminate PPG and EG from healthy eyes was assessed using sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) for all parameters and criteria provided by the wide-field SS-OCT scan. The wide-field RNFL thickness map using SS-OCT showed the highest sensitivity of PPG-diagnostic and EG-diagnostic performance compared with the other SS-OCT criteria based on the internal normative base (93.0 and 97.3%, respectively). Among the SS-OCT continuous parameters, the RFNL thickness of the 7 clock-hour, inferior and inferotemporal macular ganglion cell analyses showed the largest AUC of PPG-diagnostic and EG-diagnostic performance (AUC=0.809 to 0.865). The wide-field RNFL thickness map using SS-OCT performed well in distinguishing eyes with PPG and EG from healthy eyes. In the clinical setting, wide-field RNFL maps of SS-OCT can be useful tools for detection of early-stage glaucoma.

Diagnostic power of optic disc morphology, peripapillary retinal nerve fiber layer thickness, and macular inner retinal layer thickness in glaucoma diagnosis with fourier-domain optical coherence tomography.

PubMed

Huang, Jehn-Yu; Pekmezci, Melike; Mesiwala, Nisreen; Kao, Andrew; Lin, Shan

2011-02-01

To evaluate the capability of the optic disc, peripapillary retinal nerve fiber layer (P-RNFL), macular inner retinal layer (M-IRL) parameters, and their combination obtained by Fourier-domain optical coherent tomography (OCT) in differentiating a glaucoma suspect from perimetric glaucoma. Two hundred and twenty eyes from 220 patients were enrolled in this study. The optic disc morphology, P-RNFL, and M-IRL were assessed by the Fourier-domain OCT (RTVue OCT, Model RT100, Optovue, Fremont, CA). A linear discriminant function was generated by stepwise linear discriminant analysis on the basis of OCT parameters and demographic factors. The diagnostic power of these parameters was evaluated with receiver operating characteristic (ROC) curve analysis. The diagnostic power in the clinically relevant range (specificity ≥ 80%) was presented as the partial area under the ROC curve (partial AROC). The individual OCT parameter with the largest AROC and partial AROC in the high specificity (≥ 80%) range were cup/disc vertical ratio (AROC = 0.854 and partial AROC = 0.142) for the optic disc parameters, average thickness (AROC = 0.919 and partial AROC = 0.147) for P-RNFL parameters, inferior hemisphere thickness (AROC = 0.871 and partial AROC = 0.138) for M-IRL parameters, respectively. The linear discriminant function further enhanced the ability in detecting perimetric glaucoma (AROC = 0.970 and partial AROC = 0.172). Average P-RNFL thickness is the optimal individual OCT parameter to detect perimetric glaucoma. Simultaneous evaluation on disc morphology, P-RNFL, and M-IRL thickness can improve the diagnostic accuracy in diagnosing glaucoma.

Automated Segmentation Errors When Using Optical Coherence Tomography to Measure Retinal Nerve Fiber Layer Thickness in Glaucoma.

PubMed

Mansberger, Steven L; Menda, Shivali A; Fortune, Brad A; Gardiner, Stuart K; Demirel, Shaban

2017-02-01

To characterize the error of optical coherence tomography (OCT) measurements of retinal nerve fiber layer (RNFL) thickness when using automated retinal layer segmentation algorithms without manual refinement. Cross-sectional study. This study was set in a glaucoma clinical practice, and the dataset included 3490 scans from 412 eyes of 213 individuals with a diagnosis of glaucoma or glaucoma suspect. We used spectral domain OCT (Spectralis) to measure RNFL thickness in a 6-degree peripapillary circle, and exported the native "automated segmentation only" results. In addition, we exported the results after "manual refinement" to correct errors in the automated segmentation of the anterior (internal limiting membrane) and the posterior boundary of the RNFL. Our outcome measures included differences in RNFL thickness and glaucoma classification (i.e., normal, borderline, or outside normal limits) between scans with automated segmentation only and scans using manual refinement. Automated segmentation only resulted in a thinner global RNFL thickness (1.6 μm thinner, P < .001) when compared to manual refinement. When adjusted by operator, a multivariate model showed increased differences with decreasing RNFL thickness (P < .001), decreasing scan quality (P < .001), and increasing age (P < .03). Manual refinement changed 298 of 3486 (8.5%) of scans to a different global glaucoma classification, wherein 146 of 617 (23.7%) of borderline classifications became normal. Superior and inferior temporal clock hours had the largest differences. Automated segmentation without manual refinement resulted in reduced global RNFL thickness and overestimated the classification of glaucoma. Differences increased in eyes with a thinner RNFL thickness, older age, and decreased scan quality. Operators should inspect and manually refine OCT retinal layer segmentation when assessing RNFL thickness in the management of patients with glaucoma. Copyright © 2016 Elsevier Inc. All rights reserved.

Normative Database and Color-code Agreement of Peripapillary Retinal Nerve Fiber Layer and Macular Ganglion Cell-inner Plexiform Layer Thickness in a Vietnamese Population.

PubMed

Perez, Claudio I; Chansangpetch, Sunee; Thai, Andy; Nguyen, Anh-Hien; Nguyen, Anwell; Mora, Marta; Nguyen, Ngoc; Lin, Shan C

2018-06-05

Evaluate the distribution and the color probability codes of the peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL) thickness in a healthy Vietnamese population and compare them with the original color-codes provided by the Cirrus spectral domain OCT. Cross-sectional study. We recruited non-glaucomatous Vietnamese subjects and constructed a normative database for peripapillary RNFL and macular GCIPL thickness. The probability color-codes for each decade of age were calculated. We evaluated the agreement with Kappa coefficient (κ) between OCT color probability codes with Cirrus built-in original normative database and the Vietnamese normative database. 149 eyes of 149 subjects were included. The mean age of enrollees was 60.77 (±11.09) years, with a mean spherical equivalent of +0.65 (±1.58) D and mean axial length of 23.4 (±0.87) mm. Average RNFL thickness was 97.86 (±9.19) microns and average macular GCIPL was 82.49 (±6.09) microns. Agreement between original and adjusted normative database for RNFL was fair for average and inferior quadrant (κ=0.25 and 0.2, respectively); and good for other quadrants (range: κ=0.63-0.73). For macular GCIPL κ agreement ranged between 0.39 and 0.69. After adjusting with the normative Vietnamese database, the percent of yellow and red color-codes increased significantly for peripapillary RNFL thickness. Vietnamese population has a thicker RNFL in comparison with Cirrus normative database. This leads to a poor color-code agreement in average and inferior quadrant between the original and adjusted database. These findings should encourage to create a peripapillary RNFL normative database for each ethnicity.

Inner retinal thinning after Brilliant Blue G-assisted internal limiting membrane peeling for vitreoretinal interface disorders.

PubMed

Ambiya, Vikas; Goud, Abhilash; Khodani, Mitali; Chhablani, Jay

2017-04-01

The aim of this study was to evaluate ganglion cell layer and nerve fiber layer thickness after Brilliant Blue G (BBG)-assisted internal limiting membrane (ILM) peeling for vitreomacular disorders. Retrospective analysis of spectral domain optical coherence tomography (SD-OCT) of 42 eyes of 42 patients, who underwent pars plana vitrectomy with BBG-assisted ILM peeling, was performed. Inclusion criteria were idiopathic macular hole, idiopathic vitreomacular traction, and idiopathic epiretinal membrane. Key exclusion criteria were vitreoretinal interface abnormalities secondary to any other diseases, follow-up period of less than 3 months, and any other associated retinal pathology. Average, minimum, and sectoral ganglion cell, and inner plexiform layers (GCIPL) and retinal nerve fiber layer (RNFL) parameters were collected. Changes in these parameters from baseline to 3- and 6-month visits after surgery were analyzed. At 3 months after surgery, we found a statistically significant reduction in the average GCIPL thickness (P = 0.031) and also in the superior sectors (P < 0.05) compared to the baseline values. A similar reduction was observed in the minimum RNFL thickness (P = 0.028) as well as in the superior sectoral RNFL thickness (P < 0.05). In 14 eyes with 6 months of follow-up, a similar statistically significant thinning of the GCIPL and RNFL was observed. However, the difference between the 3-month and 6-month values was not statistically significant (P = 0.679). BBG-assisted ILM peeling for vitreomacular interface disorders leads to thinning of the inner retina including GCIPL and RNFL. These structural changes should be correlated with retinal function tests to explore the pros and cons of this surgical step.

The neglected cranial nerve: nervus terminalis (cranial nerve N).

PubMed

Vilensky, Joel A

2014-01-01

The nervus terminalis (NT; terminal nerve) was clearly identified as an additional cranial nerve in humans more than a century ago yet remains mostly undescribed in modern anatomy textbooks. The nerve is referred to as the nervus terminalis because in species initially examined its fibers were seen entering the brain in the region of the lamina terminalis. It has also been referred to as cranial nerve 0, but because there is no Roman symbol for zero, an N for the Latin word nulla is a better numerical designation. This nerve is very distinct in human fetuses and infants but also has been repeatedly identified in adult human brains. The NT fibers are unmyelinated and emanate from ganglia. The fibers pass through the cribriform plate medial to those of the olfactory nerve fila. The fibers end in the nasal mucosa and probably arise from autonomic/neuromodulatory as well as sensory neurons. The NT has been demonstrated to release luteinizing-releasing luteinizing hormone and is therefore thought to play a role in reproductive behavior. Based on the available evidence, the NT appears to be functional in adult humans and should be taught in medical schools and incorporated into anatomy/neuroanatomy textbooks. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

Detection of a diabetic sural nerve from the magnetic field after electric stimulation

NASA Astrophysics Data System (ADS)

Hayami, Takehito; Iramina, Keiji; Hyodo, Akira; Chen, Xian; Sunagawa, Kenji

2009-04-01

In this study, we proposed a new diagnostic technique for diabetic neuropathy using biomagnetic measurement. Peripheral neuropathy is one of the most common complications of diabetes. To examine the injury, the skin potential around the nerve is often measured after electric stimulation. However, measuring the magnetic field may reveal precise condition of the injury. To evaluate the effect of measuring the magnetic field, a simulation study was performed. A diabetic sural nerve was simulated as a bundle of myelinated nerve fibers. Each fiber was modeled as an electric cable of Ranvier's nodes. Anatomical data were used to determine the number of nerve fibers and distribution of nerve fiber diameters. The electric potential and the magnetic field on the skin after electric stimulation were computed to the boundary element method. Biphasic time courses were obtained as the electric potential and the magnetic flux density at measurement points. In diabetic nerves, the longer interpeak latency of the electric potential wave and the shorter interpeak latency of the magnetic flux wave were obtained. Measuring both the electric potential and the magnetic flux density seemed to provide a noninvasive and objective marker for diabetic neuropathy.

What is the Best Strategy on Detection of Cornea Neuropathy in People with Diabetes? Recent Advances in Potential Measurements.

PubMed

Lv, Ying; Zhao, Shaozhen

2018-03-26

There are well-acknowledged clinical or pre-clinical measurements concerning diabetic peripheral neuropathy(DPN). The current gold standard for diagnosis of diabetic peripheral neuropathy is nerve conduction suitable for detecting large nerve fiber function[1] and intraepidermal nerve fiber density assessment for small fiber damage evaluation[2]. The lack of a sensitive, non-invasive, and repeatable endpoint to measure changes in small nerve fibers is a major factor holding back clinical trials for the treatment of diabetic peripheral neuropathy. As cornea is the most densely innerved tissue, assessing corneal nerves' structure and function will be promising to predict and assess the degree of DPN [3]. In the diabetic micro-environment, damaged corneal nerves lead to decreased corneal sensitivity, both of which resulting in abnormal tear function. According to this theory, the measurements of nerve structure, corneal sensitivity, tear secretion and tear components, to some extent, can reveal and assess the state of corneal neuropathy. This review focuses on summarizing the knowledge of the latest detective methods of diabetic corneal neuropathy, popular in use or possible to further in study and be applied into clinical practice. Copyright © 2018 Elsevier B.V. All rights reserved.

Development of the intrinsic and extrinsic innervation of the gut.

PubMed

Uesaka, Toshihiro; Young, Heather M; Pachnis, Vassilis; Enomoto, Hideki

2016-09-15

The gastrointestinal (GI) tract is innervated by intrinsic enteric neurons and by extrinsic efferent and afferent nerves. The enteric (intrinsic) nervous system (ENS) in most regions of the gut consists of two main ganglionated layers; myenteric and submucosal ganglia, containing numerous types of enteric neurons and glial cells. Axons arising from the ENS and from extrinsic neurons innervate most layers of the gut wall and regulate many gut functions. The majority of ENS cells are derived from vagal neural crest cells (NCCs), which proliferate, colonize the entire gut, and first populate the myenteric region. After gut colonization by vagal NCCs, the extrinsic nerve fibers reach the GI tract, and Schwann cell precursors (SCPs) enter the gut along the extrinsic nerves. Furthermore, a subpopulation of cells in myenteric ganglia undergoes a radial (inward) migration to form the submucosal plexus, and the intrinsic and extrinsic innervation to the mucosal region develops. Here, we focus on recent progress in understanding the developmental processes that occur after the gut is colonized by vagal ENS precursors, and provide an up-to-date overview of molecular mechanisms regulating the development of the intrinsic and extrinsic innervation of the GI tract. Copyright © 2016 Elsevier Inc. All rights reserved.

FIBER-OPTIC BIOSENSOR FOR DIRECT DETERMINATION OF ORGANOPHOSPHATE NERVE AGENTS. (R823663)

EPA Science Inventory

A fiber-optic enzyme biosensor for the direct measurement of organophosphate nerve
agents was developed. The basic element of this biosensor is organophosphorus hydrolase
immobilized on a nylon membrane and attached to the common end of a bifurcated optical fiber
bundle....

PATHOLOGICAL SPROUTING OF ADULT NOCICEPTORS IN CHRONIC PROSTATE CANCER-INDUCED BONE PAIN

PubMed Central

Jimenez-Andrade, Juan M.; Bloom, Aaron P.; Stake, James I.; Mantyh, William G.; Taylor, Reid N.; Freeman, Katie T.; Ghilardi, Joseph R.; Kuskowski, Michael A.; Mantyh, Patrick W.

2012-01-01

Pain frequently accompanies cancer. What remains unclear is why this pain frequently becomes more severe and difficult to control with disease progression. Here we test the hypothesis that with disease progression, sensory nerve fibers that innervate the tumor-bearing tissue undergo a pathological sprouting and reorganization, which in other non-malignant pathologies has been shown to generate and maintain chronic pain. Injection of canine prostate cancer cells into mouse bone induces a remarkable sprouting of calcitonin gene related peptide (CGRP+) and neurofilament 200 kDa (NF200+) sensory nerve fibers. Nearly all sensory nerve fibers that undergo sprouting also co-express tropomyosin receptor kinase A (TrkA+). This ectopic sprouting occurs in sensory nerve fibers that are in close proximity to colonies of prostate cancer cells, tumor-associated stromal cells and newly formed woven bone, which together form sclerotic lesions that closely mirror the osteoblastic bone lesions induced by metastatic prostate tumors in humans. Preventive treatment with an antibody that sequesters nerve growth factor (NGF), administered when the pain and bone remodeling were first observed, blocks this ectopic sprouting and attenuates cancer pain. Interestingly, RT-PCR analysis indicated that the prostate cancer cells themselves do not express detectable levels of mRNA coding for NGF. This suggests that the tumor-associated stromal cells express and release NGF, which drives the pathological reorganization of nearby TrkA+ sensory nerve fibers. Therapies that prevent this reorganization of sensory nerve fibers may provide insight into the evolving mechanisms that drive cancer pain and lead to more effective control of this chronic pain state. PMID:21048122

Innervation pattern of polycystic ovaries in the women.

PubMed

Wojtkiewicz, Joanna; Jana, Barbara; Kozłowska, Anna; Crayton, Robert; Majewski, Mariusz; Zalecki, Michał; Baranowski, Włodzimierz; Radziszewski, Piotr

2014-11-01

The aim of the present study was to determine the changes in both the distribution pattern and density of nerve fibers containing dopamine β-hydroxylase (DβH), vesicular acetylcholine transporter (VAChT), neuronal nitric oxide synthase (nNOS), substance P (SP), calcitonin gene related peptide (CGRP), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), somatostatin (SOM), galanin (GAL) and pituitary adenylate cyclase-activating polypeptide (PACAP) in the human polycystic ovaries. In the polycystic ovaries, when compared to the immunoreactions pattern observed in the control gonads, following changes were revealed: (1) an increase in the number of DβH-, VAChT-, VIP- or GAL-immunoreactive (IR) nerve fibers within the stroma as well as in the number of DβH-IR fibers near primordial follicles and medullar veins and venules; (2) a reduction in the number of nerve fibers containing nNOS, CGRP, SOM, PACAP within the stroma and in the numbers of CGRP-IR fibers around arteries; (3) an appearance of SP- and GAL-IR fibers around medullar and cortical arteries, arterioles, veins and venules, with except of GAL-IR fibers supplying medullar veins; and (4) the lack of nNOS-IR nerve fibers near primordial follicles and VIP-IR nerves around medullar arteries and arterioles. In conclusion, our results suggest that the changes in the innervation pattern of the polycystic ovaries in human may play an important role in the pathogenesis and/or course of this disorder. Copyright © 2014. Published by Elsevier B.V.

Molecular characteristics suggest an effector function of palisade endings in extraocular muscles.

PubMed

Konakci, Kadriye Zeynep; Streicher, Johannes; Hoetzenecker, Wolfram; Blumer, Michael Josef Franz; Lukas, Julius-Robert; Blumer, Roland

2005-01-01

To analyze palisade endings in cat extraocular muscles (EOMs) and to clarify whether these EOM-specific organs are sensory or motor. Twelve cats aged between 1 and 16 years were analyzed. Whole EOM tendons were immunostained using four different combinations of triple fluorescence labeling. Triple labeling included antibodies against choline acetyltransferase (ChAT), neurofilament, synaptophysin, and alpha-bungarotoxin. Preparations were examined by confocal laser scanning microscopy. ChAT-labeled EOMs were also analyzed by immunoelectron microscopy. Three-dimensional reconstructions were made of palisade endings. Palisade endings were found in the distal and proximal myotendinous regions of cat EOMs. These endings arose from thin nerve fibers coming from the muscle and extending into the tendon. There, the nerve fibers turned back 180 degrees to divide into terminal branches around the muscle fiber tips. Terminal branches established numerous contacts with the tendon attached to the muscle fiber tip and only a few contacts with the muscle fiber. Often, nerve fibers forming palisade endings on muscle fiber tips were observed to establish multiple motor contacts on muscle fibers outside palisade endings. Three-dimensional reconstructions depicted the complex morphology of the palisade endings. All nerve fibers supplying palisade endings stained positively for ChAT and neurofilament. All nerve terminals in palisade endings were ChAT and synaptophysin positive. Only neuromuscular contacts in palisade endings were positive for alpha-bungarotoxin, as well. This study provides evidence that palisade endings in cat EOMs have effector function. The findings may be of significance for strabismus surgery because palisade endings are also found in human EOMs.

The Functional Anatomy of Nerves Innervating the Ventral Grooved Blubber of Fin Whales (Balaenoptera Physalus).

PubMed

Vogl, Wayne; Petersen, Hannes; Adams, Arlo; Lillie, Margo A; Shadwick, Robert E

2017-11-01

Nerves that supply the floor of the oral cavity in rorqual whales are extensible to accommodate the dramatic changes in tissue dimensions that occur during "lunge feeding" in this group. We report here that the large nerves innervating the muscle component of the ventral grooved blubber (VGB) in fin whales are branches of cranial nerve VII (facial nerve). Therefore, the muscles of the VGB are homologous to second branchial arch derived muscles, which in humans include the muscles of "facial expression." We speculate, based on the presence of numerous foramina on the dorsolateral surface of the mandibular bones, that general sensation from the VGB likely is carried by branches of the mandibular division (V3) of cranial nerve V (trigeminal nerve), and that these small branches travel in the lipid-rich layer directly underlying the skin. We show that intercostal and phrenic nerves, which are not extensible, have a different wall and nerve core morphology than the large VGB nerves that are branches of VII. Although these VGB nerves are known to have two levels of waviness, the intercostal and phrenic nerves have only one in which the nerve fascicles in the nerve core are moderately wavy. In addition, the VGB nerves have inner and outer parts to their walls with numerous large elastin fibers in the outer part, whereas intercostal and phrenic nerves have single walls formed predominantly of collagen. Our results illustrate that overall nerve morphology depends greatly on location and the forces to which the structures are exposed. Anat Rec, 300:1963-1972, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Combining retinal nerve fiber layer thickness with individual retinal blood vessel locations allows modeling of central vision loss in glaucoma

NASA Astrophysics Data System (ADS)

Wang, Hui; Wang, Mengyu; Baniasadi, Neda; Jin, Qingying; Elze, Tobias

2017-02-01

Purpose: To assess whether modeling of central vision loss (CVL) due to glaucoma by optical coherence tomography (OCT) retinal nerve fiber (RNF) layer thickness (RNFLT) can be improved by including the location of the major inferior temporal retinal artery (ITA), a known correlate of individual RNF geometry. Methods: Pat- tern deviations of the two locations of the Humphrey 24-2 visual field (VF) known to be specifically vulnerable to glaucomatous CVL and OCT RNFLT on the corresponding circumpapillary sector around the optic nerve head within the radius of 1.73mm were retrospectively selected from 428 eyes of 428 patients of a large clinical glaucoma service. ITA was marked on the 1.73mm circle by a trained observer. Linear regression models were fitted with CVL as dependent variable and VF mean deviation (MD) plus either of (1) RNFLT, (2) ITA, and (3) their combination, respectively, as regressors. To assess CVL over all levels of glaucoma severity, the three models were compared to a null model containing only MD. A Baysian model comparison was performed with the Bayes Factor (BF) as measure of strength of evidence (BF<3: no evidence, 3-20: positive evidence, >20: strong evidence over null model). Results: Neither RNFLT (BF=0.9) nor ITA (BF=1.4) alone provided positive evidence over the null model, but their combination resulted in a model with strong evidence (BF=21.4). Conclusion: While the established circumpapillary RNFLT sector, based on population statistics, could not satisfactorily model CVL, the inclusion of a retinal parameter related to individual eye anatomy yielded a strong structure-function model.

Optical Coherence Tomography Scan Circle Location and Mean Retinal Nerve Fiber Layer Measurement Variability

PubMed Central

Gabriele, Michelle L.; Ishikawa, Hiroshi; Wollstein, Gadi; Bilonick, Richard A.; Townsend, Kelly A.; Kagemann, Larry; Wojtkowski, Maciej; Srinivasan, Vivek J.; Fujimoto, James G.; Duker, Jay S.; Schuman, Joel S.

2009-01-01

PURPOSE To investigate the effect on optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness measurements of varying the standard 3.4-mm-diameter circle location. METHODS The optic nerve head (ONH) region of 17 eyes of 17 healthy subjects was imaged with high-speed, ultrahigh-resolution OCT (hsUHR-OCT; 501 × 180 axial scans covering a 6 × 6-mm area; scan time, 3.84 seconds) for a comprehensive sampling. This method allows for systematic simulation of the variable circle placement effect. RNFL thickness was measured on this three-dimensional dataset by using a custom-designed software program. RNFL thickness was resampled along a 3.4-mm-diameter circle centered on the ONH, then along 3.4-mm circles shifted horizontally (x-shift), vertically (y-shift) and diagonally up to ±500 µm (at 100-µm intervals). Linear mixed-effects models were used to determine RNFL thickness as a function of the scan circle shift. A model for the distance between the two thickest measurements along the RNFL thickness circular profile (peak distance) was also calculated. RESULTS RNFL thickness tended to decrease with both positive and negative x- and y-shifts. The range of shifts that caused a decrease greater than the variability inherent to the commercial device was greater in both nasal and temporal quadrants than in the superior and inferior ones. The model for peak distance demonstrated that as the scan moves nasally, the RNFL peak distance increases, and as the circle moves temporally, the distance decreases. Vertical shifts had a minimal effect on peak distance. CONCLUSIONS The location of the OCT scan circle affects RNFL thickness measurements. Accurate registration of OCT scans is essential for measurement reproducibility and longitudinal examination (ClinicalTrials.gov number, NCT00286637). PMID:18515577

Does Optic Nerve Head Size Variation Affect Circumpapillary Retinal Nerve Fiber Layer Thickness Measurement by Optical Coherence Tomography?

PubMed Central

Huang, David; Chopra, Vikas; Lu, Ake Tzu-Hui; Tan, Ou; Francis, Brian; Varma, Rohit

2012-01-01

Purpose. To determine the relationship between retinal nerve fiber layer (RNFL) thickness, optic disc size, and image magnification. Methods. The cohort consisted of 196 normal eyes of 101 participants in the Advanced Imaging for Glaucoma Study (AIGS), a multicenter, prospective, longitudinal study to develop advanced imaging technologies for glaucoma diagnosis. Scanning laser tomography was used to measure disc size. Optical coherence tomography (OCT) was used to perform circumpapillary RNFL thickness measurements using the standard fixed 3.46-mm nominal scan diameter. A theoretical model of magnification effects was developed to relate RNFL thickness (overall average) with axial length and magnification. Results. Multivariate regression showed no significant correlation between RNFL thickness and optic disc area (95% confidence interval [CI] = −0.9 to 4.1 μm/mm2, P = 0.21). Linear regression showed that RNFL thickness depended significantly on axial length (slope = −3.1 μm/mm, 95% CI = −4.9 to −1.3, P = 0.001) and age (slope = −0.3 μm/y, 95% CI = −0.5 to −0.2, P = 0.0002). The slope values agreed closely with the values predicted by the magnification model. Conclusions. There is no significant association between RNFL thickness and optic disc area. Previous publications that showed such an association may have been biased by the effect of axial length on fundus image magnification and, therefore, both measured RNFL thickness and apparent disc area. The true diameter of the circumpapillary OCT scan is larger for a longer eye (more myopic eye), leading to a thinner RNFL measurement. Adjustment of measured RNFL thickness by axial length, in addition to age, may lead to a tighter normative range and improve the detection of RNFL thinning due to glaucoma. PMID:22743319

Retinal Nerve Fiber Layer Thickness Changes in the Pseudoexfoliation Syndrome: A Meta-Analysis of Case-Control Studies.

PubMed

Yu, Ji-Guo; Huang, Qing; Zhou, Xiao-Fang; Ding, Yi; Li, Jing; Xiang, Yi

2018-01-01

To evaluate and compare changes in retinal nerve fiber layer (RNFL) thickness in patients with the pseudoexfoliation syndrome (PXS) and healthy controls. Case-control studies were selected through an electronic search of the Cochrane Controlled Trials Register, PubMed, and Embase. Results were reviewed to ensure that the included studies met prespecified inclusion/exclusion criteria, and the quality of each study was assessed using the Newcastle-Ottawa Scale. All included studies measured average and 4-quadrant (temporal, superior, nasal, and inferior) RNFL thickness using optical coherence tomography (OCT). For the continuous outcomes, we calculated the weighted mean difference (WMD) and 95% confidence intervals (CIs). Eight case-control studies were included in this meta-analysis involving 225 eyes of PXS patients and 208 eyes of healthy controls in total. Statistical analysis revealed that the average RNFL thickness in PXS patients was significantly reduced compared to healthy controls (WMD = -6.91, 95% CI: -9.99 to -3.82, p < 0.0001). Additionally, differences in RNFL thickness in the superior quadrant (WMD = -10.68, 95% CI: -16.40 to -4.95, p = 0.0003), inferior quadrant (WMD = -8.20, 95% CI: -10.85 to -5.55, p < 0.00001), nasal quadrant (WMD = -3.05, 95% CI: -5.21 to -0.90, p = 0.005), and temporal quadrant (WMD = -6.39, 95% CI: -9.98 to -2.80, p = 0.0005) were all significant between the two groups. These results suggest that it is important to evaluate RNFL thickness and the optic nerve head through OCT in patients with PXS in order to determine early glaucomatous damage and start timely intervention prior to visual field loss. © 2017 S. Karger AG, Basel.

Comparative data on SD-OCT for the retinal nerve fiber layer and retinal macular thickness in a large cohort with Marfan syndrome.

PubMed

Xu, WanWan; Kurup, Sudhi P; Fawzi, Amani A; Durbin, Mary K; Maumenee, Irene H; Mets, Marilyn B

2017-01-01

To report the distribution of macular and optic nerve topography in the eyes of individuals with Marfan syndrome aged 8-56 years using spectral domain optical coherence tomography (SD-OCT). Thirty-three patients with Marfan syndrome underwent a full eye examination including slit-lamp biomicroscopy, indirect ophthalmoscopy, and axial length measurement; and SD-OCT measurements of the retinal nerve fiber layer (RNFL) and macular thickness. For patients between the ages of 8 and 12 years, the average RNFL thickness is 98 ± 9 μm, the vertical cup to disc (C:D) ratio is 0.50 ± 0.10, the central subfield thickness (CST) is 274 ± 38 μm, and the macular volume is 10.3 ± 0.6 mm 3 . For patients between the ages of 13 and 17 years, the average RNFL is 86 ± 16 μm, the vertical C:D ratio is 0.35 ± 0.20, the CST is 259 ± 15 μm, and the macular volume is 10.1 ± 0.5 mm 3 . For patients 18 years or older, the average RNFL is 89 ± 12 μm, the vertical C:D ratio is 0.46 ± 0.18, the CST is 262 ± 20 μm, and the macular volume is 10.2 ± 0.4 mm 3 . When the average RNFL data are compared to a normative, age-adjusted database, 6 of 33 (18%) were thinner than the 5% limit. This study reports the distribution of SD-OCT data for patients with Marfan syndrome. Compared to a normative database, 18% of eyes with Marfan syndrome had RNFL thickness < 5% of the population.

Comparison of diagnostic capability of macular ganglion cell complex and retinal nerve fiber layer among primary open angle glaucoma, ocular hypertension, and normal population using Fourier-domain optical coherence tomography and determining their functional correlation in Indian population

PubMed Central

Barua, Nabanita; Sitaraman, Chitra; Goel, Sonu; Chakraborti, Chandana; Mukherjee, Sonai; Parashar, Hemandra

2016-01-01

Context: Analysis of diagnostic ability of macular ganglionic cell complex and retinal nerve fiber layer (RNFL) in glaucoma. Aim: To correlate functional and structural parameters and comparing predictive value of each of the structural parameters using Fourier-domain (FD) optical coherence tomography (OCT) among primary open angle glaucoma (POAG) and ocular hypertension (OHT) versus normal population. Setting and Design: Single centric, cross-sectional study done in 234 eyes. Materials and Methods: Patients were enrolled in three groups: POAG, ocular hypertensive and normal (40 patients in each group). After comprehensive ophthalmological examination, patients underwent standard automated perimetry and FD-OCT scan in optic nerve head and ganglion cell mode. The relationship was assessed by correlating ganglion cell complex (GCC) parameters with mean deviation. Results were compared with RNFL parameters. Statistical Analysis: Data were analyzed with SPSS, analysis of variance, t-test, Pearson's coefficient, and receiver operating curve. Results: All parameters showed strong correlation with visual field (P < 0.001). Inferior GCC had highest area under curve (AUC) for detecting glaucoma (0.827) in POAG from normal population. However, the difference was not statistically significant (P > 0.5) when compared with other parameters. None of the parameters showed significant diagnostic capability to detect OHT from normal population. In diagnosing early glaucoma from OHT and normal population, only inferior GCC had statistically significant AUC value (0.715). Conclusion: In this study, GCC and RNFL parameters showed equal predictive capability in perimetric versus normal group. In early stage, inferior GCC was the best parameter. In OHT population, single day cross-sectional imaging was not valuable. PMID:27221682

White matter of the brain

MedlinePlus

White matter is found in the deeper tissues of the brain (subcortical). It contains nerve fibers (axons), which are ... or covering called myelin. Myelin gives the white matter its color. It also protects the nerve fibers ...

Integration of Optical Coherence Tomography Scan Patterns to Augment Clinical Data Suite

NASA Technical Reports Server (NTRS)

Mason, S.; Patel, N.; Van Baalen, M.; Tarver, W.; Otto, C.; Samuels, B.; Koslovsky, M.; Schaefer, C.; Taiym, W.; Wear, M.;

Adaptive optics scanning laser ophthalmoscopy in fundus imaging, a review and update.

PubMed

Zhang, Bing; Li, Ni; Kang, Jie; He, Yi; Chen, Xiao-Ming

2017-01-01

Adaptive optics scanning laser ophthalmoscopy (AO-SLO) has been a promising technique in funds imaging with growing popularity. This review firstly gives a brief history of adaptive optics (AO) and AO-SLO. Then it compares AO-SLO with conventional imaging methods (fundus fluorescein angiography, fundus autofluorescence, indocyanine green angiography and optical coherence tomography) and other AO techniques (adaptive optics flood-illumination ophthalmoscopy and adaptive optics optical coherence tomography). Furthermore, an update of current research situation in AO-SLO is made based on different fundus structures as photoreceptors (cones and rods), fundus vessels, retinal pigment epithelium layer, retinal nerve fiber layer, ganglion cell layer and lamina cribrosa. Finally, this review indicates possible research directions of AO-SLO in future.

Adaptive optics scanning laser ophthalmoscopy in fundus imaging, a review and update

PubMed Central

Zhang, Bing; Li, Ni; Kang, Jie; He, Yi; Chen, Xiao-Ming

2017-01-01

Adaptive optics scanning laser ophthalmoscopy (AO-SLO) has been a promising technique in funds imaging with growing popularity. This review firstly gives a brief history of adaptive optics (AO) and AO-SLO. Then it compares AO-SLO with conventional imaging methods (fundus fluorescein angiography, fundus autofluorescence, indocyanine green angiography and optical coherence tomography) and other AO techniques (adaptive optics flood-illumination ophthalmoscopy and adaptive optics optical coherence tomography). Furthermore, an update of current research situation in AO-SLO is made based on different fundus structures as photoreceptors (cones and rods), fundus vessels, retinal pigment epithelium layer, retinal nerve fiber layer, ganglion cell layer and lamina cribrosa. Finally, this review indicates possible research directions of AO-SLO in future. PMID:29181321

Retinal ganglion cell complex and peripapillary retinal nerve fiber layer thicknesses following carotid endarterectomy.

PubMed

Guclu, Orkut; Guclu, Hande; Huseyin, Serhat; Korkmaz, Selcuk; Yuksel, Volkan; Canbaz, Suat; Pelitli Gurlu, Vuslat

2018-06-23

To examine changes in retinal ganglion cell complex (GCC) and peripapillary retinal nerve fiber layer (RNFL) thicknesses by optical coherence tomography (OCT) in contralateral and ipsilatateral eyes of carotid artery stenosis (CAS) patients before and after carotid endarterectomy (CEA). Forty-two consecutive patients diagnosed with CAS (70-99% stenosis rate) who underwent CEA were included in this prospective cross-sectional study. The indication for CEA was based on the Asymptomatic Carotid Atherosclerosis Study. Doppler ultrasonography and computed tomography angiography were performed to calculate CAS. All the subjects underwent an ophthalmological examination, including best corrected visual acuity (BCVA), intraocular pressure (IOP) measurements, biomicroscopy, fundoscopy, and OCT before and after the surgery. The mean preoperative intraocular pressure was 15.2 ± 2.1 mmHg in the ipsilateral eye and 15.8 ± 2.7 in the contralateral eye. The mean postoperative intraocular pressure in the ipsilateral and contralateral eye was 18.6 ± 3.0 and 19.3 ± 3.8, respectively. The intraocular pressure was significantly higher in postoperative eyes (p = 0.0001). There was a statistically significant decrease in peripapillary RNFL thickness in superior quadrants postoperatively in ipsilateral eyes. The retinal GCC layer thickness was not significantly different before and after CEA in ipsilateral and contralateral eyes. Carotid endarterectomy results in thinning of the superior peripapillary RNFL thickness. To the best of our knowledge, this is the first study to examine peripapillary RNFL and GCC thicknesses before and after CEA.

Thickness related textural properties of retinal nerve fiber layer in color fundus images.

PubMed

Odstrcilik, Jan; Kolar, Radim; Tornow, Ralf-Peter; Jan, Jiri; Budai, Attila; Mayer, Markus; Vodakova, Martina; Laemmer, Robert; Lamos, Martin; Kuna, Zdenek; Gazarek, Jiri; Kubena, Tomas; Cernosek, Pavel; Ronzhina, Marina

2014-09-01

Images of ocular fundus are routinely utilized in ophthalmology. Since an examination using fundus camera is relatively fast and cheap procedure, it can be used as a proper diagnostic tool for screening of retinal diseases such as the glaucoma. One of the glaucoma symptoms is progressive atrophy of the retinal nerve fiber layer (RNFL) resulting in variations of the RNFL thickness. Here, we introduce a novel approach to capture these variations using computer-aided analysis of the RNFL textural appearance in standard and easily available color fundus images. The proposed method uses the features based on Gaussian Markov random fields and local binary patterns, together with various regression models for prediction of the RNFL thickness. The approach allows description of the changes in RNFL texture, directly reflecting variations in the RNFL thickness. Evaluation of the method is carried out on 16 normal ("healthy") and 8 glaucomatous eyes. We achieved significant correlation (normals: ρ=0.72±0.14; p≪0.05, glaucomatous: ρ=0.58±0.10; p≪0.05) between values of the model predicted output and the RNFL thickness measured by optical coherence tomography, which is currently regarded as a standard glaucoma assessment device. The evaluation thus revealed good applicability of the proposed approach to measure possible RNFL thinning. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Structure-Function Correlation Using Confocal Laser Ophthalmoscope in Primary Open-Angle Glaucoma and Pseudoexfoliative Glaucoma.

PubMed

Pappas, Theofanis; Founti, Panayiota; Yin, Xiang Jun; Koskosas, Archimidis; Anastasopoulos, Eleftherios; Salonikiou, Angeliki; Kilintzis, Vasilios; Antoniadis, Antonios; Ziakas, Nikolaos; Topouzis, Fotis

2016-04-01

To compare Heidelberg Retina Tomograph (HRT) optic disc parameters and structure-function correlation between primary open-angle glaucoma (POAG) and pseudoexfoliative glaucoma (PEXG). Prospective, observation case series. A total of 54 POAG and 33 PEXG cases, consecutively recruited from a University Glaucoma Service, underwent a comprehensive ophthalmic examination, including HRT optic disc imaging. Glaucoma definition required the presence of both structural and functional damage. One eye per subject was included in the analysis. T test, Mann-Whitney U test, and analysis of covariance were used to compare HRT parameters between POAG and PEXG, adjusting for age, mean deviation (MD) in the visual field, intraocular pressure, and disc area. The correlation between HRT and MD was assessed in each group. Cup area (P=0.048), height variation contour (P=0.016), and cup/disc area ratio (P=0.023) were higher in POAG, whereas the mean retinal nerve fiber layer thickness (P=0.048), retinal nerve fiber layer cross-section area (P=0.044), and rim area (P=0.048) were lower in POAG, compared with PEXG. The correlation of HRT parameters with MD was significant only in the POAG group. At a similar level of functional damage, POAG subjects presented with more pronounced structural damage than PEXG subjects. The correlation between HRT and visual field parameters was more evident in POAG, compared with PEXG.

Changes in Retinal Nerve Fiber Layer Thickness after Multiple Injections of Novel VEGF Decoy Receptor Conbercept for Various Retinal Diseases.

PubMed

Zhang, Zhihua; Yang, Xiaolu; Jin, Huiyi; Qu, Yuan; Zhang, Yuan; Liu, Kun; Xu, Xun

2016-12-06

Conbercept is a recombinant fusion protein with high affinity for all vascular endothelial growth factor isoforms and placental growth factor. The repeated intravitreal injection of conbercept may cause intraocular pressure (IOP) fluctuations and long-term suppression of neurotrophic cytokines, which could lead to retinal nerve fiber layer (RNFL) damage. This retrospective fellow-eye controlled study included 98 eyes of 49 patients. The changes in IOP and RNFL thickness as well as the correlation between RNFL changes and associated factors were evaluated. The IOP value between the baseline and the last follow-up visit in the injection group and the IOP value of the last follow-up visit between the injection and non-injection groups were not significantly different (p = 0.452 and 0.476, respectively). The global average thickness of the RNFL (μm) in the injection group decreased from 108.9 to 106.1; however, the change was not statistically significant (p = 0.118). No significant difference in the average RNFL thickness was observed at the last follow-up visit between the injection and non-injection groups (p = 0.821). The type of disease was the only factor associated with RNFL thickness changes. In conclusion, repeated intravitreal injections with 0.05 mL conbercept revealed an excellent safety profile for RNFL thickness, although short-term IOP changes were observed.

The association of Helicobacter pylori with choroidal and retinal nerve fiber layer thickness.

PubMed

Can, Mehmet Erol; Kaplan, Fatma Efe; Uzel, Mehmet Murat; Kiziltoprak, Hasan; Ergun, Mustafa Cagri; Koc, Mustafa; Simsek, Gülcin

2017-08-05

To investigate the effect of Helicobacter pylori (H. pylori) infection on choroidal thickness (CT) and retinal nerve fiber layer thickness (RNFLT). The study included 25 patients with H. pylori infection and 25 healthy individuals as the control group. Helicobacter pylori patients were classified as the pre-treatment (Group 1; n: 25) and the post-treatment (Group 2; n: 25). RNFLT and CT were measured before and after treatment of H. pylori infection, using enhanced depth imaging (EDI) spectral-domain optical coherence tomography (Spectralis, Heidelberg Engineering, Heidelberg, Germany). The axial length and intraocular pressure were also measured. The mean subfoveal CT was 320.96 ± 29.15 μm in Group 1 and 287.48 ± 49.17 in the control group (p = 0.007), while the mean subfoveal CT did not show any difference between Group 2 and the control group (p > 0.05). No statistically significant difference was determined between the H. pylori patients and the control group in respect of RNFLT values (p > 0.05). CT increases during H. pylori infection and returns to the normal range within 6 weeks of treatment. RNFLT does not show any change during H. pylori infection. The data related to the subfoveal CT may be useful in understanding the pathogenesis of central serous chorioretinopathy developing in H. pylori patients.

White centered retinal hemorrhages in vitamin b(12) deficiency anemia.

PubMed

Zehetner, Claus; Bechrakis, Nikolaos E

2011-05-01

To report a case of severe vitamin B(12) deficiency anemia presenting with white centered retinal hemorrhages. Interventional case report. A 40-year-old man, general practitioner himself, presented with a 1-day history of diminished left visual acuity and a drop-shaped central scotoma. The corrected visual acuities were 20/20, OD and 20/100, OS. Ophthalmic examination revealed bilaterally pale tarsal conjunctiva, discretely icteric bulbar conjunctiva and disseminated white centered intraretinal hemorrhages with foveal involvement. OCT imaging through these lesions revealed a retinal thickening caused by a sub-ILM accumulation of hyperreflective and inhomogeneous deposits within the nerve fiber layer. Immediate laboratory work-up showed severe megaloblastic anemia caused by vitamin B(12) deficiency requiring erythrocyte transfusions. Most reports of white centered retinal hemorrhages have been described in patients with leukemic retinopathy and bacterial endocarditis. It is interesting that this case of vitamin B(12) deficiency anemia retinopathy has a clinically indistinguishable fundus appearance. This is probably due to the common pathology of capillary disruption and subsequent hemostatic fibrin plug formation. In megaloblastic anemia, direct anoxia results in endothelial dysfunction. The loss of impermeability allows extrusion of whole blood and subsequent diffusion from the disrupted site throughout and above the nerve fiber layer. Therefore the biomicroscopic pattern of white centered hemorrhages observed in anemic retinopathy is most likely due to the clot formation as the reparative sequence after capillary rupture.

Detection of retinal nerve fiber layer defects in retinal fundus images using Gabor filtering

NASA Astrophysics Data System (ADS)

Hayashi, Yoshinori; Nakagawa, Toshiaki; Hatanaka, Yuji; Aoyama, Akira; Kakogawa, Masakatsu; Hara, Takeshi; Fujita, Hiroshi; Yamamoto, Tetsuya

2007-03-01

Retinal nerve fiber layer defect (NFLD) is one of the most important findings for the diagnosis of glaucoma reported by ophthalmologists. However, such changes could be overlooked, especially in mass screenings, because ophthalmologists have limited time to search for a number of different changes for the diagnosis of various diseases such as diabetes, hypertension and glaucoma. Therefore, the use of a computer-aided detection (CAD) system can improve the results of diagnosis. In this work, a technique for the detection of NFLDs in retinal fundus images is proposed. In the preprocessing step, blood vessels are "erased" from the original retinal fundus image by using morphological filtering. The preprocessed image is then transformed into a rectangular array. NFLD regions are observed as vertical dark bands in the transformed image. Gabor filtering is then applied to enhance the vertical dark bands. False positives (FPs) are reduced by a rule-based method which uses the information of the location and the width of each candidate region. The detected regions are back-transformed into the original configuration. In this preliminary study, 71% of NFLD regions are detected with average number of FPs of 3.2 per image. In conclusion, we have developed a technique for the detection of NFLDs in retinal fundus images. Promising results have been obtained in this initial study.

INTERNAL LIMITING MEMBRANE PEELING-DEPENDENT RETINAL STRUCTURAL CHANGES AFTER VITRECTOMY IN RHEGMATOGENOUS RETINAL DETACHMENT.

PubMed

Hisatomi, Toshio; Tachibana, Takashi; Notomi, Shoji; Koyanagi, Yoshito; Murakami, Yusuke; Takeda, Atsunobu; Ikeda, Yasuhiro; Yoshida, Shigeo; Enaida, Hiroshi; Murata, Toshinori; Sakamoto, Taiji; Sonoda, Koh-Hei; Ishibashi, Tatsuro

2018-03-01

To examine retinal changes after vitrectomy with internal limiting membrane (ILM) peeling, we used 3-dimensional optical coherence tomography (3D-OCT) in rhegmatogenous retinal detachment cases. The 68 eyes from 67 patients with rhegmatogenous retinal detachment were studied, including 35 detached macula cases (51%) and 33 attached macula cases. Internal limiting membrane peeling was performed with fine forceps after brilliant blue G staining. The 3D-OCT images were obtained with volume-rendering technologies from cross-sectional OCT images. The 3D-OCT detected 45 eyes (66%) with ILM peeling-dependent retinal changes, including dissociated optic nerve fiber layer appearance, dimple sign, temporal macular thinning, ILM peeling area thinning, or forceps-related retinal thinning. The ILM peeled area was detectable in only 9 eyes with 3D-OCT, whereas it was undetectable in other 59 eyes. The dissociated optic nerve fiber layer appearance was detected in 8 of the total cases (12%), and dimple signs were observed in 14 cases (21%). Forceps-related thinning was also noted in eight cases (24%) of attached macula cases and in four cases (11%) of detached macula cases. No postoperative macular pucker was noted in the observational period. The 3D-OCT clearly revealed spatial and time-dependent retinal changes after ILM peeling. The changes occurred in 2 months and remained thereafter.

Changes in optical coherence tomography measurements after orbital wall decompression in dysthyroid optic neuropathy.

PubMed

Park, Kyung-Ah; Kim, Yoon-Duck; Woo, Kyung In

2018-06-01

The purpose of our study was to assess changes in peripapillary retinal nerve fiber layer (RNFL) thickness after orbital wall decompression in eyes with dysthyroid optic neuropathy (DON). We analyzed peripapillary optical coherence tomography (OCT) images (Cirrus HD-OCT) from controls and patients with DON before and 1 and 6 months after orbital wall decompression. There was no significant difference in mean preoperative peripapillary retinal nerve fiber layer thickness between eyes with DON and controls. The superior and inferior peripapillary RNFL thickness decreased significantly 1 month after decompression surgery compared to preoperative values (p = 0.043 and p = 0.022, respectively). The global average, superior, temporal, and inferior peripapillary RNFL thickness decreased significantly 6 months after decompression surgery compared to preoperative values (p = 0.015, p = 0.028, p = 0.009, and p = 0.006, respectively). Patients with greater preoperative inferior peripapillary RNFL thickness tended to have better postoperative visual acuity at the last visit (p = 0.024, OR = 0.926). Our data revealed a significant decrease in peripapillary RNFL thickness postoperatively after orbital decompression surgery in patients with DON. We also found that greater preoperative inferior peripapillary RNFL thickness was associated with better visual outcomes. We suggest that RNFL thickness can be used as a prognostic factor for DON before decompression surgery.

Retinal nerve fiber layer and macular thinning in systemic lupus erythematosus: an optical coherence tomography study comparing SLE and neuropsychiatric SLE.

PubMed

Liu, G Y; Utset, T O; Bernard, J T

2015-10-01

Due to the lack of reliable biomarkers in diagnosing and monitoring neuropsychiatric systemic lupus erythematosus (NPSLE), the aim of this study was to examine the utility of measurements obtained through spectral domain optical coherence tomography (SD-OCT) as a biomarker for NP involvement in SLE. Retinal nerve fiber layer (RNFL) and macula scans were performed using SD-OCT on 15 NPSLE patients, 16 SLE patients without NP symptoms (non-NP SLE), and 16 healthy controls. Macular volume and thickness of the central macula and peripapillary RNFL were compared between the groups and to scores on two validated cognitive tests. NPSLE patients did not differ significantly from non-NP SLE patients in retinal thickness or macular volume. However, SLE patients as a whole showed significant RNFL and macular thinning compared to controls. Scores on the Trail Making Test B, a test of complex attention, showed significant correlation to temporal superior and temporal inferior RNFL thickness. Our results demonstrate RNFL thinning in SLE, and confirm the previous finding of high incidence of abnormal brain scans in SLE. These findings suggest that OCT measurements may be indicative of neurodegeneration in SLE and may be a useful biomarker for early cognitive impairment in SLE. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Association of ABO blood groups and Rh factor with retinal and choroidal thickness.

PubMed

Teberik, Kuddusi; Eski, Mehmet Tahir

2018-06-01

To evaluate if ABO blood group and Rh factor have an effect on retinal and choroidal thickness. This study was designed prospectively. Retinal nerve fiber layer, retinal, and choroidal thicknesses were measured with spectral-domain optical coherence tomography. Retinal and choroidal thickness measurements (one subfoveal, three temporal, and three nasal) were obtained at 500-μm intervals up to 1500 μm with the caliper system. In this study, 109 male and 151 female, 260 individuals in total were included. There were 125 subjects in group A, 29 in group B, 34 in group AB, and 72 in group O. Rh factor was positive in 194 subjects and negative in 66. There was no significant difference between the groups regarding age (p = 0.667). The groups did not show any statistical difference in retinal nerve fiber layer thickness. There was significant difference found for mean retinal thickness at temporal 1000 μm when four groups were compared (p = 0.037). No statistically significant difference was detected for the remaining retinal and choroidal sectoral regions. The groups did not statistically significantly differ concerning Rh factor (p > 0.05). Although we found a significant difference in retinal thickness in the temporal retina between group B with group A and group O, we suggest that both blood group and Rh factor have no effect on retinal and choroidal thickness.

Na,K-ATPase alpha isoforms at the blood-cerebrospinal fluid-trigeminal nerve and blood-retina interfaces in the rat.

PubMed

Arakaki, Xianghong; McCleary, Paige; Techy, Matthew; Chiang, Jiarong; Kuo, Linus; Fonteh, Alfred N; Armstrong, Brian; Levy, Dan; Harrington, Michael G

2013-03-14

Cerebrospinal fluid (CSF) sodium concentration increases during migraine attacks, and both CSF and vitreous humor sodium increase in the rat migraine model. The Na,K-ATPase is a probable source of these sodium fluxes. Since Na,K-ATPase isoforms have different locations and physiological roles, our objective was to establish which alpha isoforms are present at sites where sodium homeostasis is disrupted. Specific Na,K-ATPase alpha isoforms were identified in rat tissues by immunohistochemistry at the blood-CSF barrier at the choroid plexus, at the blood-CSF-trigeminal barrier at the meninges, at the blood-retina barrier, and at the blood-aqueous barrier at the ciliary body. Calcitonin gene-related peptide (CGRP), occludin, or von Willibrand factor (vWF) were co-localized with Na,K-ATPase to identify trigeminal nociceptor fibers, tight junctions, and capillary endothelial cells respectively. The Na,K-ATPase alpha-2 isoform is located on capillaries and intensely at nociceptive trigeminal nerve fibers at the meningeal blood-CSF-trigeminal barrier. Alpha-1 and -3 are lightly expressed on the trigeminal nerve fibers but not at capillaries. Alpha-2 is expressed at the blood-retina barriers and, with alpha-1, at the ciliary body blood aqueous barrier. Intense apical membrane alpha-1 was associated with moderate cytoplasmic alpha-2 expression at the choroid plexus blood-CSF barrier. Na,K-ATPase alpha isoforms are present at the meningeal, choroid plexus, and retinal barriers. Alpha-2 predominates at the capillary endothelial cells in the meninges and retinal ganglion cell layer.

Na,K-ATPase alpha isoforms at the blood-cerebrospinal fluid-trigeminal nerve and blood-retina interfaces in the rat

PubMed Central

2013-01-01

Background Cerebrospinal fluid (CSF) sodium concentration increases during migraine attacks, and both CSF and vitreous humor sodium increase in the rat migraine model. The Na,K-ATPase is a probable source of these sodium fluxes. Since Na,K-ATPase isoforms have different locations and physiological roles, our objective was to establish which alpha isoforms are present at sites where sodium homeostasis is disrupted. Methods Specific Na,K-ATPase alpha isoforms were identified in rat tissues by immunohistochemistry at the blood-CSF barrier at the choroid plexus, at the blood-CSF-trigeminal barrier at the meninges, at the blood-retina barrier, and at the blood-aqueous barrier at the ciliary body. Calcitonin gene-related peptide (CGRP), occludin, or von Willibrand factor (vWF) were co-localized with Na,K-ATPase to identify trigeminal nociceptor fibers, tight junctions, and capillary endothelial cells respectively. Results The Na,K-ATPase alpha-2 isoform is located on capillaries and intensely at nociceptive trigeminal nerve fibers at the meningeal blood-CSF-trigeminal barrier. Alpha-1 and −3 are lightly expressed on the trigeminal nerve fibers but not at capillaries. Alpha-2 is expressed at the blood-retina barriers and, with alpha-1, at the ciliary body blood aqueous barrier. Intense apical membrane alpha-1 was associated with moderate cytoplasmic alpha-2 expression at the choroid plexus blood-CSF barrier. Conclusion Na,K-ATPase alpha isoforms are present at the meningeal, choroid plexus, and retinal barriers. Alpha-2 predominates at the capillary endothelial cells in the meninges and retinal ganglion cell layer. PMID:23497725

Development of active and sensitive material systems based on composites

NASA Astrophysics Data System (ADS)

Asanuma, Hiroshi

2002-07-01

This paper describes new concepts proposed by the author to realize active and sensitive structural material systems. Two examples of multifunctional composites were fabricated and evaluated in this study as follows: (1) An active laminate of aluminum plate (works as muscle), epoxy film (as insulator), unidirectional CFRP prepreg (as bone and blood vessel) and copper foil electrode (to apply voltage on CFRP) was made with an embedded optical fiber multiply fractured in the CFRP layer (works as nerve), of which curvature change could be effectively monitored with the fractured optical fiber. (2) A stainless steel fiber/aluminum active composite with embedded Ti oxide/Ti composite fiber was fabricated. The Ti oxide/Ti fiber could work as a sensor for temperature by removing a part of the oxide before embedment to make a metallic contact between the embedded titanium fiber and aluminum matrix to be able to generate thermal electromotive force, and also could work as a sensor for strain and as a heater for actuation. In the both cases, the outputs from their embedded sensors can be used to control their actuations.

Prevalence of myelinated retinal nerve fibres in adult Indians: the Central India Eye and Medical Study.

PubMed

Nangia, Vinay; Jonas, Jost B; Khare, Anshu; Bhate, Karishma; Agarwal, Shubhra; Panda-Jonas, Songhomitra

2014-05-01

To determine the prevalence of myelinated retinal nerve fibers in the adult Indian population. The Central India Eye and Medical Study performed in rural Central India included 4711 participants aged 30+ years. The participants underwent a detailed ophthalmic and medical examination. Readable fundus photographs were available for 8645 eyes of 4485 (95.2%) subjects. Myelinated retinal nerve fibers were detected in 52 eyes (46 subjects) with a prevalence rate of 0.58±0.08 per 100 eyes [95% confidence interval (CI): 0.42, 0.74] and 1.03±0.15 per 100 subjects (95%CI: 0.73, 1.32). Prevalence of myelinated retinal nerve fibers was significantly associated hyperopic refractive error (p=0.008; OR: 1.31; 95%CI: 1.07, 1.59). It was not significantly associated with age (p=0.11), best corrected visual acuity (logMAR; p=0.33), intraocular pressure (p=0.09), amount of nuclear cataract (p=0.93), optic disc area (p=0.60), presence of glaucomatous optic nerve atrophy (p=0.62), and early age-related macular degeneration (p=0.53). Myelinated retinal nerve fibers are present in about 10 out of 1000 adult Indians in rural Central India, with a higher prevalence in hyperopic eyes. Prevalence of myelinated retinal nerve fibers was not associated with age, visual acuity, glaucoma and macular degeneration. © 2013 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Feedback Information and Analysis for Microprocessor Controlled Muscle Stimulation.

DTIC Science & Technology

1981-12-01

muscle into fiberous tissue (Guyton, 1976) is not inevitable. The contractile power can be preserved and fiberous build-up reduced by electrical... isometric tension, velocity of contraction and coordination of movement, all with minimally induced muscle fatigue. The work of Petrofsky and Phillips... muscle . Each muscle fiber is innervated by only a single nerve, but a single motor nerve fiber branches to as many as thousands of different muscle

Neurotization of the phrenic nerve with accessory nerve for high cervical spinal cord injury with respiratory distress: an anatomic study.

PubMed

Wang, Ce; Zhang, Ying; Nicholas, Tsai; Wu, Guoxin; Shi, Sheng; Bo, Yin; Wang, Xinwei; Zhou, Xuhui; Yuan, Wen

2014-01-01

High cervical spinal cord injury is associated with high morbidity and mortality. Traditional treatments carry various complications such as infection, pacemaker failure and undesirable movement. Thus, a secure surgical strategy with fewer complications analogous to physiological ventilation is still required. We hope to offer one potential method to decrease the complications and improve survival qualities of patients from the aspect of anatomy. The purpose of the study is to provide anatomic details on the accessory nerve and phrenic nerve for neurotization in patients with high spinal cord injuries. 38 cadavers (76 accessory and 76 phrenic nerves) were dissected in the study. The width, length and thickness of each accessory nerve and phrenic nerve above clavicle were measured. The distances from several landmarks on accessory nerve to the origin and the end of the phrenic nerve above clavicle were measured too. Then, the number of motor nerve fibers on different sections of the nerves was calculated using the technique of immunohistochemistry. The accessory nerves distal to its sternocleidomastoid muscular branches were 1.52 ± 0.32 mm ~1.54 ± 0.29 mm in width, 0.52 ± 0.18 mm ~ 0.56 ± 0.20mm in thickness and 9.52 ± 0.98 cm in length. And the phrenic nerves above clavicle were 1.44 ± 0.23 mm ~ 1.45 ± 0.24 mm in width, 0.47 ± 0.15 mm ~ 0.56 ± 0.25 mm in thickness and 6.48 ± 0.78 cm in length. The distance between the starting point of accessory nerve and phrenic nerve were 3.24 ± 1.17 cm, and the distance between the starting point of accessory nerve and the end of the phrenic nerve above clavicle were 8.72 ± 0.84 cm. The numbers of motor nerve fibers in accessory nerve were 1,038 ± 320~1,102 ± 216, before giving out the sternocleidomastoid muscular branches. The number of motor nerve fibers in the phrenic nerve was 911 ± 321~1,338 ± 467. The accessory nerve and the phrenic were similar in width, thickness and the number of motor nerve fibers. And the lengths of accessory nerve were long enough for neuritisation with phrenic nerve.

Characterization of nerve and microvessel damage and recovery in type 1 diabetic mice after permanent femoral artery ligation.

PubMed

Lozeron, Pierre; Mantsounga, Chris S; Broqueres-You, Dong; Dohan, Anthony; Polivka, Marc; Deroide, Nicolas; Silvestre, Jean-Sébastien; Kubis, Nathalie; Lévy, Bernard I

2015-09-01

Neuropathy is the most common complication of the peripheral nervous system during the progression of diabetes. The pathophysiology is unclear but may involve microangiopathy, reduced endoneurial blood flow, and tissue ischemia. We used a mouse model of type 1 diabetes to study parallel alterations of nerves and microvessels following tissue ischemia. We designed an easily reproducible model of ischemic neuropathy induced by irreversible ligation of the femoral artery. We studied the evolution of behavioral function, epineurial and endoneurial vessel impairment, and large nerve myelinated fiber as well as small cutaneous unmyelinated fiber impairment for 1 month following the onset of ischemia. We observed a more severe hindlimb dysfunction and delayed recovery in diabetic animals. This was associated with reduced density of large arteries in the hindlimb and reduced sciatic nerve epineurial blood flow. A reduction in sciatic nerve endoneurial capillary density was also observed, associated with a reduction in small unmyelinated epidermal fiber number and large myelinated sciatic nerve fiber dysfunction. Moreover, vascular recovery was delayed, and nerve dysfunction was still present in diabetic animals at day 28. This easily reproducible model provides clear insight into the evolution over time of the impact of ischemia on nerve and microvessel homeostasis in the setting of diabetes. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Immunohistochemical localization of FMRFamide-containing neurons and nerve fibers in the ganglia and the gonad wall of the scallop, Pecten maximus (L).

PubMed

Henry, M; Benlinmame, N; Belhsen, O K; Jule, Y; Mathieu, M

1995-02-01

The Phe-Met-Arg-Phe NH2 (FMRFamide)-like immunoreactivity was detected in neurons of the cerebro-pedal and visceral ganglia of the scallop Pecten maximus using immunohistochemical techniques. FMRFamide-like immunoreactivity was also found in nerve fibers localized in the connective tissue and the epithelial wall of the gonad. Electron microscopy study carried out on the gonads indicates the existence of numerous nerve fibers crossing the connective tissue; nerve terminals apposed to highly secretory cells were seen in the gonad wall. All in all, the present immunohistochemical and electron microscopic data suggest that FMRFamide might play an unusual secretagogue role in the gonad wall.

Autologous transplantation with fewer fibers repairs large peripheral nerve defects

PubMed Central

Deng, Jiu-xu; Zhang, Dian-yin; Li, Ming; Weng, Jian; Kou, Yu-hui; Zhang, Pei-xun; Han, Na; Chen, Bo; Yin, Xiao-feng; Jiang, Bao-guo

2017-01-01

Peripheral nerve injury is a serious disease and its repair is challenging. A cable-style autologous graft is the gold standard for repairing long peripheral nerve defects; however, ensuring that the minimum number of transplanted nerve attains maximum therapeutic effect remains poorly understood. In this study, a rat model of common peroneal nerve defect was established by resecting a 10-mm long right common peroneal nerve. Rats receiving transplantation of the common peroneal nerve in situ were designated as the in situ graft group. Ipsilateral sural nerves (10–30 mm long) were resected to establish the one sural nerve graft group, two sural nerves cable-style nerve graft group and three sural nerves cable-style nerve graft group. Each bundle of the peroneal nerve was 10 mm long. To reduce the barrier effect due to invasion by surrounding tissue and connective-tissue overgrowth between neural stumps, small gap sleeve suture was used in both proximal and distal terminals to allow repair of the injured common peroneal nerve. At three months postoperatively, recovery of nerve function and morphology was observed using osmium tetroxide staining and functional detection. The results showed that the number of regenerated nerve fibers, common peroneal nerve function index, motor nerve conduction velocity, recovery of myodynamia, and wet weight ratios of tibialis anterior muscle were not significantly different among the one sural nerve graft group, two sural nerves cable-style nerve graft group, and three sural nerves cable-style nerve graft group. These data suggest that the repair effect achieved using one sural nerve graft with a lower number of nerve fibers is the same as that achieved using the two sural nerves cable-style nerve graft and three sural nerves cable-style nerve graft. This indicates that according to the ‘multiple amplification’ phenomenon, one small nerve graft can provide a good therapeutic effect for a large peripheral nerve defect. PMID:29323049

Spontaneous laryngeal reinnervation following chronic recurrent laryngeal nerve injury.

PubMed

Kupfer, Robbi A; Old, Matthew O; Oh, Sang Su; Feldman, Eva L; Hogikyan, Norman D

2013-09-01

To enhance understanding of spontaneous laryngeal muscle reinnervation following severe recurrent laryngeal nerve injury by testing the hypotheses that 1) nerve fibers responsible for thyroarytenoid muscle reinnervation can originate from multiple sources and 2) superior laryngeal nerve is a source of reinnervation. Prospective, controlled, animal model. A combination of retrograde neuronal labeling techniques, immunohistochemistry, electromyography, and sequential observations of vocal fold mobility were employed in rat model of chronic recurrent laryngeal nerve injury. The current study details an initial set of experiments in sham surgical and denervated group animals and a subsequent set of experiments in a denervated group. At 3 months after recurrent laryngeal nerve resection, retrograde brainstem neuronal labeling identified cells in the characteristic superior laryngeal nerve cell body location as well as cells in a novel caudal location. Regrowth of neuron fibers across the site of previous recurrent laryngeal nerve resection was seen in 87% of examined animals in the denervated group. Electromyographic data support innervation by both the superior and recurrent laryngeal nerves following chronic recurrent laryngeal nerve injury. Following chronic recurrent laryngeal nerve injury in the rat, laryngeal innervation is demonstrated through the superior laryngeal nerve from cells both within and outside of the normal cluster of cells that supply the superior laryngeal nerve. The recurrent laryngeal nerve regenerates across a surgically created gap, but functional significance of regenerated nerve fibers is unclear. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

Virtual tissue engineering and optic pathways: plotting the course of the axons in the retinal nerve fiber layer.

PubMed

Carreras, Francisco Javier; Medina, Javier; Ruiz-Lozano, Mariola; Carreras, Ignacio; Castro, Juan Luis

2014-04-17

As part of a larger project on virtual tissue engineering of the optic pathways, we describe the conditions that guide axons extending from the retina to the optic nerve head and formulate algorithms that meet such conditions. To find the entrance site on the optic nerve head of each axon, we challenge the fibers to comply with current models of axonal pathfinding. First, we build a retinal map using a single type of retinal ganglion cell (RGC) using density functions from the literature. Dendritic arbors are equated to receptive fields. Shape and size of retinal surface and optic nerve head (ONH) are defined. A computer model relates each soma to the corresponding entry point of its axon into the optic disc. Weights are given to the heuristics that guide the preference entry order in the nerve. Retinal ganglion cells from the area centralis saturate the temporal section of the disc. Retinal ganglion cells temporal to the area centralis curve their paths surrounding the fovea; some of these cells enter the disc centrally rather than peripherally. Nasal regions of the disc receive mixed axons from the far periphery of the temporal hemiretina, together with axons from the nasal half. The model plots the course of the axon using Bezier curves and compares them with clinical data, for a coincidence level of 86% or higher. Our model is able to simulate basic data of the early optic pathways including certain singularities and to mimic mechanisms operating during development, such as timing and fasciculation. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Auditory brainstem response latency in forward masking, a marker of sensory deficits in listeners with normal hearing thresholds

PubMed Central

Mehraei, Golbarg; Gallardo, Andreu Paredes; Shinn-Cunningham, Barbara G.; Dau, Torsten

2017-01-01

In rodent models, acoustic exposure too modest to elevate hearing thresholds can nonetheless cause auditory nerve fiber deafferentation, interfering with the coding of supra-threshold sound. Low-spontaneous rate nerve fibers, important for encoding acoustic information at supra-threshold levels and in noise, are more susceptible to degeneration than high-spontaneous rate fibers. The change in auditory brainstem response (ABR) wave-V latency with noise level has been shown to be associated with auditory nerve deafferentation. Here, we measured ABR in a forward masking paradigm and evaluated wave-V latency changes with increasing masker-to-probe intervals. In the same listeners, behavioral forward masking detection thresholds were measured. We hypothesized that 1) auditory nerve fiber deafferentation increases forward masking thresholds and increases wave-V latency and 2) a preferential loss of low-SR fibers results in a faster recovery of wave-V latency as the slow contribution of these fibers is reduced. Results showed that in young audiometrically normal listeners, a larger change in wave-V latency with increasing masker-to-probe interval was related to a greater effect of a preceding masker behaviorally. Further, the amount of wave-V latency change with masker-to-probe interval was positively correlated with the rate of change in forward masking detection thresholds. Although we cannot rule out central contributions, these findings are consistent with the hypothesis that auditory nerve fiber deafferentation occurs in humans and may predict how well individuals can hear in noisy environments. PMID:28159652

Histochemical discrimination of fibers in regenerating rat infraorbital nerve

NASA Technical Reports Server (NTRS)

Wilke, R. A.; Riley, D. A.; Sanger, J. R.

1992-01-01

In rat dorsal root ganglia, histochemical staining of carbonic anhydrase (CA) and cholinesterase (CE) yields a reciprocal pattern of activity: Sensory processes are CA positive and CE negative, whereas motor processes are CA negative and CE positive. In rat infraorbital nerve (a sensory peripheral nerve), we saw extensive CA staining of nearly 100% of the myelinated axons. Although CE reactivity in myelinated axons was extremely rare, we did observe CE staining of unmyelinated autonomic fibers. Four weeks after transection of infraorbital nerves, CA-stained longitudinal sections of the proximal stump demonstrated 3 distinct morphological zones. A fraction of the viable axons retained CA activity to within 2 mm of the distal extent of the stump, and the stain is capable of resolving growth sprouts being regenerated from these fibers. Staining of unmyelinated autonomic fibers in serial sections shows that CE activity was not retained as far distally as is the CA sensory staining.

Muscle fiber types composition and type identified endplate morphology of forepaw intrinsic muscles in the rat.

PubMed

Pan, Feng; Mi, Jing-Yi; Zhang, Yan; Pan, Xiao-Yun; Rui, Yong-Jun

2016-06-01

The failure to accept reinnervation is considered to be one of the reasons for the poor motor functional recovery of intrinsic hand muscles (IHMs) after nerve injury. Rat could be a suitable model to be used in simulating motor function recovery of the IHMs after nerve injury as to the similarities in function and anatomy of the muscles between human and rat. However, few studies have reported the muscle fiber types composition and endplate morphologic characteristics of intrinsic forepaw muscles (IFMs) in the rat. In this study, the myosin heavy chain isoforms and acetylcholine receptors were stained by immunofluorescence to show the muscle fiber types composition and endplates on type-identified fibers of the lumbrical muscles (LMs), interosseus muscles (IMs), abductor digiti minimi (AM) and flexor pollicis brevis (FM) in rat forepaw. The majority of IFMs fibers were labeled positively for fast-switch fiber. However, the IMs were composed of only slow-switch fiber. With the exception of the IMs, the other IFMs had a part of hybrid fibers. Two-dimensional morphological characteristics of endplates on I and IIa muscle fiber had no significant differences among the IFMs. The LMs is the most suitable IFMs of rat to stimulate reinnervation of the IHMs after nerve injury. Gaining greater insight into the muscle fiber types composition and endplate morphology in the IFMs of rat may help understand the pathological and functional changes of IFMs in rat model stimulating reinnervation of IHMs after peripheral nerve injury.

Retinal Ganglion Cell Damage in an Experimental Rodent Model of Blast-Mediated Traumatic Brain Injury

PubMed Central

Mohan, Kabhilan; Kecova, Helga; Hernandez-Merino, Elena; Kardon, Randy H.; Harper, Matthew M.

2013-01-01

Purpose. To evaluate retina and optic nerve damage following experimental blast injury. Methods. Healthy adult mice were exposed to an overpressure blast wave using a custom-built blast chamber. The effects of blast exposure on retina and optic nerve function and structure were evaluated using the pattern electroretinogram (pERG), spectral domain optical coherence tomography (OCT), and the chromatic pupil light reflex. Results. Assessment of the pupil response to light demonstrated decreased maximum pupil constriction diameter in blast-injured mice using red light or blue light stimuli 24 hours after injury compared with baseline in the eye exposed to direct blast injury. A decrease in the pupil light reflex was not observed chronically following blast exposure. We observed a biphasic pERG decrease with the acute injury recovering by 24 hours postblast and the chronic injury appearing at 4 months postblast injury. Furthermore, at 3 months following injury, a significant decrease in the retinal nerve fiber layer was observed using OCT compared with controls. Histologic analysis of the retina and optic nerve revealed punctate regions of reduced cellularity in the ganglion cell layer and damage to optic nerves. Additionally, a significant upregulation of proteins associated with oxidative stress was observed acutely following blast exposure compared with control mice. Conclusions. Our study demonstrates that decrements in retinal ganglion cell responses can be detected after blast injury using noninvasive functional and structural tests. These objective responses may serve as surrogate tests for higher CNS functions following traumatic brain injury that are difficult to quantify. PMID:23620426

Stem Cell Ophthalmology Treatment Study (SCOTS): bone marrow-derived stem cells in the treatment of Leber's hereditary optic neuropathy

PubMed Central

Weiss, Jeffrey N.; Levy, Steven; Benes, Susan C.

2016-01-01

The Stem Cell Ophthalmology Treatment Study (SCOTS) is currently the largest-scale stem cell ophthalmology trial registered at ClinicalTrials.gov (identifier: NCT01920867). SCOTS utilizes autologous bone marrow-derived stem cells (BMSCs) to treat optic nerve and retinal diseases. Treatment approaches include a combination of retrobulbar, subtenon, intravitreal, intra-optic nerve, subretinal, and intravenous injection of autologous BMSCs according to the nature of the disease, the degree of visual loss, and any risk factors related to the treatments. Patients with Leber's hereditary optic neuropathy had visual acuity gains on the Early Treatment Diabetic Retinopathy Study (ETDRS) of up to 35 letters and Snellen acuity improvements from hand motion to 20/200 and from counting fingers to 20/100. Visual field improvements were noted. Macular and optic nerve head nerve fiber layer typically thickened. No serious complications were seen. The increases in visual acuity obtained in our study were encouraging and suggest that the use of autologous BMSCs as provided in SCOTS for ophthalmologic mitochondrial diseases including Leber's hereditary optic neuropathy may be a viable treatment option. PMID:27904503

High Spatial Resolution Imaging Mass Spectrometry of Human Optic Nerve Lipids and Proteins

NASA Astrophysics Data System (ADS)

Anderson, David M. G.; Spraggins, Jeffrey M.; Rose, Kristie L.; Schey, Kevin L.

2015-06-01

The human optic nerve carries signals from the retina to the visual cortex of the brain. Each optic nerve is comprised of approximately one million nerve fibers that are organized into bundles of 800-1200 fibers surrounded by connective tissue and supportive glial cells. Damage to the optic nerve contributes to a number of blinding diseases including: glaucoma, neuromyelitis optica, optic neuritis, and neurofibromatosis; however, the molecular mechanisms of optic nerve damage and death are incompletely understood. Herein we present high spatial resolution MALDI imaging mass spectrometry (IMS) analysis of lipids and proteins to define the molecular anatomy of the human optic nerve. The localization of a number of lipids was observed in discrete anatomical regions corresponding to myelinated and unmyelinated nerve regions as well as to supporting connective tissue, glial cells, and blood vessels. A protein fragment from vimentin, a known intermediate filament marker for astrocytes, was observed surrounding nerved fiber bundles in the lamina cribrosa region. S100B was also found in supporting glial cell regions in the prelaminar region, and the hemoglobin alpha subunit was observed in blood vessel areas. The molecular anatomy of the optic nerve defined by MALDI IMS provides a firm foundation to study biochemical changes in blinding human diseases.

Noise-induced hearing loss alters the temporal dynamics of auditory-nerve responses

PubMed Central

Scheidt, Ryan E.; Kale, Sushrut; Heinz, Michael G.

2010-01-01

Auditory-nerve fibers demonstrate dynamic response properties in that they adapt to rapid changes in sound level, both at the onset and offset of a sound. These dynamic response properties affect temporal coding of stimulus modulations that are perceptually relevant for many sounds such as speech and music. Temporal dynamics have been well characterized in auditory-nerve fibers from normal-hearing animals, but little is known about the effects of sensorineural hearing loss on these dynamics. This study examined the effects of noise-induced hearing loss on the temporal dynamics in auditory-nerve fiber responses from anesthetized chinchillas. Post-stimulus time histograms were computed from responses to 50-ms tones presented at characteristic frequency and 30 dB above fiber threshold. Several response metrics related to temporal dynamics were computed from post-stimulus-time histograms and were compared between normal-hearing and noise-exposed animals. Results indicate that noise-exposed auditory-nerve fibers show significantly reduced response latency, increased onset response and percent adaptation, faster adaptation after onset, and slower recovery after offset. The decrease in response latency only occurred in noise-exposed fibers with significantly reduced frequency selectivity. These changes in temporal dynamics have important implications for temporal envelope coding in hearing-impaired ears, as well as for the design of dynamic compression algorithms for hearing aids. PMID:20696230

5-HT3A -driven green fluorescent protein delineates gustatory fibers innervating sour-responsive taste cells: A labeled line for sour taste?

PubMed

Stratford, J M; Larson, E D; Yang, R; Salcedo, E; Finger, T E

2017-07-01

Taste buds contain multiple cell types with each type expressing receptors and transduction components for a subset of taste qualities. The sour sensing cells, Type III cells, release serotonin (5-HT) in response to the presence of sour (acidic) tastants and this released 5-HT activates 5-HT 3 receptors on the gustatory nerves. We show here, using 5-HT 3A GFP mice, that 5-HT 3 -expressing nerve fibers preferentially contact and receive synaptic contact from Type III taste cells. Further, these 5-HT 3 -expressing nerve fibers terminate in a restricted central-lateral portion of the nucleus of the solitary tract (nTS)-the same area that shows increased c-Fos expression upon presentation of a sour tastant (30 mM citric acid). This acid stimulation also evokes c-Fos in the laterally adjacent mediodorsal spinal trigeminal nucleus (DMSp5), but this trigeminal activation is not associated with the presence of 5-HT 3 -expressing nerve fibers as it is in the nTS. Rather, the neuronal activation in the trigeminal complex likely is attributable to direct depolarization of acid-sensitive trigeminal nerve fibers, for example, polymodal nociceptors, rather than through taste buds. Taken together, these findings suggest that transmission of sour taste information involves communication between Type III taste cells and 5-HT 3 -expressing afferent nerve fibers that project to a restricted portion of the nTS consistent with a crude mapping of taste quality information in the primary gustatory nucleus. © 2017 Wiley Periodicals, Inc.

Differential motor and sensory functional recovery in male but not female adult rats is associated with remyelination rather than axon regeneration after sciatic nerve crush.

PubMed

Tong, Ling-Ling; Ding, You-Quan; Jing, Hong-Bo; Li, Xuan-Yang; Qi, Jian-Guo

2015-05-06

Peripheral nerve functional recovery after injuries relies on both axon regeneration and remyelination. Both axon regeneration and remyelination require intimate interactions between regenerating neurons and their accompanying Schwann cells. Previous studies have shown that motor and sensory neurons are intrinsically different in their regeneration potentials. Moreover, denervated Schwann cells accompanying myelinated motor and sensory axons have distinct gene expression profiles for regeneration-associated growth factors. However, it is unknown whether differential motor and sensory functional recovery exists. If so, the particular one among axon regeneration and remyelination responsible for this difference remains unclear. Here, we aimed to establish an adult rat sciatic nerve crush model with the nonserrated microneedle holders and measured rat motor and sensory functions during regeneration. Furthermore, axon regeneration and remyelination was evaluated by morphometric analysis of electron microscopic images on the basis of nerve fiber classification. Our results showed that Aα fiber-mediated motor function was successfully recovered in both male and female rats. Aδ fiber-mediated sensory function was partially restored in male rats, but completely recovered in female littermates. For both male and female rats, the numbers of regenerated motor and sensory axons were quite comparable. However, remyelination was diverse among myelinated motor and sensory nerve fibers. In detail, Aβ and Aδ fibers incompletely remyelinated in male, but not female rats, whereas Aα fibers fully remyelinated in both sexes. Our result indicated that differential motor and sensory functional recovery in male but not female adult rats is associated with remyelination rather than axon regeneration after sciatic nerve crush.

Retinal nerve fiber layer analysis with scanning laser polarimetry and RTVue-OCT in patients of retinitis pigmentosa.

PubMed

Xue, Kang; Wang, Min; Chen, Junyi; Huang, Xin; Xu, Gezhi

2013-01-01

To measure the thickness of the retinal nerve fiber layer (RNFL) of patients with retinitis pigmentosa (RP) and that of normal controls by scanning laser polarimetry with enhanced corneal compensation (GDxECC) and RTVue-optical coherence tomography (OCT). Fifty-two eyes of 26 patients were included. All patients underwent complete ophthalmological examinations and testing with GDxECC. Twenty-eight of 52 eyes of RP patients underwent RTVue-OCT measurements. A group of 50 eyes of 25 normal subjects (controls) was also included. GDxECC measured RNFL thickness in the peripapillary area in all subjects as well as temporal-superior-nasal-inferior-temporal (TSNIT) parameters, including TSNIT means, superior and inferior region means, TSNIT standard deviation (SD), inter-eye symmetry and nerve fiber indicator (NFI). RTVue-OCT measured the mean, superior, inferior, temporal and nasal quadrant RNFL thickness. In RP patients and controls, TSNIT means by GDxECC were, respectively, 65.00 ± 7.35 and 55.32 ± 5.20. Mean superior quadrant thicknesses were 80.56 ± 10.93 and 69.54 ± 7.45. Mean inferior thicknesses were 80.58 ± 9.34 and 69.12 ± 7.78. SDs were 27.92 ± 5.21 and 28.23 ± 4.01. Inter-eye symmetries were 0.82 ± 0.17 and 0.87 ± 0.09. NFIs were 9.74 ± 8.73 and 16.81 ± 8.13. The differences between mean TSNIT, mean superior and mean inferior quadrant thicknesses and NFIs were statistically significant (p < 0.001). In RTVue-OCT measurements, the differences between mean, superior, inferior and temporal quadrant RNFL thicknesses were statistically significant (p = 0.0322, 0.0213, 0.0387, 0.0005). The RNFL measured by GDxECC was significantly thicker in RP patients than in controls. RNFL thickness measured by RTVue-OCT was significantly greater in RP patients than in controls in the superior, inferior and temporal regions. This contribution provides information on RNFL thickness and discusses the mechanism underlying this phenomenon. Copyright © 2012 S. Karger AG, Basel.

Relevance Vector Machine and Support Vector Machine Classifier Analysis of Scanning Laser Polarimetry Retinal Nerve Fiber Layer Measurements

PubMed Central

Bowd, Christopher; Medeiros, Felipe A.; Zhang, Zuohua; Zangwill, Linda M.; Hao, Jiucang; Lee, Te-Won; Sejnowski, Terrence J.; Weinreb, Robert N.; Goldbaum, Michael H.

2010-01-01

Purpose To classify healthy and glaucomatous eyes using relevance vector machine (RVM) and support vector machine (SVM) learning classifiers trained on retinal nerve fiber layer (RNFL) thickness measurements obtained by scanning laser polarimetry (SLP). Methods Seventy-two eyes of 72 healthy control subjects (average age = 64.3 ± 8.8 years, visual field mean deviation =−0.71 ± 1.2 dB) and 92 eyes of 92 patients with glaucoma (average age = 66.9 ± 8.9 years, visual field mean deviation =−5.32 ± 4.0 dB) were imaged with SLP with variable corneal compensation (GDx VCC; Laser Diagnostic Technologies, San Diego, CA). RVM and SVM learning classifiers were trained and tested on SLP-determined RNFL thickness measurements from 14 standard parameters and 64 sectors (approximately 5.6° each) obtained in the circumpapillary area under the instrument-defined measurement ellipse (total 78 parameters). Tenfold cross-validation was used to train and test RVM and SVM classifiers on unique subsets of the full 164-eye data set and areas under the receiver operating characteristic (AUROC) curve for the classification of eyes in the test set were generated. AUROC curve results from RVM and SVM were compared to those for 14 SLP software-generated global and regional RNFL thickness parameters. Also reported was the AUROC curve for the GDx VCC software-generated nerve fiber indicator (NFI). Results The AUROC curves for RVM and SVM were 0.90 and 0.91, respectively, and increased to 0.93 and 0.94 when the training sets were optimized with sequential forward and backward selection (resulting in reduced dimensional data sets). AUROC curves for optimized RVM and SVM were significantly larger than those for all individual SLP parameters. The AUROC curve for the NFI was 0.87. Conclusions Results from RVM and SVM trained on SLP RNFL thickness measurements are similar and provide accurate classification of glaucomatous and healthy eyes. RVM may be preferable to SVM, because it provides a Bayesian-derived probability of glaucoma as an output. These results suggest that these machine learning classifiers show good potential for glaucoma diagnosis. PMID:15790898

NEURAL ORGANIZATION OF SENSORY INFORMATIONS FOR TASTE,

DTIC Science & Technology

TASTE , ELECTROPHYSIOLOGY), (*NERVES, *TONGUE), NERVE CELLS, NERVE IMPULSES, PHYSIOLOGY, NERVOUS SYSTEM, STIMULATION(PHYSIOLOGY), NERVE FIBERS, RATS...HAMSTERS, STIMULATION(PHYSIOLOGY), PERCEPTION, COOLING, BEHAVIOR, PSYCHOPHYSIOLOGY, TEMPERATURE, THRESHOLDS(PHYSIOLOGY), CHEMORECEPTORS , STATISTICAL ANALYSIS, JAPAN

The influence of botulinum toxin type A (BTX) on the immunohistochemical characteristics of noradrenergic and cholinergic nerve fibers supplying the porcine urinary bladder wall.

PubMed

Lepiarczyk, E; Bossowska, A; Kaleczyc, J; Majewski, M

2011-01-01

Botulinum toxin (BTX) belongs to a family of neurotoxins which strongly influence the function of autonomic neurons supplying the urinary bladder. Accordingly, BTX has been used as an effective drug in experimental therapies of a range of neurogenic bladder disorders. However, there is no detailed information dealing with the influence of BTX on the morphological and chemical properties of nerve fibres supplying the urinary bladder wall. Therefore, the present study investigated, using double-labeling immunohistochemistry, the distribution, relative frequency and chemical coding of cholinergic and noradrenergic nerve fibers supplying the wall of the urinary bladder in normal female pigs (n = 6) and in the pigs (n = 6) after intravesical BTX injections. In the pigs injected with BTX, the number of adrenergic (DbetaH-positive) nerve fibers distributed in the bladder wall (urothelium, submucosa and muscle coat) was distinctly higher while the number of cholinergic (VAChT-positive) nerve terminals was lower than that found in the control animals. Moreover, the injections of BTX resulted in some changes dealing with the chemical coding of the adrenergic nerve fibers. In contrast to the normal pigs, in BTX injected animals the number of DbetaH/NPY- or DbetaH/CGRP-positive axons was higher in the muscle coat, and some fibres distributed in the urothelium and submucosa expressed immunoreactivity to CGRP. The results obtained suggest that the therapeutic effects of BTX on the urinary bladder might be dependent on changes in the distribution and chemical coding of nerve fibers supplying this organ.

[Morphologic studies of the protective role of catechin on kanamycin otoneurotoxicity in SD rats].

PubMed

Liu, Guo-hui; Xie, Ding-hua; Wu, Wei-jing

2002-12-28

To determine the protection of catechin on aminoglycoside antibiotics otoneurotoxicity in SD rats, and observe the morphologic changes of cochlear efferent nerve terminals and outer hair cells after the injection of kanamycin and the feeding of catechin by the stomach tube. Thirty-eight SD rats were randomly assigned into three experimental groups (KM-treated, catechin-treated, KM and catechin in combination) and one control group. The KM-treated group was given kanamycin in a dose of 500 mg.(kg.d)-1 for 14 days. The catechin-treated group was given catechin once by the stomach tube in a dose of 400 mg.(kg.d)-1. Two kinds of medicine were simultaneously given in the KM+ catechin group. Transmission electron microscopy was utilized to observe the subcellular structure of efferent nerve fibers and outer hair cells. The densities of efferent nerve fibers and terminals were examined and the numbers of efferent nerve fibers and terminals were numerated by the surface preparation using modified histochemical staining for acetylcholinesterase (AchE). The damage in the group protected by catechin was relieved compared with the unprotected group. No damage was found in the catechin-treated alone group and controls. The densities and numbers of efferent nerve fibers and terminals were obviously fewer in the unprotected group than in the protected group and controls(P < 0.05). There was no significant difference in the numbers of efferent nerve fibers and terminals of the group protected by catechin compared with the controls and the catechin-treated group (P > 0.05). Catechin significantly protects MOC efferent nerves in kanamycin otoneurotoxicity.

Chitin biological absorbable catheters bridging sural nerve grafts transplanted into sciatic nerve defects promote nerve regeneration.

PubMed

Wang, Zhi-Yong; Wang, Jian-Wei; Qin, Li-Hua; Zhang, Wei-Guang; Zhang, Pei-Xun; Jiang, Bao-Guo

2018-06-01

To investigate the efficacy of chitin biological absorbable catheters in a rat model of autologous nerve transplantation. A segment of sciatic nerve was removed to produce a sciatic nerve defect, and the sural nerve was cut from the ipsilateral leg and used as a graft to bridge the defect, with or without use of a chitin biological absorbable catheter surrounding the graft. The number and morphology of regenerating myelinated fibers, nerve conduction velocity, nerve function index, triceps surae muscle morphology, and sensory function were evaluated at 9 and 12 months after surgery. All of the above parameters were improved in rats in which the nerve graft was bridged with chitin biological absorbable catheters compared with rats without catheters. The results of this study indicate that use of chitin biological absorbable catheters to surround sural nerve grafts bridging sciatic nerve defects promotes recovery of structural, motor, and sensory function and improves muscle fiber morphology. © 2018 John Wiley & Sons Ltd.

CO-LOCALIZATION OF THE VANILLOID CAPSAICIN RECEPTOR AND SUBSTANCE P IN SENSORY NERVE FIBERS INNERVATING COCHLEAR AND VERTEBRO-BASILAR ARTERIES

PubMed Central

VASS, Z.; DAI, C. F.; STEYGER, P. S.; JANCSÓ, G.; TRUNE, D. R.; NUTTALL, A. L.

2014-01-01

Evidence suggests that capsaicin-sensitive substance P (SP)-containing trigeminal ganglion neurons innervate the spiral modiolar artery (SMA), radiating arterioles, and the stria vascularis of the cochlea. Antidromic electrical or chemical stimulation of trigeminal sensory nerves results in neurogenic plasma extravasation in inner ear tissues. The primary aim of this study was to reveal the possible morphological basis of cochlear vascular changes mediated by capsaicin-sensitive sensory nerves. Therefore, the distribution of SP and capsaicin receptor (transient receptor potential vanilloid type 1—TRPV1) was investigated by double immunolabeling to demonstrate the anatomical relationships between the cochlear and vertebro-basilar blood vessels and the trigeminal sensory fiber system. Extensive TRPV1 and SP expression and co-localization were observed in axons within the adventitial layer of the basilar artery, the anterior inferior cerebellar artery, the SMA, and the radiating arterioles of the cochlea. There appears to be a functional relationship between the trigeminal ganglion and the cochlear blood vessels since electrical stimulation of the trigeminal ganglion induced significant plasma extravasation from the SMA and the radiating arterioles. The findings suggest that stimulation of paravascular afferent nerves may result in permeability changes in the basilar and cochlear vascular bed and may contribute to the mechanisms of vertebro-basilar type of headache through the release of SP and stimulation of TPVR1, respectively. We propose that vertigo, tinnitus, and hearing deficits associated with migraine may arise from perturbations of capsaicin-sensitive trigeminal sensory ganglion neurons projecting to the cochlea. PMID:15026132

Automated 3D segmentation of intraretinal layers from optic nerve head optical coherence tomography images

NASA Astrophysics Data System (ADS)

Antony, Bhavna J.; Abràmoff, Michael D.; Lee, Kyungmoo; Sonkova, Pavlina; Gupta, Priya; Kwon, Young; Niemeijer, Meindert; Hu, Zhihong; Garvin, Mona K.

2010-03-01

Optical coherence tomography (OCT), being a noninvasive imaging modality, has begun to find vast use in the diagnosis and management of ocular diseases such as glaucoma, where the retinal nerve fiber layer (RNFL) has been known to thin. Furthermore, the recent availability of the considerably larger volumetric data with spectral-domain OCT has increased the need for new processing techniques. In this paper, we present an automated 3-D graph-theoretic approach for the segmentation of 7 surfaces (6 layers) of the retina from 3-D spectral-domain OCT images centered on the optic nerve head (ONH). The multiple surfaces are detected simultaneously through the computation of a minimum-cost closed set in a vertex-weighted graph constructed using edge/regional information, and subject to a priori determined varying surface interaction and smoothness constraints. The method also addresses the challenges posed by presence of the large blood vessels and the optic disc. The algorithm was compared to the average manual tracings of two observers on a total of 15 volumetric scans, and the border positioning error was found to be 7.25 +/- 1.08 μm and 8.94 +/- 3.76 μm for the normal and glaucomatous eyes, respectively. The RNFL thickness was also computed for 26 normal and 70 glaucomatous scans where the glaucomatous eyes showed a significant thinning (p < 0.01, mean thickness 73.7 +/- 32.7 μm in normal eyes versus 60.4 +/- 25.2 μm in glaucomatous eyes).

Correlation between central corneal thickness and visual field defects, cup to disc ratio and retinal nerve fiber layer thickness in primary open angle glaucoma patients.

PubMed

Sarfraz, Muhammad Haroon; Mehboob, Mohammad Asim; Haq, Rana Intisar Ul

2017-01-01

To evaluate the correlation between Central Corneal Thickness (CCT) and Visual Field (VF) defect parameters like Mean Deviation (MD) and Pattern Standard Deviation (PSD), Cup-to-Disc Ratio (CDR) and Retinal Nerve Fibre Layer Thickness (RNFL-T) in Primary Open-Angle Glaucoma (POAG) patients. This cross sectional study was conducted at Armed Forces Institute of Ophthalmology (AFIO), Rawalpindi from September 2015 to September 2016. Sixty eyes of 30 patients with diagnosed POAG were analysed. Correlation of CCT with other variables was studied. Mean age of study population was 43.13±7.54 years. Out of 30 patients, 19 (63.33%) were males and 11 (36.67%) were females. Mean CCT, MD, PSD, CDR and RNFL-T of study population was 528.57±25.47µm, -9.11±3.07, 6.93±2.73, 0.63±0.13 and 77.79±10.44µm respectively. There was significant correlation of CCT with MD, PSD and CDR (r=-0.52, p<0.001; r=-0.59, p<0.001;r=-0.41, p=0.001 respectively). The correlation of CCT with RNFL-T was not statistically significant (r=-0.14, p=0.284). Central corneal thickness had significant correlation with visual field parameters like mean deviation and pattern standard deviation, as well as with cup-to-disc ratio. However, central corneal thickness had no significant relationship with retinal nerve fibre layer thickness.

MELANOPHORE BANDS AND AREAS DUE TO NERVE CUTTING, IN RELATION TO THE PROTRACTED ACTIVITY OF NERVES

PubMed Central

Parker, G. H.

1941-01-01

1. When appropriate chromatic nerves are cut caudal bands, cephalic areas, and the pelvic fins of the catfish Ameiurus darken. In pale fishes all these areas will sooner or later blanch. By recutting their nerves all such blanched areas will darken again. 2. These observations show that the darkening of caudal bands, areas, and fins on cutting their nerves is not due to paralysis (Brücke), to the obstruction of central influences such as inhibition (Zoond and Eyre), nor to vasomotor disturbances (Hogben), but to activities emanating from the cut itself. 3. The chief agents concerned with the color changes in Ameiurus are three: intermedin from the pituitary gland, acetylcholine from the dispersing nerves (cholinergic fibers), and adrenalin from the concentrating nerves (adrenergic fibers). The first two darken the fish; the third blanches it. In darkening the dispersing nerves appear to initiate the process and to be followed and substantially supplemented by intermedin. 4. Caudal bands blanch by lateral invasion, cephalic areas by lateral invasion and internal disintegration, and pelvic fins by a uniform process of general loss of tint equivalent to internal disintegration. 5. Adrenalin may be carried in such an oil as olive oil and may therefore act as a lipohumor; it is soluble in water and hence may act as a hydrohumor. In lateral invasion (caudal bands, cephalic areas) it probably acts as a lipohumor and in internal disintegration (cephalic areas, pelvic fins) it probably plays the part of a hydrohumor. 6. The duration of the activity of dispersing nerves after they had been cut was tested by means of the oscillograph, by anesthetizing blocks, and by cold-blocks. The nerves of Ameiurus proved to be unsatisfactory for oscillograph tests. An anesthetizing block, magnesium sulfate, is only partly satisfactory. A cold-block, 0°C., is successful to a limited degree. 7. By means of a cold-block it can be shown that dispersing autonomic nerve fibers in Ameiurus can continue in activity for at least 6½ hours. It is not known how much longer they may remain active. So far as the duration of their activity is concerned dispersing nerve fibers in this fish are unlike other types of nerve fibers usually studied. PMID:19873231

NRP-1 Receptor Expression Mismatch in Skin of Subjects with Experimental and Diabetic Small Fiber Neuropathy

PubMed Central

Van Acker, Nathalie; Ragé, Michael; Vermeirsch, Hilde; Schrijvers, Dorien; Nuydens, Rony; Byttebier, Geert; Timmers, Maarten; De Schepper, Stefanie; Streffer, Johannes; Andries, Luc; Plaghki, Léon; Cras, Patrick; Meert, Theo

2016-01-01

The in vivo cutaneous nerve regeneration model using capsaicin is applied extensively to study the regenerative mechanisms and therapeutic efficacy of disease modifying molecules for small fiber neuropathy (SFN). Since mismatches between functional and morphological nerve fiber recovery are described for this model, we aimed at determining the capability of the capsaicin model to truly mimic the morphological manifestations of SFN in diabetes. As nerve and blood vessel growth and regenerative capacities are defective in diabetes, we focused on studying the key regulator of these processes, the neuropilin-1 (NRP-1)/semaphorin pathway. This led us to the evaluation of NRP-1 receptor expression in epidermis and dermis of subjects presenting experimentally induced small fiber neuropathy, diabetic polyneuropathy and of diabetic subjects without clinical signs of small fiber neuropathy. The NRP-1 receptor was co-stained with CD31 vessel-marker using immunofluorescence and analyzed with Definiens® technology. This study indicates that capsaicin application results in significant loss of epidermal NRP-1 receptor expression, whereas diabetic subjects presenting small fiber neuropathy show full epidermal NRP-1 expression in contrast to the basal expression pattern seen in healthy controls. Capsaicin induced a decrease in dermal non-vascular NRP-1 receptor expression which did not appear in diabetic polyneuropathy. We can conclude that the capsaicin model does not mimic diabetic neuropathy related changes for cutaneous NRP-1 receptor expression. In addition, our data suggest that NRP-1 might play an important role in epidermal nerve fiber loss and/or defective regeneration and that NRP-1 receptor could change the epidermal environment to a nerve fiber repellant bed possibly through Sem3A in diabetes. PMID:27598321

Taste bud-derived BDNF maintains innervation of a subset of TrkB-expressing gustatory nerve fibers

PubMed Central

Tang, Tao; Rios-Pilier, Jennifer; Krimm, Robin

2018-01-01

Taste receptor cells transduce different types of taste stimuli and transmit this information to gustatory neurons that carry it to the brain. Taste receptor cells turn over continuously in adulthood, requiring constant new innervation from nerve fibers. Therefore, the maintenance of innervation to taste buds is an active process mediated by many factors, including brain-derived neurotrophic factor (BDNF). Specifically, 40% of taste bud innervation is lost when Bdnf is removed during adulthood. Here we speculated that not all gustatory nerve fibers express the BDNF receptor, TrkB, resulting in subsets of neurons that vary in their response to BDNF. However, it is also possible that the partial loss of innervation occurred because the Bdnf gene was not effectively removed. To test these possibilities, we first determined that not all gustatory nerve fibers express the TrkB receptor in adult mice. We then verified the efficiency of Bdnf removal specifically in taste buds of K14-CreER:Bdnf mice and found that Bdnf expression was reduced to 1%, indicating efficient Bdnf gene recombination. BDNF removal resulted in a 55% loss of TrkB-expressing nerve fibers, which was greater than the loss of P2X3-positive fibers (39%), likely because taste buds were innervated by P2X3+/TrkB− fibers that were unaffected by BDNF removal. We conclude that gustatory innervation consists of both TrkB-positive and TrkB-negative taste fibers and that BDNF is specifically important for maintaining TrkB-positive innervation to taste buds. In addition, although taste bud size was not affected by inducible Bdnf removal, the expression of the γ subunit of the ENaC channel was reduced. So, BDNF may regulate expression of some molecular components of taste transduction pathways. PMID:28600222

Comparative study of peripheral neuropathy and nerve regeneration in NOD and ICR diabetic mice.

PubMed

Homs, Judit; Ariza, Lorena; Pagès, Gemma; Verdú, Enrique; Casals, Laura; Udina, Esther; Chillón, Miguel; Bosch, Assumpció; Navarro, Xavier

2011-09-01

The non-obese diabetic (NOD) mouse was suggested as an adequate model for diabetic autonomic neuropathy. We evaluated sensory-motor neuropathy and nerve regeneration following sciatic nerve crush in NOD males rendered diabetic by multiple low doses of streptozotocin, in comparison with similarly treated Institute for Cancer Research (ICR) mice, a widely used model for type I diabetes. Neurophysiological values for both strains showed a decline in motor and sensory nerve conduction velocity at 7 and 8 weeks after induction of diabetes in the intact hindlimb. However, amplitudes of compound muscle and sensory action potentials (CMAPs and CNAPs) were significantly reduced in NOD but not in ICR diabetic mice. Morphometrical analysis showed myelinated fiber loss in highly hyperglycemic NOD mice, but no significant changes in fiber size. There was a reduction of intraepidermal nerve fibers, more pronounced in NOD than in ICR diabetic mice. Interestingly, aldose reductase and poly(ADP-ribose) polymerase (PARP) activities were increased already at 1 week of hyperglycemia, persisting until the end of the experiment in both strains. Muscle and nerve reinnervation was delayed in diabetic mice following sciatic nerve crush, being more marked in NOD mice. Thus, diabetes of mid-duration induces more severe peripheral neuropathy and slower nerve regeneration in NOD than in ICR mice. © 2011 Peripheral Nerve Society.

Analysis of the chicken retina with an adaptive optics multiphoton microscope.

PubMed

Bueno, Juan M; Giakoumaki, Anastasia; Gualda, Emilio J; Schaeffel, Frank; Artal, Pablo

2011-06-01

The structure and organization of the chicken retina has been investigated with an adaptive optics multiphoton imaging microscope in a backward configuration. Non-stained flat-mounted retinal tissues were imaged at different depths, from the retinal nerve fiber layer to the outer segment, by detecting the intrinsic nonlinear fluorescent signal. From the stacks of images corresponding to the different retinal layers, volume renderings of the entire retina were reconstructed. The density of photoreceptors and ganglion cells layer were directly estimated from the images as a function of the retinal eccentricity. The maximum anatomical resolving power at different retinal eccentricities was also calculated. This technique could be used for a better characterization of retinal alterations during myopia development, and may be useful for visualization of retinal pathologies and intoxication during pharmacological studies.

Spectral-Domain Optical Coherence Tomography for Glaucoma Diagnosis

PubMed Central

Gracitelli, Carolina P.B; Abe, Ricardo Y; Medeiros, Felipe A

2015-01-01

Identification of structural damage to the optic nerve and retinal nerve fiber layer (RNFL) is an essential component of diagnosis and management of glaucoma. The introduction of spectral-domain OCT (SD-OCT) has allowed objective quantification of damage to these structures with unprecedented resolution. In addition, recent attention has been directed towards imaging the macular area for quantifying loss of neural tissue caused by the disease. Many studies have evaluated and compared the diagnostic accuracies of a variety of parameters that can be obtained from imaging these areas of the ocular fundus. In this article, we critically review the existing literature evaluating the diagnostic accuracy of SD-OCT in glaucoma and we discuss issues related to how SD-OCT results should be incorporated into clinical practice. PMID:26069519

Coexistence of salusin and vasopressin in the rat hypothalamo-hypophyseal system.

PubMed

Takenoya, Fumiko; Hori, Tomoko; Kageyama, Haruaki; Funahashi, Hisayuki; Takeuchi, Masao; Kitamura, Yoshitaka; Shichiri, Masayoshi; Shioda, Seiji

2005-09-09

Salusins are two newly discovered TOR-related peptides consisting of 28 and 20 amino acids and designated salusin-alpha and salusin-beta, respectively. Using immunohistochemistry techniques, salusin-like immunoreactivity was detected in the rat hypothalamo-neurohypophyseal tract and immunopositive cells were distributed in the suprachiasmatic, supraoptic and paraventricular nucleus. In the paraventricular nucleus, salusin-like immunoreactivity was observed both in parvocellular and magnocellular neurons. Many salusin-positive nerve fibers and their terminals were identified in the internal layer of the median eminence and posterior pituitary. Less intense salusin-positive staining of fibers and terminals was found in the suprachiasmatic nucleus and external layer of the median eminence. Dual immunostaining was performed to determine if salusin coexisted with vasopressin or oxytocin in the hypothalamus. Most of the salusin-like immunoreactivity was detected in vasopressin- but not in oxytocin-containing neurons in these nuclei. The functional significance of the coexistence of salusin with vasopressin is discussed, including the possibility that salusin participates in the regulation of blood pressure.

Optic Nerve Disorders

MedlinePlus

The optic nerve is a bundle of more than 1 million nerve fibers that carry visual messages. You have one connecting ... retina) to your brain. Damage to an optic nerve can cause vision loss. The type of vision ...

Histomorphometric and Ultrastructural Evaluation of Long-Term Alpha Lipoic Acid and Vitamin B12 Use After Experimental Sciatic Nerve Injury in Rats.

PubMed

Arikan, Murat; Togral, Guray; Hasturk, Askin Esen; Horasanli, Bahriye; Helvacioglu, Fatma; Dagdeviren, Atilla; Tekindal, Mustafa Agah; Parpucu, Murat

2016-01-01

To analyze the therapeutic effects of long-term alpha lipoic acid (A-LA) and vitamin B12 use via histomorphometric methods and electron microscopy in the transected sciatic nerves of rats. Forty rats were randomized into five groups (n=8/group). In group I, 1 cm segment of sciatic nerve was resected without any other intervention. In group II (sham), following right sciatic nerve transection, primary epineurial anastomosis was performed by placing the edges of the nerve end-to-end. In group III (saline), after right sciatic nerve transection, the ends of the nerves were brought together and closed after application of intraperitoneal physiologic saline. In group IV, 2 mg/kg of alpha lipoic acid and in group V, 2 mg/kg of vitamin B12 was administered intraperitoneally before surgical intervention. Histomorphometric and electron microscopic analyses revealed that vitamin B12 did not prevent structural changes, abnormal myelination and g-ratio deviations regarding the functional aspects of the sciatic nerve. Alpha lipoic acid was more effective in restructuring the histomorphometric and structural aspects of the nerve with more myelinated fibers with optimal values (0.55-0.68) than vitamin B12 groups, in which the number of myelinated nerve fibers significantly decreased at optimal intervals (0.55-0.68). A-LA administration following peripheral nerve transection injury is more effective in promoting nerve healing regarding the structural aspects of the sciatic nerve compared to vitamin B12 and also myelination of nerve fibers by increasing g-values.

Shock wave treatment improves nerve regeneration in the rat.

PubMed

Mense, Siegfried; Hoheisel, Ulrich

2013-05-01

The aims of the experiments were to: (1) determine whether low-energy shock wave treatment accelerates the recovery of muscle sensitivity and functionality after a nerve lesion; and (2) assess the effect of shock waves on the regeneration of injured nerve fibers. After compression of a muscle nerve in rats the effects of shock wave treatment on the sequelae of the lesion were tested. In non-anesthetized animals, pressure pain thresholds and exploratory activity were determined. The influence of the treatment on the distance of nerve regeneration was studied in immunohistochemical experiments. Both behavioral and immunohistochemical data show that shock wave treatment accelerates the recovery of muscle sensitivity and functionality and promotes regeneration of injured nerve fibers. Treatment with focused shock waves induces an improvement of nerve regeneration in a rodent model of nerve compression. Copyright © 2012 Wiley Periodicals, Inc.

Palisade endings in extraocular muscles of the monkey are immunoreactive for choline acetyltransferase and vesicular acetylcholine transporter.

PubMed

Konakci, Kadriye Zeynep; Streicher, Johannes; Hoetzenecker, Wolfram; Haberl, Ines; Blumer, Michael Josef Franz; Wieczorek, Grazyna; Meingassner, Josef Gottfried; Paal, Szabolcs Levente; Holzinger, Daniel; Lukas, Julius-Robert; Blumer, Roland

2005-12-01

To analyze palisade endings in extraocular muscles (EOMs) of a primate species and to examine our previous findings in cat that palisade endings are putative effector organs. Eleven monkeys (Macaca fascicularis) of both sexes, between 4 and 6 years of age were analyzed. Whole EOM myotendons were immunostained with four combinations of triple-fluorescent labeling and examined by confocal laser scanning microscopy. Labeling included antibodies against choline acetyltransferase (ChAT), vesicular acetylcholine transporter (VAChT), neurofilament, and synaptophysin. Muscle fibers were counterstained with phalloidin. Palisade endings were observed in all monkey EOMs. Nerve fibers extended from the muscle into the tendon and looped back to divide into a terminal arborization (palisade ending) around a single muscle fiber tip. In approximately 30% of the cases, nerve fibers supplying palisade endings often established motor terminals outside the palisade complex. Nerve fibers forming palisade endings were ChAT-neurofilament positive. Axonal branches of palisade endings were ChAT-neurofilament positive as well. All palisade nerve terminals exhibited ChAT-synaptophysin immunoreactivity. Within the palisade complex, palisade nerve terminals exhibited VAChT immunoreactivity. All palisade nerve terminals were VAChT-synaptophysin immunoreactive. The results confirm that in the monkey, palisade endings contain acetylcholine and are therefore most likely effector organs. Palisade endings are also present in human EOMs and because of their location at the myotendinous junction, these organs are of crucial interest for strabismus surgery.

Dienogest reduces proliferation, NGF expression and nerve fiber density in human adenomyosis.

PubMed

Takeuchi, Arisa; Koga, Kaori; Miyashita, Mariko; Makabe, Tomoko; Sue, Fusako; Harada, Miyuki; Hirata, Tetsuya; Hirota, Yasushi; Fujii, Tomoyuki; Osuga, Yutaka

2016-12-01

To evaluate the in vivo effect of dienogest on proliferation, apoptosis, aromatase expression, vascular density, nerve growth factor (NGF) expression and nerve fiber density in human adenomyosis tissue. Twelve women who underwent hysterectomy for adenomyosis were enrolled. Six patients received dienogest treatment prior to hysterectomy (dienogest group), and age-matched six patients who had not received any hormonal treatment for ≥3 months before surgery (control group). Cell proliferation, vascular and nerve fiber density in adenomyosis tissue were evaluated by staining for Ki67, von Willebrand factor and PGP9.5, respectively. Apoptosis was detected using the TUNEL assay. The expression aromatase and NGF were evaluated by staining for corresponding antibodies. The proportion of Ki67 positive epithelial cells was significantly lower in samples from dienogest-treated patients in comparison with controls (p<0.05). The density of blood vessels in adenomyosis was marginally lower in the dienogest group in comparison with controls but statistical significance was not reached (p=0.07). The intensity of NGF expression and the density of nerve fibers were significantly lower in the dienogest group compared with controls (p<0.05 for both). This study demonstrates that adenomyosis, taken from patients treated with dienogest, shows remarkable histological features, such as reductions in proliferation, NGF expression and nerve fiber density. These findings indicate the impact of dienogest on local histological events, and explains its therapeutic effect on adenomyosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Automatic estimation of retinal nerve fiber bundle orientation in SD-OCT images using a structure-oriented smoothing filter

NASA Astrophysics Data System (ADS)

Ghafaryasl, Babak; Baart, Robert; de Boer, Johannes F.; Vermeer, Koenraad A.; van Vliet, Lucas J.

2017-02-01

Optical coherence tomography (OCT) yields high-resolution, three-dimensional images of the retina. A better understanding of retinal nerve fiber bundle (RNFB) trajectories in combination with visual field data may be used for future diagnosis and monitoring of glaucoma. However, manual tracing of these bundles is a tedious task. In this work, we present an automatic technique to estimate the orientation of RNFBs from volumetric OCT scans. Our method consists of several steps, starting from automatic segmentation of the RNFL. Then, a stack of en face images around the posterior nerve fiber layer interface was extracted. The image showing the best visibility of RNFB trajectories was selected for further processing. After denoising the selected en face image, a semblance structure-oriented filter was applied to probe the strength of local linear structure in a discrete set of orientations creating an orientation space. Gaussian filtering along the orientation axis in this space is used to find the dominant orientation. Next, a confidence map was created to supplement the estimated orientation. This confidence map was used as pixel weight in normalized convolution to regularize the semblance filter response after which a new orientation estimate can be obtained. Finally, after several iterations an orientation field corresponding to the strongest local orientation was obtained. The RNFB orientations of six macular scans from three subjects were estimated. For all scans, visual inspection shows a good agreement between the estimated orientation fields and the RNFB trajectories in the en face images. Additionally, a good correlation between the orientation fields of two scans of the same subject was observed. Our method was also applied to a larger field of view around the macula. Manual tracing of the RNFB trajectories shows a good agreement with the automatically obtained streamlines obtained by fiber tracking.

Anatomic assessment of sympathetic peri-arterial renal nerves in man.

PubMed

Sakakura, Kenichi; Ladich, Elena; Cheng, Qi; Otsuka, Fumiyuki; Yahagi, Kazuyuki; Fowler, David R; Kolodgie, Frank D; Virmani, Renu; Joner, Michael

2014-08-19

Although renal sympathetic denervation therapy has shown promising results in patients with resistant hypertension, the human anatomy of peri-arterial renal nerves is poorly understood. The aim of our study was to investigate the anatomic distribution of peri-arterial sympathetic nerves around human renal arteries. Bilateral renal arteries were collected from human autopsy subjects, and peri-arterial renal nerve anatomy was examined by using morphometric software. The ratio of afferent to efferent nerve fibers was investigated by dual immunofluorescence staining using antibodies targeted for anti-tyrosine hydroxylase and anti-calcitonin gene-related peptide. A total of 10,329 nerves were identified from 20 (12 hypertensive and 8 nonhypertensive) patients. The mean individual number of nerves in the proximal and middle segments was similar (39.6 ± 16.7 per section and 39.9 ± 1 3.9 per section), whereas the distal segment showed fewer nerves (33.6 ± 13.1 per section) (p = 0.01). Mean subject-specific nerve distance to arterial lumen was greatest in proximal segments (3.40 ± 0.78 mm), followed by middle segments (3.10 ± 0.69 mm), and least in distal segments (2.60 ± 0.77 mm) (p < 0.001). The mean number of nerves in the ventral region (11.0 ± 3.5 per section) was greater compared with the dorsal region (6.2 ± 3.0 per section) (p < 0.001). Efferent nerve fibers were predominant (tyrosine hydroxylase/calcitonin gene-related peptide ratio 25.1 ± 33.4; p < 0.0001). Nerve anatomy in hypertensive patients was not considerably different compared with nonhypertensive patients. The density of peri-arterial renal sympathetic nerve fibers is lower in distal segments and dorsal locations. There is a clear predominance of efferent nerve fibers, with decreasing prevalence of afferent nerves from proximal to distal peri-arterial and renal parenchyma. Understanding these anatomic patterns is important for refinement of renal denervation procedures. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Optic neuropathies: the tip of the neurodegeneration iceberg

PubMed Central

Carelli, Valerio; La Morgia, Chiara; Ross-Cisneros, Fred N.; Sadun, Alfredo A.

2017-01-01

Abstract The optic nerve and the cells that give origin to its 1.2 million axons, the retinal ganglion cells (RGCs), are particularly vulnerable to neurodegeneration related to mitochondrial dysfunction. Optic neuropathies may range from non-syndromic genetic entities, to rare syndromic multisystem diseases with optic atrophy such as mitochondrial encephalomyopathies, to age-related neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease where optic nerve involvement has, until recently, been a relatively overlooked feature. New tools are available to thoroughly investigate optic nerve function, allowing unparalleled access to this part of the central nervous system. Understanding the molecular pathophysiology of RGC neurodegeneration and optic atrophy, is key to broadly understanding the pathogenesis of neurodegenerative disorders, for monitoring their progression in describing the natural history, and ultimately as outcome measures to evaluate therapies. In this review, the different layers, from molecular to anatomical, that may contribute to RGC neurodegeneration and optic atrophy are tackled in an integrated way, considering all relevant players. These include RGC dendrites, cell bodies and axons, the unmyelinated retinal nerve fiber layer and the myelinated post-laminar axons, as well as olygodendrocytes and astrocytes, looked for unconventional functions. Dysfunctional mitochondrial dynamics, transport, homeostatic control of mitobiogenesis and mitophagic removal, as well as specific propensity to apoptosis may target differently cell types and anatomical settings. Ultimately, we can envisage new investigative approaches and therapeutic options that will speed the early diagnosis of neurodegenerative diseases and their cure. PMID:28977448

Palisade endings are present in canine extraocular muscles and have a cholinergic phenotype.

PubMed

Rungaldier, Stefanie; Pomikal, Christine; Streicher, Johannes; Blumer, Roland

2009-11-20

Classical proprioceptors, like Golgi tendon organs and muscle spindles are absent in the extraocular muscles (EOMs) of most mammals. Instead, a nerve end organ was detected in the EOMs of each species including sheep, cat, rabbit, rat, monkey, and human examined so far: the palisade ending. Until now no clear evidence appeared that palisade endings are also present in canine EOMs. Here, we analyzed dog EOMs by confocal laser scanning microscopy, 3D reconstruction, and transmission electron microscopy. In EOM wholemount preparations stained with antibodies against neurofilament and synaptophysin we could demonstrate typical palisade endings. Nerve fibers coming from the muscle extend into the tendon. There, the nerve fibers turn 180 degrees and return to branch into preterminal axons which establish nerve terminals around a single muscle fiber tip. Fine structural analysis revealed that each palisade ending in dog EOMs establish nerve terminals on the tendon. In some palisade endings we found nerve terminals contacting the muscle fiber as well. Such neuromuscular contacts have a basal lamina in the synaptic cleft. By using an antibody against choline acetyltransferase (ChAT) we proved that canine palisade endings are ChAT-immunoreactive. This study shows that palisade endings are present in canine EOMs. In line with prior findings in cat and monkey, palisade endings in dog have a cholinergic phenotype.

Local Xenotransplantation of Bone Marrow Derived Mast Cells (BMMCs) Improves Functional Recovery of Transected Sciatic Nerve in Cat: A Novel Approach in Cell Therapy.

PubMed

Mohammadi, Rahim; Anousheh, Dana; Alaei, Mohammad-Hazhir; Nikpasand, Amin; Rostami, Hawdam; Shahrooz, Rasoul

2018-04-01

To determine the effects of bone marrow derived mast cells (BMMCs) on functional recovery of transected sciatic nerve in animal model of cat. A 20-mm sciatic nerve defect was bridged using a silicone nerve guide filled with BMMCs in BMMC group. In Sham-surgery group (SHAM), the sciatic nerve was only exposed and manipulated. In control group (SILOCONE) the gap was repaired with a silicone nerve guide and both ends were sealed using sterile Vaseline to avoid leakage and the nerve guide was filled with 100 μL of phosphate-buffered saline alone. In cell treated group ([SILOCONE/BMMC) the nerve guide was filled with 100 μL BMMCs (2× 106 cells/100 μL). The regenerated nerve fibers were studied, biomechanically, histologically and immunohiscochemically 6 months later. Biomechanical studies confirmed faster recovery of regenerated axons in BMMCs transplanted animals compared to control group ( p <0.05). Morphometric indices of the regenerated fibers showed that the number and diameter of the myelinated fibers were significantly higher in BMMCs transplanted animals than in control group ( p <0.05). In immunohistochemistry, location of reactions to S-100 in BMMCs transplanted animals was clearly more positive than that in control group. BMMCs xenotransplantation could be considered as a readily accessible source of cells that could improve recovery of transected sciatic nerve.

Spinal cord projections of the rat main forelimb nerves, studied by transganglionic transport of WGA-HRP and by the disappearance of acid phosphatase.

PubMed

Castro-Lopes, J M; Coimbra, A

1991-03-01

The spinal cord projections of the 3 main forelimb nerves-median, radial and ulnar, were studied in the rat dorsal horn with transganglionic transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP), or using the disappearance of fluoride resistant acid phosphatase (FRAP) after nerve section. The projection patterns in lamina II were similar following the two procedures. The median and the radial nerve fibers projected to the medial and the intermediate thirds, respectively, of the dorsal horn lamina II in spinal cord segments C4-C8. The ulnar nerve projected to segments C6-C8 between the areas occupied by the other two nerves. The FRAP method also showed that the lateral part of lamina II, which was not filled by radial nerve fibers, received the projections from the dorsal cutaneous branches of cervical spinal nerves. In addition, FRAP disappeared from the medial end of segment T1 after skin incisions extending from the medial brachium to the axilla, which seemed due to severance of the cutaneous branchlets of the lateral anterior thoracic nerve. The FRAP procedure is thus sensitive enough to detect fibers in lamina II arising from small peripheral nerves, and may be used as an alternative to the anterograde tracing methods whenever there are no overlapping projections.

Virtual Instrumentation for a Fiber-Optics-Based Artificial Nerve

NASA Technical Reports Server (NTRS)

Lyons, Donald R.; Kyaw, Thet Mon; Griffin, DeVon (Technical Monitor)

2001-01-01

A LabView-based computer interface for fiber-optic artificial nerves has been devised as a Masters thesis project. This project involves the use of outputs from wavelength multiplexed optical fiber sensors (artificial nerves), which are capable of producing dense optical data outputs for physical measurements. The potential advantages of using optical fiber sensors for sensory function restoration is the fact that well defined WDM-modulated signals can be transmitted to and from the sensing region allowing networked units to replace low-level nerve functions for persons desirous of "intelligent artificial limbs." Various FO sensors can be designed with high sensitivity and the ability to be interfaced with a wide range of devices including miniature shielded electrical conversion units. Our Virtual Instrument (VI) interface software package was developed using LabView's "Laboratory Virtual Instrument Engineering Workbench" package. The virtual instrument has been configured to arrange and encode the data to develop an intelligent response in the form of encoded digitized signal outputs. The architectural layout of our nervous system is such that different touch stimuli from different artificial fiber-optic nerve points correspond to gratings of a distinct resonant wavelength and physical location along the optical fiber. Thus, when an automated, tunable diode laser sends scans, the wavelength spectrum of the artificial nerve, it triggers responses that are encoded with different touch stimuli by way wavelength shifts in the reflected Bragg resonances. The reflected light is detected and a resulting analog signal is fed into ADC1 board and DAQ card. Finally, the software has been written such that the experimenter is able to set the response range during data acquisition.

Automated detection of nerve fiber layer defects on retinal fundus images using fully convolutional network for early diagnosis of glaucoma

NASA Astrophysics Data System (ADS)

Watanabe, Ryusuke; Muramatsu, Chisako; Ishida, Kyoko; Sawada, Akira; Hatanaka, Yuji; Yamamoto, Tetsuya; Fujita, Hiroshi

2017-03-01

Early detection of glaucoma is important to slow down progression of the disease and to prevent total vision loss. We have been studying an automated scheme for detection of a retinal nerve fiber layer defect (NFLD), which is one of the earliest signs of glaucoma on retinal fundus images. In our previous study, we proposed a multi-step detection scheme which consists of Gabor filtering, clustering and adaptive thresholding. The problems of the previous method were that the number of false positives (FPs) was still large and that the method included too many rules. In attempt to solve these problems, we investigated the end-to-end learning system without pre-specified features. A deep convolutional neural network (DCNN) with deconvolutional layers was trained to detect NFLD regions. In this preliminary investigation, we investigated effective ways of preparing the input images and compared the detection results. The optimal result was then compared with the result obtained by the previous method. DCNN training was carried out using original images of abnormal cases, original images of both normal and abnormal cases, ellipse-based polar transformed images, and transformed half images. The result showed that use of both normal and abnormal cases increased the sensitivity as well as the number of FPs. Although NFLDs are visualized with the highest contrast in green plane, the use of color images provided higher sensitivity than the use of green image only. The free response receiver operating characteristic curve using the transformed color images, which was the best among seven different sets studied, was comparable to that of the previous method. Use of DCNN has a potential to improve the generalizability of automated detection method of NFLDs and may be useful in assisting glaucoma diagnosis on retinal fundus images.

Stochastic information transfer from cochlear implant electrodes to auditory nerve fibers

NASA Astrophysics Data System (ADS)

Gao, Xiao; Grayden, David B.; McDonnell, Mark D.

2014-08-01

Cochlear implants, also called bionic ears, are implanted neural prostheses that can restore lost human hearing function by direct electrical stimulation of auditory nerve fibers. Previously, an information-theoretic framework for numerically estimating the optimal number of electrodes in cochlear implants has been devised. This approach relies on a model of stochastic action potential generation and a discrete memoryless channel model of the interface between the array of electrodes and the auditory nerve fibers. Using these models, the stochastic information transfer from cochlear implant electrodes to auditory nerve fibers is estimated from the mutual information between channel inputs (the locations of electrodes) and channel outputs (the set of electrode-activated nerve fibers). Here we describe a revised model of the channel output in the framework that avoids the side effects caused by an "ambiguity state" in the original model and also makes fewer assumptions about perceptual processing in the brain. A detailed comparison of how different assumptions on fibers and current spread modes impact on the information transfer in the original model and in the revised model is presented. We also mathematically derive an upper bound on the mutual information in the revised model, which becomes tighter as the number of electrodes increases. We found that the revised model leads to a significantly larger maximum mutual information and corresponding number of electrodes compared with the original model and conclude that the assumptions made in this part of the modeling framework are crucial to the model's overall utility.

Local delivery of glial cell line-derived neurotrophic factor improves facial nerve regeneration after late repair.

PubMed

Barras, Florian M; Kuntzer, Thierry; Zurn, Anne D; Pasche, Philippe

2009-05-01

Facial nerve regeneration is limited in some clinical situations: in long grafts, by aged patients, and when the delay between nerve lesion and repair is prolonged. This deficient regeneration is due to the limited number of regenerating nerve fibers, their immaturity and the unresponsiveness of Schwann cells after a long period of denervation. This study proposes to apply glial cell line-derived neurotrophic factor (GDNF) on facial nerve grafts via nerve guidance channels to improve the regeneration. Two situations were evaluated: immediate and delayed grafts (repair 7 months after the lesion). Each group contained three subgroups: a) graft without channel, b) graft with a channel without neurotrophic factor; and c) graft with a GDNF-releasing channel. A functional analysis was performed with clinical observation of facial nerve function, and nerve conduction study at 6 weeks. Histological analysis was performed with the count of number of myelinated fibers within the graft, and distally to the graft. Central evaluation was assessed with Fluoro-Ruby retrograde labeling and Nissl staining. This study showed that GDNF allowed an increase in the number and the maturation of nerve fibers, as well as the number of retrogradely labeled neurons in delayed anastomoses. On the contrary, after immediate repair, the regenerated nerves in the presence of GDNF showed inferior results compared to the other groups. GDNF is a potent neurotrophic factor to improve facial nerve regeneration in grafts performed several months after the nerve lesion. However, GDNF should not be used for immediate repair, as it possibly inhibits the nerve regeneration.

Fiber type-specific afferent nerve activity induced by transient contractions of rat bladder smooth muscle in pathological states

PubMed Central

Kuga, Nahoko; Tanioka, Asao; Hagihara, Koichiro; Kawai, Tomoyuki

2017-01-01

Bladder smooth muscle shows spontaneous phasic contractions, which undergo a variety of abnormal changes depending on pathological conditions. How abnormal contractions affect the activity of bladder afferent nerves remains to be fully tested. In this study, we examined the relationship between transient increases in bladder pressure, representing transient contraction of bladder smooth muscle, and spiking patterns of bladder afferent fibers of the L6 dorsal root, in rat pathological models. All recordings were performed at a bladder pressure of approximately 10 cmH2O by maintaining the degree of bladder filling. In the cyclophosphamide-induced model, both Aδ and C fibers showed increased sensitivity to transient bladder pressure increases. In the prostaglandin E2-induced model, Aδ fibers, but not C fibers, specifically showed overexcitation that was time-locked with transient bladder pressure increases. These fiber type-specific changes in nerve spike patterns may underlie the symptoms of urinary bladder diseases. PMID:29267380

Diagnostic Accuracy of Spectralis SD OCT Automated Macular Layers Segmentation to Discriminate Normal from Early Glaucomatous Eyes.

PubMed

Pazos, Marta; Dyrda, Agnieszka Anna; Biarnés, Marc; Gómez, Alicia; Martín, Carlos; Mora, Clara; Fatti, Gianluca; Antón, Alfonso

2017-08-01

To evaluate the accuracy of the macular retinal layer segmentation software of the Spectralis spectral-domain (SD) optical coherence tomography (OCT) device (Heidelberg Engineering, Inc., Heidelberg, Germany) to discriminate between healthy and early glaucoma (EG) eyes. Prospective, cross-sectional study. Forty EG eyes and 40 healthy controls were included. All participants were examined using the standard posterior pole and the peripapillary retinal nerve fiber layer (pRNFL) protocols of the Spectralis OCT device. Using an Early Treatment Diagnostic Retinopathy Study circle at the macular level, the automated retinal segmentation software was applied to determine thicknesses of the following parameters: total retinal thickness, inner retinal layer (IRL), macular retinal nerve fiber layer (mRNFL), macular ganglion cell layer (mGCL), macular inner plexiform layer (mIPL), macular inner nuclear layer (mINL), macular outer plexiform layer (mOPL), macular outer nuclear layer (mONL), photoreceptors (PR), and retinal pigmentary epithelium (RPE). The ganglion cell complex (GCC) was determined by adding the mRNFL, mGCL, and mIPL parameters and the ganglion cell layer-inner plexiform layer (mGCL-IPL) was determined by combining the mGCL and mIPL parameters. Thickness of each layer was compared between the groups, and the layer and sector with the best area under the receiver operating characteristic curve (AUC) were identified. Comparison of pRNFL, IRL, mRNFL, mGCL, mIPL, mGCC, mGCL-IPL, mINL, mOPL, mONL, PR, and RPE parameters and total retinal thicknesses between groups for the different areas and their corresponding AUCs. Peripapillary RNFL was significantly thinner in the EG group globally and in all 6 sectors assessed (P < 0.0005). For the macular variables, retinal thickness was significantly reduced in the EG group for total retinal thickness, mIRL, mRNFL, mGCL, and mIPL. The 2 best isolated parameters to discriminate between the 2 groups were pRNFL (AUC, 0.956) and mRNFL (AUC, 0.906). When mRNFL, mGCL, and mIPL measurements were combined (mGCC and mGCL plus mIPL), then its diagnostic performance improved (AUC, 0.940 and 0.952, respectively). Macular RNFL, mGCL-IPL, and mGCC measurements showed a high diagnostic capability to discriminate between healthy and EG participants. However, macular intraretinal measurements still have not overcome standard pRNFL parameters. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Retinal nerve fiber layer reflectance for early glaucoma diagnosis.

PubMed

Liu, Shuang; Wang, Bingqing; Yin, Biwei; Milner, Thomas E; Markey, Mia K; McKinnon, Stuart J; Rylander, Henry G

2014-01-01

Compare performance of normalized reflectance index (NRI) and retinal nerve fiber layer thickness (RNFLT) parameters determined from optical coherence tomography (OCT) images for glaucoma and glaucoma suspect diagnosis. Seventy-five eyes from 71 human subjects were studied: 33 controls, 24 glaucomatous, and 18 glaucoma-suspects. RNFLT and NRI maps were measured using 2 custom-built OCT systems and the commercial instrument RTVue. Using area under the receiver operating characteristic curve, RNFLT and NRI measured in 7 RNFL locations were analyzed to distinguish between control, glaucomatous, and glaucoma-suspect eyes. The mean NRI of the control group was significantly larger than the means of glaucomatous and glaucoma-suspect groups in most RNFL locations for all 3 OCT systems (P<0.05 for all comparisons). NRI performs significantly better than RNFLT at distinguishing between glaucoma-suspect and control eyes using RTVue OCT (P=0.008). The performances of NRI and RNFLT for classifying glaucoma-suspect versus control eyes were statistically indistinguishable for PS-OCT-EIA (P=0.101) and PS-OCT-DEC (P=0.227). The performances of NRI and RNFLT for classifying glaucomatous versus control eyes were statistically indistinguishable (PS-OCT-EIA: P=0.379; PS-OCT-DEC: P=0.338; RTVue OCT: P=0.877). NRI is a promising measure for distinguishing between glaucoma-suspect and control eyes and may indicate disease in the preperimetric stage. Results of this pilot clinical study warrant a larger study to confirm the diagnostic power of NRI for diagnosing preperimetric glaucoma.

Reproducibility of retinal nerve fiber layer thickness measures using eye tracking in children with nonglaucomatous optic neuropathy.

PubMed

Rajjoub, Raneem D; Trimboli-Heidler, Carmelina; Packer, Roger J; Avery, Robert A

2015-01-01

To determine the intra- and intervisit reproducibility of circumpapillary retinal nerve fiber layer (RNFL) thickness measures using eye tracking-assisted spectral-domain optical coherence tomography (SD OCT) in children with nonglaucomatous optic neuropathy. Prospective longitudinal study. Circumpapillary RNFL thickness measures were acquired with SD OCT using the eye-tracking feature at 2 separate study visits. Children with normal and abnormal vision (visual acuity ≥ 0.2 logMAR above normal and/or visual field loss) who demonstrated clinical and radiographic stability were enrolled. Intra- and intervisit reproducibility was calculated for the global average and 9 anatomic sectors by calculating the coefficient of variation and intraclass correlation coefficient. Forty-two subjects (median age 8.6 years, range 3.9-18.2 years) met inclusion criteria and contributed 62 study eyes. Both the abnormal and normal vision cohort demonstrated the lowest intravisit coefficient of variation for the global RNFL thickness. Intervisit reproducibility remained good for those with normal and abnormal vision, although small but statistically significant increases in the coefficient of variation were observed for multiple anatomic sectors in both cohorts. The magnitude of visual acuity loss was significantly associated with the global (ß = 0.026, P < .01) and temporal sector coefficient of variation (ß = 0.099, P < .01). SD OCT with eye tracking demonstrates highly reproducible RNFL thickness measures. Subjects with vision loss demonstrate greater intra- and intervisit variability than those with normal vision. Copyright © 2015 Elsevier Inc. All rights reserved.

Retina and Nerve Fiber Layer Thickness in Eyes with Thyroid-Associated Ophthalmopathy.

PubMed

Blum Meirovitch, Sharon; Leibovitch, Igal; Kesler, Anat; Varssano, David; Rosenblatt, Amir; Neudorfer, Meira

2017-05-01

Thyroid-associated ophthalmopathy (TAO) is an inflammatory disease that affects the thyroid gland and the eye orbit. Of patients with TAO, 3%-5% have severe sight-threatening disease due to optic neuropathy Optical coherence tomography (OCT), the non-invasive imaging technology that yields high-resolution cross-sectional images of the retina, provides qualitative and quantitative data on the retina. To apply this technique to quantitatively assess retinal nerve fiber layer (RNFL) and macular ring thicknesses in healthy subjects and in patients with TAO to determine their relationship to the severity of the orbital disease. All patients in the ophthalmology clinic who were diagnosed with TAO and underwent OCT imaging as part of their ocular examination comprised the study group, and healthy patients who volunteered to undergo OCT examination served as controls. Results of the complete ophthalmologic examination and OCT findings were collected from medical files, including the thickness of the RNFL and the macula. The study comprised 21 patients and 41 healthy controls. TAO patients exhibited RNFL thickening and inner macula thinning compared to healthy subjects. Mean RNFL thickness was correlated with the severity of the orbital disease. The OCT findings suggest that the retina is involved in TAO, probably as early as the subclinical stage. This highlights the ability of OCT to identify retinal changes earlier and far more accurately than is detected today, enabling earlier diagnosis and more timely treatment to prevent severe visual sequelae.

Correlation between glycemic control and peripapillary retinal nerve fiber layer thickness in Saudi type II diabetics

PubMed Central

Fahmy, Rania M; Bhat, Ramesa S; Al-Mutairi, Manar; Aljaser, Feda S; El-Ansary, Afaf

2018-01-01

Objective To evaluate the effect of diabetes mellitus (DM), diabetic retinopathy, and degree of glycemic control (glycosylated hemoglobin [HbA1c]) on peripapillary retinal nerve fiber layer thickness (RNFLT) using optical coherence tomography. Methods The study included 126 eyes of healthy controls (n=32) and diabetics patients (n=31), whose ages ranged from 40 to 70 years. The diabetic group was divided into: Subgroup 1: with HbA1c <7% and Subgroup 2: with HbA1c ≥7%. All patients underwent full ophthalmic examination. HbA1c level was obtained with the A1cNow+ system and the peripapillary RNFLT was measured using 3D-OCT 2000 Topcon (360-degree circular scan with 3.4 mm diameter centered on optic disc). Results The obtained data demonstrates significant decrease in peripapillary RNFLT in superior and inferior quadrants of the right eye (p=0.000 and p=0.039, respectively), and in superior quadrant of the left eye (p=0.002) with impairment of glycemic control. Pearson’s correlation test showed significant negative correlation of RNFLT with HbA1c in the superior quadrant in both eyes. Conclusion Impairment of glycemic control affects the peripapillary RNFLT mainly in the superior quadrant. This thickness also tends to decrease with long-standing DM, use of DM medications, and development of diabetic retinopathy. The measurement of peripapillary RNFLT may become a useful method to monitor early retinal changes in diabetic patients. PMID:29535499

Reproducibility of peripapillary retinal nerve fiber layer thickness with spectral domain cirrus high-definition optical coherence tomography in normal eyes.

PubMed

Hong, Samin; Kim, Chan Yun; Lee, Won Seok; Seong, Gong Je

2010-01-01

To assess the reproducibility of the new spectral domain Cirrus high-definition optical coherence tomography (HD-OCT; Carl Zeiss Meditec, Dublin, CA, USA) for analysis of peripapillary retinal nerve fiber layer (RNFL) thickness in healthy eyes. Thirty healthy Korean volunteers were enrolled. Three optic disc cube 200 x 200 Cirrus HD-OCT scans were taken on the same day in discontinuous sessions by the same operator without using the repeat scan function. The reproducibility of the calculated RNFL thickness and probability code were determined by the intraclass correlation coefficient (ICC), coefficient of variation (CV), test-retest variability, and Fleiss' generalized kappa (kappa). Thirty-six eyes were analyzed. For average RNFL thickness, the ICC was 0.970, CV was 2.38%, and test-retest variability was 4.5 microm. For all quadrants except the nasal, ICCs were 0.972 or higher and CVs were 4.26% or less. Overall test-retest variability ranged from 5.8 to 8.1 microm. The kappa value of probability codes for average RNFL thickness was 0.690. The kappa values of quadrants and clock-hour sectors were lower in the nasal areas than in other areas. The reproducibility of Cirrus HD-OCT to analyze peripapillary RNFL thickness in healthy eyes was excellent compared with the previous reports for time domain Stratus OCT. For the calculated RNFL thickness and probability code, variability was relatively higher in the nasal area, and more careful analyses are needed.

Ontogeny of the VIP system in the gastro-intestinal tract of the Axolotl, Ambystoma mexicanum: successive appearance of co-existing PACAP and NOS.

PubMed

Badawy, Gamal; Reinecke, Manfred

2003-03-01

Evidence for the presence and potential co-existence of vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP) and nitric oxide synthase (NOS) in gastro-intestinal endocrine cells and/or nerve fibers is conflicting and very few results exist on development. This immunofluorescence study aims to clarify the appearance and localization of VIP, PACAP and NOS in the gastro-intestinal tract of the Axolotl, Ambystoma mexicanum, during ontogeny. VIP-immunoreactivity appeared in nerve fibers as early as on day 3 after hatching likely indicating a particular role, such as a trophic action, of VIP in very early development. PACAP-immunoreactivity was observed 3 days later within the VIP-immunoreactive (-IR) fibers. From this time on, VIP- and PACAP-immunoreactivity exhibited complete co-existence. VIP/PACAP-IR fibers were found throughout the gastro-intestinal tract. They were most prominent in the myenteric plexus and the muscle layers and less frequent in the submucosa. NOS-immunoreactivity appeared as late as at the 1st (64 days) juvenile stage in a subpopulation of the VIP/PACAP-IR fibers that contacted submucosal arteries. We found only very few VIP/PACAP-IR perikarya, indicating that part of the VIP/PACAP-IR fibers is of extrinsic origin. On day 12 and in the 1st and 2nd (104 days) juvenile stage, infrequent PACAP-IR entero-endocrine cells were noted, while neither VIP- nor NOS-immunoreactivity occurred in endocrine cells at any stage of development. The complete coexistence of neuronal PACAP- and VIP-immunoreactivities and their very early appearance in ontogeny may suggest important and coordinated roles of both peptides in the control of Axolotl gastro-intestinal activity, while the VIP/ PACAP/NOS-IR fibers may be involved in the regulation of submucosal blood flow.

Localization of cholinergic innervation and neurturin receptors in adult mouse heart and expression of the neurturin gene.

PubMed

Mabe, Abigail M; Hoard, Jennifer L; Duffourc, Michelle M; Hoover, Donald B

2006-10-01

Neurturin (NRTN) is a neurotrophic factor required during development for normal cholinergic innervation of the heart, but whether NRTN continues to function in the adult heart is unknown. We have therefore evaluated NRTN expression in adult mouse heart and the association of NRTN receptors with intracardiac cholinergic neurons and nerve fibers. Mapping the regional distribution and density of cholinergic nerves in mouse heart was an integral part of this goal. Analysis of RNA from adult C57BL/6 mouse hearts demonstrated NRTN expression in atrial and ventricular tissue. Virtually all neurons in the cardiac parasympathetic ganglia exhibited the cholinergic phenotype, and over 90% of these cells contained both components of the NRTN receptor, Ret tyrosine kinase and GDNF family receptor alpha2 (GFRalpha2). Cholinergic nerve fibers, identified by labeling for the high affinity choline transporter, were abundant in the sinus and atrioventricular nodes, ventricular conducting system, interatrial septum, and much of the right atrium, but less abundant in the left atrium. The right ventricular myocardium contained a low density of cholinergic nerves, which were sparse in other regions of the working ventricular myocardium. Some cholinergic nerves were also associated with coronary vessels. GFRalpha2 was present in most cholinergic nerve fibers and in Schwann cells and their processes throughout the heart. Some cholinergic nerve fibers, such as those in the sinus node, also exhibited Ret immunoreactivity. These findings provide the first detailed mapping of cholinergic nerves in mouse heart and suggest that the neurotrophic influence of NRTN on cardiac cholinergic innervation continues in mature animals.

In vivo laser confocal microscopy of Bowman's layer of the cornea.

PubMed

Kobayashi, Akira; Yokogawa, Hideaki; Sugiyama, Kazuhisa

2006-12-01

To investigate in vivo microstructures of Bowman's layer in normal human subjects using a cornea-specific in vivo laser scanning confocal microscope (Heidelberg Retina Tomograph 2 Rostock Cornea Module, HRT2-RCM). Single-center, prospective, observational case series. Nineteen normal volunteers (10 male, 9 female; mean age, 46.2+/-21.7 years [range, 18-77]). The central and peripheral cornea, specifically the epithelium, Bowman's layer, and its subjacent stroma, were examined using the HRT2-RCM. Selected images of the corneal layers were evaluated qualitatively for the shape and degree of light reflection of the microstructures. In all subjects, normal epithelial (superficial, wing, basal) cells, subbasal nerve plexus, Bowman's layer, and its subjacent stoma were observed clearly. However, in all subjects, polymorphic structures composed of fibrillar materials with less reflectivity than corneal nerves were observed beneath Bowman's layer. After application of pressure by a Tomo-cap, we observed numerous ridges that protruded into the epithelial basal and wing cell layers. Superficial stromal striae were also observed. These ridges and striae corresponded exactly to the orientation of the fibrous structures located beneath the epithelial cells. We report for the first time, the presence of polymorphic structures composed of fibrillar materials (K-structures) beneath Bowman's layer in normal human subjects, detected by HRT2-RCM. We surmise that these microstructures may correspond to the modified and condensed anterior stromal collagen fibers/lamellae that merge into Bowman's layer and that these fibrillar materials may be responsible for the formation of the anterior corneal mosaic. Further investigation of these microstructures in diseased eyes may provide insights into their pathophysiologic role in Bowman's layer.

Challenges for Nerve Repair Using Chitosan-Siloxane Hybrid Porous Scaffolds

PubMed Central

Shirosaki, Yuki; Hayakawa, Satoshi; Osaka, Akiyoshi; Lopes, Maria A.; Santos, José D.; Geuna, Stefano; Mauricio, Ana C.

2014-01-01

The treatment of peripheral nerve injuries remains one of the greatest challenges of neurosurgery, as functional recover is rarely satisfactory in these patients. Recently, biodegradable nerve guides have shown great potential for enhancing nerve regeneration. A major advantage of these nerve guides is that no foreign material remains after the device has fulfilled its task, which spares a second surgical intervention. Recently, we studied peripheral nerve regeneration using chitosan-γ-glycidoxypropyltrimethoxysilane (chitosan-GPTMS) porous hybrid membranes. In our studies, these porous membranes significantly improved nerve fiber regeneration and functional recovery in rat models of axonotmetic and neurotmetic sciatic nerve injuries. In particular, the number of regenerated myelinated nerve fibers and myelin thickness were significantly higher in rat treated with chitosan porous hybrid membranes, whether or not they were used in combination with mesenchymal stem cells isolated from the Wharton's jelly of the umbilical cord. In this review, we describe our findings on the use of chitosan-GPTMS hybrids for nerve regeneration. PMID:25054129

Early changes in muscle atrophy and muscle fiber type conversion after spinal cord transection and peripheral nerve transection in rats.

PubMed

Higashino, Kosaku; Matsuura, Tetsuya; Suganuma, Katsuyoshi; Yukata, Kiminori; Nishisho, Toshihiko; Yasui, Natsuo

2013-05-20

Spinal cord transection and peripheral nerve transection cause muscle atrophy and muscle fiber type conversion. It is still unknown how spinal cord transection and peripheral nerve transection each affect the differentiation of muscle fiber type conversion mechanism and muscle atrophy. The aim of our study was to evaluate the difference of muscle weight change, muscle fiber type conversion, and Peroxisome proliferator-activated receptor-γ coactivatior-1α (PGC-1α) expression brought about by spinal cord transection and by peripheral nerve transection. Twenty-four Wistar rats underwent surgery, the control rats underwent a laminectomy; the spinal cord injury group underwent a spinal cord transection; the denervation group underwent a sciatic nerve transection. The rats were harvested of the soleus muscle and the TA muscle at 0 week, 1 week and 2 weeks after surgery. Histological examination was assessed using hematoxylin and eosin (H&E) staining and immunofluorescent staing. Western blot was performed with 3 groups. Both sciatic nerve transection and spinal cord transection caused muscle atrophy with the effect being more severe after sciatic nerve transection. Spinal cord transection caused a reduction in the expression of both sMHC protein and PGC-1α protein in the soleus muscle. On the other hand, sciatic nerve transection produced an increase in expression of sMHC protein and PGC-1α protein in the soleus muscle. The results of the expression of PGC-1α were expected in other words muscle atrophy after sciatic nerve transection is less than after spinal cord transection, however muscle atrophy after sciatic nerve transection was more severe than after spinal cord transection. In the conclusion, spinal cord transection diminished the expression of sMHC protein and PGC-1α protein in the soleus muscle. On the other hand, sciatic nerve transection enhanced the expression of sMHC protein and PGC-1α protein in the soleus muscle.

GLUT-3 expression in human skeletal muscle

NASA Technical Reports Server (NTRS)

Stuart, C. A.; Wen, G.; Peng, B. H.; Popov, V. L.; Hudnall, S. D.; Campbell, G. A.

2000-01-01

Muscle biopsy homogenates contain GLUT-3 mRNA and protein. Before these studies, it was unclear where GLUT-3 was located in muscle tissue. In situ hybridization using a midmolecule probe demonstrated GLUT-3 within all muscle fibers. Fluorescent-tagged antibody reacting with affinity-purified antibody directed at the carboxy-terminus demonstrated GLUT-3 protein in all fibers. Slow-twitch muscle fibers, identified by NADH-tetrazolium reductase staining, possessed more GLUT-3 protein than fast-twitch fibers. Electron microscopy using affinity-purified primary antibody and gold particle-tagged second antibody showed that the majority of GLUT-3 was in association with triads and transverse tubules inside the fiber. Strong GLUT-3 signals were seen in association with the few nerves that traversed muscle sections. Electron microscopic evaluation of human peripheral nerve demonstrated GLUT-3 within the axon, with many of the particles related to mitochondria. GLUT-3 protein was found in myelin but not in Schwann cells. GLUT-1 protein was not present in nerve cells, axons, myelin, or Schwann cells but was seen at the surface of the peripheral nerve in the perineurium. These studies demonstrated that GLUT-3 mRNA and protein are expressed throughout normal human skeletal muscle, but the protein is predominantly found in the triads of slow-twitch muscle fibers.

Effect of improper scan alignment on retinal nerve fiber layer thickness measurements using Stratus optical coherence tomograph.

PubMed

Vizzeri, Gianmarco; Bowd, Christopher; Medeiros, Felipe A; Weinreb, Robert N; Zangwill, Linda M

2008-08-01

Misalignment of the Stratus optical coherence tomograph scan circle placed by the operator around the optic nerve head (ONH) during each retinal nerve fiber layer (RNFL) examination can affect the instrument reproducibility and its theoretical ability to detect true structural changes in the RNFL thickness over time. We evaluated the effect of scan circle placement on RNFL measurements. Observational clinical study. Sixteen eyes of 8 normal participants were examined using the Stratus optical coherence tomograph Fast RNFL thickness acquisition protocol (software version 4.0.7; Carl Zeiss Meditec, Dublin, CA). Four consecutive images were taken by the same operator with the circular scan centered on the optic nerve head. Four images each with the scan displaced superiorly, inferiorly, temporally, and nasally were also acquired. Differences in average and sectoral RNFL thicknesses were determined. For the centered scans, the coefficients of variation (CV) and the intraclass correlation coefficient for the average RNFL thickness measured were calculated. When the average RNFL thickness of the centered scans was compared with the average RNFL thickness of the displaced scans individually using analysis of variance with post-hoc analysis, no difference was found between the average RNFL thickness of the nasally (105.2 microm), superiorly (106.2 microm), or inferiorly (104.1 microm) displaced scans and the centered scans (106.4 microm). However, a significant difference (analysis of variance with Dunnett's test: F=8.82, P<0.0001) was found between temporally displaced scans (115.8 microm) and centered scans. Significant differences in sectoral RNFL thickness measurements were found between centered and each displaced scan. The coefficient of variation for average RNFL thickness was 1.75% and intraclass correlation coefficient was 0.95. In normal eyes, average RNFL thickness measurements are robust and similar with significant superior, inferior, and nasal scan displacement, but average RNFL thickness is greater when scans are displaced temporally. Parapapillary scan misalignment produces significant changes in RNFL assessment characterized by an increase in measured RNFL thickness in the quadrant in which the scan is closer to the disc, and a significant decrease in RNFL thickness in the quadrant in which the scan is displaced further from the optic disc.

Proteomic profiling reveals crucial retinal protein alterations in the early phase of an experimental glaucoma model.

PubMed

Anders, Fabian; Teister, Julia; Funke, Sebstian; Pfeiffer, Norbert; Grus, Franz; Solon, Thanos; Prokosch, Verena

2017-07-01

Clinical glaucoma is difficult to assess in terms of molecular pathophysiology, prompting studies in experimental models of glaucoma. The purpose of this study was to investigate quantitative changes in retinal protein expression at the onset of experimental glaucoma in rats. Analyzing the proteome provides a suitable tool to decipher the pathophysiological processes in glaucomatous degeneration. Thermic cauterization of episcleral veins was utilized to elevate the intraocular pressure in Sprague Dawley rats. Morphological changes were surveyed on a cellular level with a staining of Brn3a-positive cells. The retinal nerve fiber layer was investigated using optical coherence tomography (OCT, Heidelberg Engineering) and the optic nerve was analyzed by an axonal grading system. Mass spectrometry-featured quantitative proteomics and immunohistochemical staining was used to identify specifically altered proteins in the course of intraocular pressure elevation and initial neurodegeneration. Proteomic data were further analyzed with Ingenuity Pathway Analysis and Cytoscape to analyze further molecular associations. The intraocular pressure rose significantly (p < 0.001) for the follow-up period of 3 weeks after which animals were sacrificed. Eyes exposed to an elevated intraocular pressure showed an initial decrease of retinal ganglion cells, retinal nerve fiber layer (p < 0.05) and an impairment of the optic nerve (p < 0.01). Mass spectrometry led to the identification and quantification of 931 retinal proteins, whereas 32 were considerably altered. Bioinformatics-assisted clustering revealed that a majority of these proteins are functionally associated with cell differentiation, apoptosis and stress response. The creation of an interactive protein network showed that numerous altered proteins are connected regarding their cellular function. Protein kinase b, mitogen-activated protein kinase 1 and the NF-κB complex seem to be essential molecules in this context. In conclusion, these results provide further lines of evidence that substantial molecular changes occur at the onset of the disease, identifying potential key players, which might be useful as biomarkers for diagnostics and development of medical treatment in the future.

Reflex effects on components of synchronized renal sympathetic nerve activity.

PubMed

DiBona, G F; Jones, S Y

1998-09-01

The effects of peripheral thermal receptor stimulation (tail in hot water, n = 8, anesthetized) and cardiac baroreceptor stimulation (volume loading, n = 8, conscious) on components of synchronized renal sympathetic nerve activity (RSNA) were examined in rats. The peak height and peak frequency of synchronized RSNA were determined. The renal sympathoexcitatory response to peripheral thermal receptor stimulation was associated with an increase in the peak height. The renal sympathoinhibitory response to cardiac baroreceptor stimulation was associated with a decrease in the peak height. Although heart rate was significantly increased with peripheral thermal receptor stimulation and significantly decreased with cardiac baroreceptor stimulation, peak frequency was unchanged. As peak height reflects the number of active fibers, reflex increases and decreases in synchronized RSNA are mediated by parallel increases and decreases in the number of active renal nerve fibers rather than changes in the centrally based rhythm or peak frequency. The increase in the number of active renal nerve fibers produced by peripheral thermal receptor stimulation reflects the engagement of a unique group of silent renal sympathetic nerve fibers with a characteristic response pattern to stimulation of arterial baroreceptors, peripheral and central chemoreceptors, and peripheral thermal receptors.

On the nature of the afferent fibers of oculomotor nerve.

PubMed

Manni, E; Draicchio, F; Pettorossi, V E; Carobi, C; Grassi, S; Bortolami, R; Lucchi, M L

1989-03-01

The oculogyric nerves contain afferent fibers originating from the ophthalmic territory, the somata of which are located in the ipsilateral semilunar ganglion. These primary sensory neurons project to the Subnucleus Gelatinosus of the Nucleus Caudalis Trigemini, where they make presynaptic contact with the central endings of the primary trigeminal afferents running in the fifth cranial nerve. After complete section of the trigeminal root, the antidromic volleys elicited in the trunk of the third cranial nerve by stimulating SG of NCT consisted of two waves belonging to the A delta and C groups. The area of both components of the antidromic volleys decreased both after bradykinin and hystamine injection into the corresponding cutaneous region and after thermic stimulation of the ipsilateral trigeminal ophthalmic territory. The reduction of such potentials can be explained in terms of collision between the antidromic volleys and those elicited orthodromically by chemical and thermic stimulation. Also, capsaicin applied on the nerve induced an immediate increase, followed by a long lasting decrease, of orthodromic evoked response area. These findings bring further support to the nociceptive nature of the afferent fibers running into the oculomotor nerve.

Sox10 Expression in Goldfish Retina and Optic Nerve Head in Controls and after the Application of Two Different Lesion Paradigms

PubMed Central

Parrilla, Marta; León-Lobera, Fernando; Lillo, Concepción; Arévalo, Rosario; Aijón, José; Lara, Juan Manuel; Velasco, Almudena

2016-01-01

The mammalian central nervous system (CNS) is unable to regenerate. In contrast, the CNS of fish, including the visual system, is able to regenerate after damage. Moreover, the fish visual system grows continuously throughout the life of the animal, and it is therefore an excellent model to analyze processes of myelination and re-myelination after an injury. Here we analyze Sox10+ oligodendrocytes in the goldfish retina and optic nerve in controls and after two kinds of injuries: cryolesion of the peripheral growing zone and crushing of the optic nerve. We also analyze changes in a major component of myelin, myelin basic protein (MBP), as a marker for myelinated axons. Our results show that Sox10+ oligodendrocytes are located in the retinal nerve fiber layer and along the whole length of the optic nerve. MBP was found to occupy a similar location, although its loose appearance in the retina differed from the highly organized MBP+ axon bundles in the optic nerve. After optic nerve crushing, the number of Sox10+ cells decreased in the crushed area and in the optic nerve head. Consistent with this, myelination was highly reduced in both areas. In contrast, after cryolesion we did not find changes in the Sox10+ population, although we did detect some MBP- degenerating areas. We show that these modifications in Sox10+ oligodendrocytes are consistent with their role in oligodendrocyte identity, maintenance and survival, and we propose the optic nerve head as an excellent area for research aimed at better understanding of de- and remyelination processes. PMID:27149509

The morphological substrate for Renal Denervation: Nerve distribution patterns and parasympathetic nerves. A post-mortem histological study.

PubMed

van Amsterdam, Wouter A C; Blankestijn, Peter J; Goldschmeding, Roel; Bleys, Ronald L A W

2016-03-01

Renal Denervation as a possible treatment for hypertension has been studied extensively, but knowledge on the distribution of nerves surrounding the renal artery is still incomplete. While sympathetic and sensory nerves have been demonstrated, there is no mention of the presence of parasympathetic nerve fibers. To provide a description of the distribution patterns of the renal nerves in man, and, in addition, provide a detailed representation of the relative contribution of the sympathetic, parasympathetic and afferent divisions of the autonomic nervous system. Renal arteries of human cadavers were each divided into four longitudinal segments and immunohistochemically stained with specific markers for afferent, parasympathetic and sympathetic nerves. Nerve fibers were semi-automatically quantified by computerized image analysis, and expressed as cross-sectional area relative to the distance to the lumen. A total of 3372 nerve segments were identified in 8 arteries of 7 cadavers. Sympathetic, parasympathetic and afferent nerves contributed for 73.5% (95% CI: 65.4-81.5%), 17.9% (10.7-25.1%) and 8.7% (5.0-12.3%) of the total cross-sectional nerve area, respectively. Nerves are closer to the lumen in more distal segments and larger bundles that presumably innervate the kidney lie at 1-3.5mm distance from the lumen. The tissue-penetration depth of the ablation required to destroy 50% of the nerve fibers is 2.37 mm in the proximal segment and 1.78 mm in the most distal segments. Sympathetic, parasympathetic and afferent nerves exist in the vicinity of the renal artery. The results warrant further investigation of the role of the parasympathetic nervous system on renal physiology, and may contribute to refinement of the procedure by focusing the ablation on the most distal segment. Copyright © 2015 Elsevier GmbH. All rights reserved.

CHANGES IN CHOROIDAL THICKNESS IN AND OUTSIDE THE MACULA AFTER HEMODIALYSIS IN PATIENTS WITH END-STAGE RENAL DISEASE

PubMed Central

Chang, In Boem; Lee, Jeong Hyun

2017-01-01

Purpose: To evaluate changes in choroidal thickness in and outside the macula as a result of hemodialysis (HD) in patients with end-stage renal disease. Methods: Patients with end-stage renal disease treated with maintenance HD in the Dialysis Unit of Sanggye Paik Hospital, Seoul, South Korea, were included in this study. The choroidal thickness was measured in and outside the macula before and after HD (paired t-test). Choroidal thickness in the macula was measured at the foveal center and 1.5 mm temporal to the foveal center and outside the macula was measured at superior, inferior, and nasal area 3.5 mm from the optic disk margin. Peripapillary retinal nerve fiber layer thickness, intraocular pressure, central corneal thickness, and systemic parameters such as serum osmolarity and blood pressure (BP) were measured before and after HD (paired t-test). We divided patients into two groups, diabetic and nondiabetic groups to compare the changes in choroidal thickness. Patients with diabetes were subdivided into two groups: severe retinal change group and moderate retinal change group (Mann–Whitney test). Pearson's correlation test was used to evaluate the correlations between choroidal thickness and changes in serum osmolarity, BP, and body weight loss. Choroidal thickness and peripapillary retinal nerve fiber layer thickness were measured using spectral-domain optical coherence tomography. Results: Fifty-four eyes of 31 patients with end-stage renal disease were included. After HD, the mean intraocular pressure was significantly decreased from 14.8 ± 2.5 mmHg to 13.0 ± 2.6 mmHg (P < 0.001). Choroidal thickness was reduced in all areas (P < 0.001). The reduction in choroidal thickness correlated with body weight loss, decrease in serum osmolarity, and decrease in systolic BP (P < 0.05). In the diabetic group, the mean choroidal thickness changes were greater than those in the nondiabetic group (P < 0.05). The severe retinal change group showed greater changes in choroidal thickness in all areas (P < 0.05). Other factors that significantly decreased after HD included serum osmolarity, body weight, and systolic BP (all P < 0.001). The diabetic group showed greater changes in serum osmolarity and body weight (P < 0.001, P = 0.048, respectively). The measured overall changes in peripapillary retinal nerve fiber layer thickness or central corneal thickness were not statistically significant. Conclusion: Changes in body weight, serum osmolarity, and BP during HD may affect choroidal thickness in and outside the macula. PMID:27557086

Risk of Visual Field Progression in Glaucoma Patients with Progressive Retinal Nerve Fiber Layer Thinning: A 5-Year Prospective Study.

PubMed

Yu, Marco; Lin, Chen; Weinreb, Robert N; Lai, Gilda; Chiu, Vivian; Leung, Christopher Kai-Shun

2016-06-01

To investigate whether progressive retinal nerve fiber layer (RNFL) thinning is predictive of progressive visual field (VF) loss in glaucoma. Prospective study. A total of 139 primary open-angle glaucoma patients (240 eyes) followed up for ≥5 years. Retinal nerve fiber layer imaging and VF testing were performed at ∼4-month intervals. Progressive RNFL thinning was determined by event analysis (Guided Progression Analysis [GPA]) and trend analysis (Trend-based Progression Analysis [TPA]) of serial registered RNFL thickness maps. VF progression was detected according to the Early Manifest Glaucoma Trial (EMGT) ("likely progression") and pointwise linear regression (PLR) criteria (≥3 contiguous locations with sensitivity change <0 decibels [dB]/year at P < 0.01). Hazard ratios (HRs) for predicting VF progression were calculated by Cox proportional hazard modeling with progressive RNFL thinning as a time-dependent covariate. The specificity of GPA/TPA for detection of RNFL changes was determined by the proportion of eyes with significant RNFL thinning/thickening in 25 normal subjects followed weekly for 8 consecutive weeks and the proportion with significant RNFL thickening in the glaucoma group. The HRs of VF progression. A total of 65 (27.1%) and 117 eyes (48.8%) had progressive RNFL thinning based on GPA and TPA, respectively, and 30 (12.5%) and 39 eyes (16.3%) had VF progression per the EMGT and PLR criteria, respectively, during follow-up. Eyes with progressive RNFL thinning had lower VF survival estimates and a faster decline of visual field index than eyes without. Progressive RNFL thinning predicted the development of VF progression with HRs of 8.44 (95% confidence interval, 3.30-21.61) (EMGT criteria) and 5.11 (2.51-10.42) (PLR criteria) for TPA and 3.95 (1.74-8.93) (EMGT criteria) and 3.81 (1.83-7.92) (PLR criteria) for GPA after controlling for baseline covariates. The specificities of GPA and TPA were 100% (83.4%-100.0%) in the normal group and 81.7% (76.2%-86.4%) and 84.2% (78.9%-88.6%), respectively, in the glaucoma group. Progressive RNFL thinning determined by GPA and TPA is predictive of detectable functional decline in glaucoma. This finding underscores the significance of detecting progressive RNFL thinning and its relevance to initiate or augment treatment for glaucoma patients. Regulatory authorities may consider progressive RNFL thinning as an outcome measure in clinical trials for evaluation of glaucoma treatment. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Electrophysiologic alterations in the excitability of the sciatic and vagus nerves during early stages of sepsis.

PubMed

Diniz, Lúcio Ricardo Leite; Portella, Viviane Gomes; da Silva Alves, Kerly Shamira; Araújo, Pâmella Cristina da Costa; de Albuquerque Júnior, Ricardo Luiz Cavalcanti; Cavalcante de Albuquerque, Aline Alice; Coelho-de-Souza, Andrelina Noronha; Leal-Cardoso, José Henrique

2018-01-01

Nonspecific and delayed diagnosis of neurologic damage contributes to the development of neuropathies in patients with severe sepsis. The present study assessed the electrophysiologic parameters related to the excitability and conductibility of sciatic and vagus nerves during early stages of sepsis. Twenty-four hours after sepsis induced by cecal ligation and puncture (CLP) model, sciatic and vagus nerves of septic (CLP group) and control (sham group) rats were removed, and selected electric stimulations were applied to measure the parameters of the first and second components of the compound action potential. The first component originated from fibers with motor and sensory functions (Types A α and A β fibers) with a large conduction velocity (70-120 m/s), and the second component originated from fibers (Type A γ ) with sensorial function. To evaluate the presence of sensorial alterations, the sensitivity to non-noxious mechanical stimuli was measured by using the von Frey test. Hematoxylin and eosin staining of the nerves was performed. We observed an increase of rheobase followed by a decrease in the first component amplitude and a higher paw withdrawal threshold in response to the application of von Frey filaments in sciatic nerves from the CLP group compared to the sham group. Differently, a decrease in rheobase and an increase in the first component amplitude of vagal C fibers from CLP group were registered. No significant morphologic alteration was observed. Our data showed that the electrophysiologic alterations in peripheral nerves vary with the fiber type and might be identified in the first 24 h of sepsis, before clinical signs of neuromuscular disorders.

Microneurography in rats: a minimally invasive method to record single C-fiber action potentials from peripheral nerves in vivo.

PubMed

Serra, Jordi; Bostock, Hugh; Navarro, Xavier

2010-02-19

Microneurography is a method suitable for recording intraneural single or multiunit action potentials in conscious subjects. Microneurography has rarely been applied to animal experiments, where more invasive methods, like the teased fiber recording technique, are widely used. We have tested the feasibility of microneurographic recordings from the peripheral nerves of rats. Tungsten microelectrodes were inserted into the sciatic nerve at mid-thigh level. Single or multiunit action potentials evoked by regular electrical stimulation were recorded, digitized and displayed as a raster plot of latencies. The method allows unambiguous recording and recognition of single C-fiber action potentials from an in vivo preparation, with minimal disruption of the nerve being recorded. Multiple C-fibers can be recorded simultaneously for several hours, and if the animal is allowed to recover, repeated recording sessions can be obtained from the same nerve at the same level over a period of weeks or months. Also, single C units can be functionally identified by their changes in latency to natural stimuli, and insensitive units can be recognized as 'silent' nociceptors or sympathetic efferents by their distinctive profiles of activity-dependent slowing during repetitive electrical stimulation, or by the effect on spontaneous efferent activity of a proximal anesthetic block. Moreover, information about the biophysical properties of C axons can be obtained from their latency recovery cycles. Finally, we show that this preparation is potentially suitable for the study of C-fiber behavior in models of neuropathies and nerve lesions, both under resting conditions and in response to drug administration.

Comparing the Rates of Retinal Nerve Fiber Layer and Ganglion Cell-Inner Plexiform Layer Loss in Healthy Eyes and in Glaucoma Eyes.

PubMed

Hammel, Naama; Belghith, Akram; Weinreb, Robert N; Medeiros, Felipe A; Mendoza, Nadia; Zangwill, Linda M

2017-06-01

To compare the rates of circumpapillary retinal nerve fiber layer (RNFL) and macular retinal ganglion cell-inner plexiform layer (GCIPL) change over time in healthy and glaucoma eyes. Cohort study. The rates of circumpapillary RNFL and macular GCIPL loss in 28 healthy subjects and 97 glaucoma subjects from the Diagnostic Innovations in Glaucoma Study (DIGS) were compared using mixed-effects models. The median follow-up time and number of visits were 1.7 years and 6 visits and 3.2 years and 7 visits for healthy and glaucoma eyes, respectively. Significant rates of loss of both global circumpapillary RNFL and average macular GCIPL thickness were detectable in early and moderate glaucoma eyes; in severe glaucoma eyes, rates of average macular GCIPL loss were significant, but rates of global circumpapillary RNFL loss were not. In glaucoma eyes, mean rates of global circumpapillary RNFL thickness change (-0.98 μm/year [95% confidence interval (CI), -1.20 to -0.76]) and normalized global circumpapillary RNFL change (-1.7%/year [95% CI, -2.1 to -1.3]) were significantly faster than average macular GCIPL change (-0.57 μm/year [(95% CI, -0.73 to -0.41]) and normalized macular GCIPL change (-1.3%/year [95% CI, -1.7 to -0.9]). The rates of global and inferior RNFL change were weakly correlated with global and inferior macular GCIPL change (r ranges from 0.16 to 0.23, all P < .05). In this cohort, the rate of circumpapillary RNFL thickness change was faster than macular GCIPL change for glaucoma eyes. Global circumpapillary RNFL thickness loss was detectable in early and moderate glaucoma, and average macular GCIPL thickness loss was detectable in early, moderate, and severe glaucoma, suggesting that structural changes can be detected in severe glaucoma. Copyright © 2017 Elsevier Inc. All rights reserved.

Peripheral choline acetyltransferase in rat skin demonstrated by immunohistochemistry.

PubMed

Hanada, Keiji; Kishimoto, Saburo; Bellier, Jean-Pierre; Kimura, Hiroshi

2013-03-01

Conventional choline acetyltransferase immunohistochemistry has been used widely for visualizing central cholinergic neurons and fibers but not often for labeling peripheral structures, probably because of their poor staining. The recent identification of the peripheral type of choline acetyltransferase (pChAT) has enabled the clear immunohistochemical detection of many known peripheral cholinergic elements. Here, we report the presence of pChAT-immunoreactive nerve fibers in rat skin. Intensely stained nerve fibers were distributed in association with eccrine sweat glands, blood vessels, hair follicles and portions just beneath the epidermis. These results suggest that pChAT-positive nerves participate in the sympathetic cholinergic innervation of eccrine sweat glands. Moreover, pChAT also appears to play a role in cutaneous sensory nerve endings. These findings are supported by the presence of many pChAT-positive neuronal cells in the sympathetic ganglion and dorsal root ganglion. Thus, pChAT immunohistochemistry should provide a novel and unique tool for studying cholinergic nerves in the skin.

Phenotyping sensory nerve endings in vitro in the mouse

PubMed Central

Zimmermann, Katharina; Hein, Alexander; Hager, Ulrich; Kaczmarek, Jan Stefan; Turnquist, Brian P; Clapham, David E; Reeh, Peter W

2014-01-01

This protocol details methods to identify and record from cutaneous primary afferent axons in an isolated mammalian skin–saphenous nerve preparation. The method is based on extracellular recordings of propagated action potentials from single-fiber receptive fields. Cutaneous nerve endings show graded sensitivities to various stimulus modalities that are quantified by adequate and controlled stimulation of the superfused skin with heat, cold, touch, constant punctate pressure or chemicals. Responses recorded from single-fibers are comparable with those obtained in previous in vivo experiments on the same species. We describe the components and the setting-up of the basic equipment of a skin–nerve recording station (few days), the preparation of the skin and the adherent saphenous nerve in the mouse (15–45 min) and the isolation and recording of neurons (approximately 1–3 h per recording). In addition, stimulation techniques, protocols to achieve single-fiber recordings, issues of data acquisition and action potential discrimination are discussed in detail. PMID:19180088

Palisade endings are present in canine extraocular muscles and have a cholinergic phenotype

PubMed Central

RUNGALDIER, Stefanie; POMIKAL, Christine; STREICHER, Johannes; BLUMER, Roland

2016-01-01

Classical proprioceptors, like Golgi tendon organs and muscle spindles are absent in the extraocular muscles (EOMs) of most mammals. Instead, a nerve end organ was detected in the EOMs of each species including sheep, cats, rabbits, rats, monkeys, and man examined so far: the palisade ending. Until now no evidence appeared that palisade endings are present in canine EOMs. We analyzed dog EOMs by confocal laser scanning microscopy, 3D reconstruction, and transmission electron microscopy. In EOM wholemount preparations stained with antibodies against neurofilament and synaptophysin we found typical palisade endings. Nerve fibers coming from the muscle extended into the tendon. There, the nerve fibers turned 180° and returned to branch into preterminal axons which established nerve terminals around a single muscle fiber tip. Fine structural analyses revealed that each palisade ending in dog EOMs established nerve terminals on the tendon. In some palisade endings we found nerve terminals contacting the muscle fiber as well. Such neuromuscular contacts had a basal lamina in the synaptic cleft thereby resembling motor terminals. By using antibodies against choline acetyltransferase (ChAT) we proved that canine palisade endings are ChAT-immunoreactive. This study shows that palisade endings are present in canine EOMs. In line with prior findings in cat and monkey, palisade endings in dog have a cholinergic phenotype. PMID:19766165

Axonal loss from acute optic neuropathy documented by scanning laser polarimetry

PubMed Central

Meier, F M; Bernasconi, P; Stürmer, J; Caubergh, M-J; Landau, K

2002-01-01

Background/aims: Retinal nerve fibre layer analysis by scanning laser polarimetry has been shown to facilitate diagnosis of glaucoma while its role in glaucoma follow up is still unclear. A major difficulty is the slow reduction of retinal nerve fibre layer thickness in glaucomatous optic neuropathy. Eyes of patients were studied after acute retrobulbar optic nerve lesion in order to evaluate the usefulness of scanning laser polarimetry in documenting retinal nerve fibre layer loss over time. Methods: Five patients who suffered severe retrobulbar optic neuropathy have had repeated measurements of the retinal nerve fibre layer using scanning laser polarimetry at various intervals, the first examination being within 1 week of injury. Results: All eyes showed a marked decrease in peripapillary retinal nerve fibre layer thickness, which followed an exponential curve and occurred predominantly within 8 weeks of injury. Compared to a previous study using red-free photographs, scanning laser polarimetry showed retinal nerve fibre layer loss earlier in the course of descending atrophy. Conclusion: Scanning laser polarimetry is useful for early detection and documentation of retinal nerve fibre layer loss following acute injury to the retrobulbar optic nerve. It seems to be a promising tool for follow up of individual glaucoma patients. PMID:11864884

Effectiveness of fibrin adhesive in facial nerve anastomosis in dogs compared with standard microsuturing technique.

PubMed

Attar, Bijan Movahedian; Zalzali, Haidar; Razavi, Mohammad; Ghoreishian, Mehdi; Rezaei, Majid

2012-10-01

Epineural suturing is the most common technique used for peripheral nerve anastomosis. In addition to the foreign body reaction to the suture material, the surgical duration and difficulty of suturing in confined anatomic locations are major problems. We evaluated the effectiveness of fibrin glue as an acceptable alternative for nerve anastomosis in dogs. Eight adult female dogs weighing 18 to 24 kg were used in the present study. The facial nerve was transected bilaterally. On the right side, the facial nerve was subjected to epineural suturing; and on the left side, the nerve was anastomosed using fibrin adhesive. After 16 weeks, the nerve conduction velocity and proportion of the nerve fibers that crossed the anastomosis site were evaluated and compared for the epineural suture (right side) and fibrin glue (left side). The data were analyzed using the paired t test and univariate analysis of variance. The mean postoperative nerve conduction velocity was 29.87 ± 7.65 m/s and 26.75 ± 3.97 m/s on the right and left side, respectively. No statistically significant difference was found in the postoperative nerve conduction velocity between the 2 techniques (P = .444). The proportion of nerve fibers that crossed the anastomotic site was 71.25% ± 7.59% and 72.25% ± 8.31% on the right and left side, respectively. The histologic evaluation showed no statistically significant difference in the proportion of the nerve fibers that crossed the anastomotic site between the 2 techniques (P = .598). The results suggest that the efficacies of epineural suturing and fibrin gluing in peripheral nerve anastomosis are similar. Copyright © 2012 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

The primary vestibular projection to the cerebellar cortex in the pigeon (Columba livia)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schwarz, I.E.; Schwarz, D.W.

1983-06-01

The cerebellar cortex of the pigeon receiving direct vestibular afferents was delineated by anterograde transport of (/sup 3/H)-amino acids injected into the vestibular nerve. Labelled mossy fiber rosettes in the granular layer were concentrated in lobule X (nodulus) and to a lesser extent, in the ventral portion of lobule IXd (uvula and paraflocculus). A few solitary labelled rosettes were also found in more dorsal portions of lobule IX, as well as in the anterior lobe between lobule II and IV. The lingula remained unlabelled. Discrete injections of (/sup 3/H)-leucine into the cristae of each of the three semicircular canals ormore » the utricular macula yielded a similar distribution of fewer labelled rosettes. A few primary mossy fiber terminals labelled after cochlear injections are attributed to afferents from the lagenar macula. Since effective diffusion of label from the injection site was excluded by controls, it is concluded that projection of individual canal and macula nerves to the vestibulocerebellar cortex is not topographically separated. It is proposed that this extensive convergence of various afferents is required by the cerebellum to compute precise and directionally specific control signals during head rotation in all conceivable planes.« less

Analysis of the chicken retina with an adaptive optics multiphoton microscope

PubMed Central

Bueno, Juan M.; Giakoumaki, Anastasia; Gualda, Emilio J.; Schaeffel, Frank; Artal, Pablo

2011-01-01

The structure and organization of the chicken retina has been investigated with an adaptive optics multiphoton imaging microscope in a backward configuration. Non-stained flat-mounted retinal tissues were imaged at different depths, from the retinal nerve fiber layer to the outer segment, by detecting the intrinsic nonlinear fluorescent signal. From the stacks of images corresponding to the different retinal layers, volume renderings of the entire retina were reconstructed. The density of photoreceptors and ganglion cells layer were directly estimated from the images as a function of the retinal eccentricity. The maximum anatomical resolving power at different retinal eccentricities was also calculated. This technique could be used for a better characterization of retinal alterations during myopia development, and may be useful for visualization of retinal pathologies and intoxication during pharmacological studies. PMID:21698025

VOLTAGE CLAMP BEHAVIOR OF IRON-NITRIC ACID SYSTEM AS COMPARED WITH THAT OF NERVE MEMBRANE

PubMed Central

Tasaki, I.; Bak, A. F.

1959-01-01

The current-voltage relation for the surface layer of an iron wire immersed in nitric acid was investigated by the voltage clamp technique. Comparing the phase of nitric acid to the axoplasm and the metallic phase to the external fluid medium for the nerve fiber, a striking analogy was found between the voltage clamp behavior of the iron-nitric acid system and that of the nerve membrane. The current voltage curve was found to consist of three parts: (a) a straight line representing the behavior of the resting (passive) membrane, (b) a straight line representing the fully excited (active) state, and (c) an intermediate zone connecting (a) and (b). It was shown that in the intermediate zone, the surface of iron consisted of a fully active patch (or patches) surrounded by a remaining resting area. The phenomenon corresponding to "repetitive firing of responses under voltage clamp" in the nerve membrane was demonstrated in the intermediate zone. The behavior of the cobalt electrode system was also investigated by the same technique. An attempt was made to interpret the phenomenon of initiation and abolition of an active potential on the basis of the thermodynamics of irreversible processes. PMID:13654740

Engineering a multimodal nerve conduit for repair of injured peripheral nerve

NASA Astrophysics Data System (ADS)

Quigley, A. F.; Bulluss, K. J.; Kyratzis, I. L. B.; Gilmore, K.; Mysore, T.; Schirmer, K. S. U.; Kennedy, E. L.; O'Shea, M.; Truong, Y. B.; Edwards, S. L.; Peeters, G.; Herwig, P.; Razal, J. M.; Campbell, T. E.; Lowes, K. N.; Higgins, M. J.; Moulton, S. E.; Murphy, M. A.; Cook, M. J.; Clark, G. M.; Wallace, G. G.; Kapsa, R. M. I.

2013-02-01

Injury to nerve tissue in the peripheral nervous system (PNS) results in long-term impairment of limb function, dysaesthesia and pain, often with associated psychological effects. Whilst minor injuries can be left to regenerate without intervention and short gaps up to 2 cm can be sutured, larger or more severe injuries commonly require autogenous nerve grafts harvested from elsewhere in the body (usually sensory nerves). Functional recovery is often suboptimal and associated with loss of sensation from the tissue innervated by the harvested nerve. The challenges that persist with nerve repair have resulted in development of nerve guides or conduits from non-neural biological tissues and various polymers to improve the prognosis for the repair of damaged nerves in the PNS. This study describes the design and fabrication of a multimodal controlled pore size nerve regeneration conduit using polylactic acid (PLA) and (PLA):poly(lactic-co-glycolic) acid (PLGA) fibers within a neurotrophin-enriched alginate hydrogel. The nerve repair conduit design consists of two types of PLGA fibers selected specifically for promotion of axonal outgrowth and Schwann cell growth (75:25 for axons; 85:15 for Schwann cells). These aligned fibers are contained within the lumen of a knitted PLA sheath coated with electrospun PLA nanofibers to control pore size. The PLGA guidance fibers within the nerve repair conduit lumen are supported within an alginate hydrogel impregnated with neurotrophic factors (NT-3 or BDNF with LIF, SMDF and MGF-1) to provide neuroprotection, stimulation of axonal growth and Schwann cell migration. The conduit was used to promote repair of transected sciatic nerve in rats over a period of 4 weeks. Over this period, it was observed that over-grooming and self-mutilation (autotomy) of the limb implanted with the conduit was significantly reduced in rats implanted with the full-configuration conduit compared to rats implanted with conduits containing only an alginate hydrogel. This indicates return of some feeling to the limb via the fully-configured conduit. Immunohistochemical analysis of the implanted conduits removed from the rats after the four-week implantation period confirmed the presence of myelinated axons within the conduit and distal to the site of implantation, further supporting that the conduit promoted nerve repair over this period of time. This study describes the design considerations and fabrication of a novel multicomponent, multimodal bio-engineered synthetic conduit for peripheral nerve repair.

Cholera toxin B subunit labeling in lamina II of spinal cord dorsal horn following chronic inflammation in rats.

PubMed

Ma, Qing Ping; Tian, Li

2002-07-26

We have investigated the effect of inflammation on the labeling pattern of cholera toxin B subunit (CTB)-conjugated horseradish peroxidase, an A-fiber marker, by an intra-sciatic nerve injection of the tracer. Following chronic inflammation in one hind paw in rats, there was substantial CTB labeling in lamina II of the spinal dorsal horn, which is normally absent. However, there was no change in the labeling pattern of wheat germ agglutinin or fluoride resistant acid phosphatase/thiamine monophosphatase, two C-fiber markers. The CTB labeling in lamina II after peripheral nerve injury has been interpreted as central sprouting of A-fibers or uptake of the tracer by injured C-fibers. Our results suggest that chronic inflammation and nerve injury may share some common mechanisms in generating allodynia and hyperalgesia.

Sciatic endometriosis induces mechanical hypersensitivity, segmental nerve damage, and robust local inflammation in rats

PubMed Central

Chen, S.; Xie, W.; Strong, J. A.; Jiang, J.; Zhang, J.-M.

2015-01-01

Background Endometriosis is a common cause of pain including radicular pain. Ectopic endometrial tissue may directly affect peripheral nerves including the sciatic, which has not been modelled in animals. Methods We developed a rat model for sciatic endometriosis by grafting a piece of autologous uterine tissue around the sciatic nerve. Control animals underwent a similar surgery but received a graft of pelvic fat tissue. Results The uterine grafts survived and developed fluid filled cysts; the adjacent nerve showed signs of swelling and damage. Mechanical and cold hypersensitivity and allodynia of the ipsilateral hindpaw developed gradually over the first two weeks after the surgery, peaked at 2 to 5 weeks, and was almost resolved by 7 weeks. Control animals showed only minor changes in these pain behaviors. Histological signs of inflammation in the uterine graft and in the adjacent nerve were observed at 3 weeks but were resolving by 7 weeks. In vivo fiber recording showed increased spontaneous activity, especially of C fibers, in sciatic nerve proximal to the uterine graft. Several pro-inflammatory cytokines including interluekin-18, VEGF, fractalkine, and MIP-1α, were elevated in the uterine graft plus sciatic nerve samples, compared to samples from normal nerve or nerve plus fat graft. Growth associated protein 43 (GAP43), a marker of regenerating nerve fibers, was observed in the adjacent sciatic nerve as well as in the uterine graft. Conclusions This model shared many features with other rat models of endometriosis, but also had some unique features more closely related to neuropathic pain models. PMID:26688332

Emerging ocular biomarkers of Alzheimer disease.

PubMed

van Wijngaarden, Peter; Hadoux, Xavier; Alwan, Mostafa; Keel, Stuart; Dirani, Mohamed

2017-01-01

Interest in reliable biomarkers of Alzheimer disease, the leading cause of dementia, has been fuelled by challenges in diagnosing the disease and monitoring disease progression as well as the response to therapy. A range of ocular manifestations of Alzheimer disease, including retinal and lens amyloid-beta accumulation, retinal nerve fiber layer loss, and retinal vascular changes, have been proposed as potential biomarkers of the disease. Herein, we examine the evidence regarding the potential value of these ocular biomarkers of Alzheimer disease. © 2016 Royal Australian and New Zealand College of Ophthalmologists.

THE FINE STRUCTURE OF MEISSNER's TOUCH CORPUSCLES OF HUMAN FINGERS

PubMed Central

Cauna, Nikolajs; Ross, Leonard L.

1960-01-01

Thin slices of the finger pads of six individuals were fixed in buffered 1 per cent osmic acid, embedded in deaerated, nitrogenated methacrylate, and cut into thin sections for electron microscopic study. Before embedding, the slices were trimmed so as to include several digital tactile corpuscles. Some thin sections were stained in 10 per cent aqueous phosphotungstic acid solution. The principal part of Meissner's corpuscle is made up of flattened laminar cells stretching across the corpuscle in irregular layers. The perinuclear cytoplasm of these cells contains numerous small mitochondria, a sparse granular endoplasmic reticulum, and a large number of small vesicles. Nerve fibers enter the side or base of the corpuscle, lose their myelin sheaths, and follow a meandering course between the laminar cell plates. The nerve endings enter into a close appositional relationship with the flattened portions of the laminar cells. In some areas the apposed axolemma and cell membranes are slightly thickened with small vesicles located along the cell membrane or on both surfaces. These regions are interpreted as synapses. The most prominent feature of the nerve endings is an extraordinary accumulation of small mitochondria which vary in size and internal density. The nerve endings also contain vacuoles, groups of dense concentric membranes, and small dense vesicles of irregular distribution. The laminar cells are separated from one another by a dense intercellular substance of uniform thickness which also envelops the entire corpuscle. This material contains randomly oriented collagen fibers and fine fibrils bound together by a dense material at nodal points recurring at regular intervals of approximately 120 mµ. These findings are discussed in relation to the problems of the function of Meissner's corpuscle, neural material loss and replacement, and the presence of synapses. PMID:13691669

[Changes in facial nerve function, morphology and neurotrophic factor III expression following three types of facial nerve injury].

PubMed

Zhang, Lili; Wang, Haibo; Fan, Zhaomin; Han, Yuechen; Xu, Lei; Zhang, Haiyan

2011-01-01

To study the changes in facial nerve function, morphology and neurotrophic factor III (NT-3) expression following three types of facial nerve injury. Changes in facial nerve function (in terms of blink reflex (BF), vibrissae movement (VM) and position of nasal tip) were assessed in 45 rats in response to three types of facial nerve injury: partial section of the extratemporal segment (group one), partial section of the facial canal segment (group two) and complete transection of the facial canal segment lesion (group three). All facial nerves specimen were then cut into two parts at the site of the lesion after being taken from the lesion site on 1st, 7th, 21st post-surgery-days (PSD). Changes of morphology and NT-3 expression were evaluated using the improved trichrome stain and immunohistochemistry techniques ,respectively. Changes in facial nerve function: In group 1, all animals had no blink reflex (BF) and weak vibrissae movement (VM) at the 1st PSD; The blink reflex in 80% of the rats recovered partly and the vibrissae movement in 40% of the rats returned to normal at the 7th PSD; The facial nerve function in 600 of the rats was almost normal at the 21st PSD. In group 2, all left facial nerve paralyzed at the 1st PSD; The blink reflex partly recovered in 40% of the rats and the vibrissae movement was weak in 80% of the rats at the 7th PSD; 8000 of the rats'BF were almost normal and 40% of the rats' VM completely recovered at the 21st PSD. In group 3, The recovery couldn't happen at anytime. Changes in morphology: In group 1, the size of nerve fiber differed in facial canal segment and some of myelin sheath and axons degenerated at the 7th PSD; The fibres' degeneration turned into regeneration at the 21st PSD; In group 2, the morphologic changes in this group were familiar with the group 1 while the degenerated fibers were more and dispersed in transection at the 7th PSD; Regeneration of nerve fibers happened at the 21st PSD. In group 3, most of the fibers crumbled at the 7th PSD and no regeneration was seen at the 21st PSD. Changes in NT-3: Positive staining of NT-3 was largely observed in axons at the 7th PSD, although little NT-3 was seen in the normal fibers. Facial palsy of the rats in group 2 was more extensive than that in group 1 and their function partly recovers at the 21st PSD. The fibres' degeneration occurs not only dispersed throughout the injury site but also occurred throught the length of the nerve. NT-3 immunoreactivity increased in activated fibers after partial transection.

Taste bud-derived BDNF maintains innervation of a subset of TrkB-expressing gustatory nerve fibers.

PubMed

Tang, Tao; Rios-Pilier, Jennifer; Krimm, Robin

2017-07-01

Taste receptor cells transduce different types of taste stimuli and transmit this information to gustatory neurons that carry it to the brain. Taste receptor cells turn over continuously in adulthood, requiring constant new innervation from nerve fibers. Therefore, the maintenance of innervation to taste buds is an active process mediated by many factors, including brain-derived neurotrophic factor (BDNF). Specifically, 40% of taste bud innervation is lost when Bdnf is removed during adulthood. Here we speculated that not all gustatory nerve fibers express the BDNF receptor, TrkB, resulting in subsets of neurons that vary in their response to BDNF. However, it is also possible that the partial loss of innervation occurred because the Bdnf gene was not effectively removed. To test these possibilities, we first determined that not all gustatory nerve fibers express the TrkB receptor in adult mice. We then verified the efficiency of Bdnf removal specifically in taste buds of K14-CreER:Bdnf mice and found that Bdnf expression was reduced to 1%, indicating efficient Bdnf gene recombination. BDNF removal resulted in a 55% loss of TrkB-expressing nerve fibers, which was greater than the loss of P2X3-positive fibers (39%), likely because taste buds were innervated by P2X3+/TrkB- fibers that were unaffected by BDNF removal. We conclude that gustatory innervation consists of both TrkB-positive and TrkB-negative taste fibers and that BDNF is specifically important for maintaining TrkB-positive innervation to taste buds. In addition, although taste bud size was not affected by inducible Bdnf removal, the expression of the γ subunit of the ENaC channel was reduced. So, BDNF may regulate expression of some molecular components of taste transduction pathways. Copyright © 2017. Published by Elsevier Inc.

Cupping reversal in pediatric glaucoma--evaluation of the retinal nerve fiber layer and visual field.

PubMed

Ely, Amanda L; El-Dairi, Mays A; Freedman, Sharon F

2014-11-01

To identify optic nerve head (ONH) cupping reversal and associated optical coherence tomography (OCT) and Humphrey visual field changes in pediatric glaucoma. Retrospective observational case series. Sequential surgical cases of juvenile open-angle glaucoma (OAG) or primary congenital glaucoma (PCG) with sustained postoperative intraocular pressure (IOP) reduction. Group 1 had preoperative and postoperative ONH photographs and OCT; Group 2 had preoperative clinical ONH assessment and postoperative imaging. Cupping evaluation was confirmed by masked glaucoma and neuro-ophthalmology specialists. Of 80 cases, 9 eyes (9 children) met criteria for Group 1; 24 eyes (19 children) met criteria for Group 2. Group 1: Five of 9 eyes (56%) demonstrated cupping reversal, with preoperative vs postoperative mean IOP 34.2 ± 6.6 mm Hg vs 10.6 ± 4.1 mm Hg (P < .00001) and mean average retinal nerve fiber layer (RNFL) 71.0 ± 30 μm vs 62.8 ± 24 μm (P = .4), respectively. RNFL was stable in 4 of 5 eyes (all juvenile OAG), but thinned (Δ = -41 μm) in 1 eye with PCG. Humphrey visual fields (reliable in 2 of 3 eyes) showed no significant change. Group 2: Fourteen of 24 PCG eyes (58%) demonstrated cupping reversal, with preoperative vs postoperative mean IOP 36.1 ± 8.9 mm Hg vs 13.3 ± 2.1 mm Hg (P < .00001). Two eyes had thin RNFL postoperatively despite healthy-appearing ONH. Postoperative RNFL showed statistically significant linear correlation with preoperative (but not postoperative) cup-to-disc ratio. Limitations include small numbers, few reliable Humphrey visual fields, and absent preoperative imaging (Group 2). Some eyes with IOP reduction and ONH cupping reversal show continued RNFL thinning postoperatively. The preoperative ONH cup-to-disc ratio predicted the postoperative RNFL better than the postoperative "reversed and smaller" cup-to-disc ratio. Cupping reversal in pediatric glaucoma may not predict improved ONH health and deserves further study. Copyright © 2014 Elsevier Inc. All rights reserved.

Lamina cribrosa position and Bruch's membrane opening differences between anterior ischemic optic neuropathy and open-angle glaucoma.

PubMed

Rebolleda, Gema; Pérez-Sarriegui, Ane; Díez-Álvarez, Laura; De Juan, Victoria; Muñoz-Negrete, Francisco J

2018-06-01

To compare the optic nerve head morphology among primary open-angle glaucoma, non-arteritic anterior ischemic optic neuropathy eyes, their fellow healthy eyes and control eyes, using spectral-domain optical coherence tomography with enhanced depth imaging. Observational cross-sectional study including 88 eyes of 68 patients. In this study, 23 non-arteritic anterior ischemic optic neuropathy eyes, 17 fellow unaffected eyes, 25 primary open-angle glaucoma eyes, and 23 age-matched control eyes were included. Peripapillary retinal nerve fiber layer thickness and optic disk area were evaluated. Bruch's membrane opening diameter, optic cup depth, anterior lamina cribrosa depth, and prelaminar tissue thickness were assessed. Non-arteritic anterior ischemic optic neuropathy and primary open-angle glaucoma eyes had similar visual field mean deviation and peripapillary retinal nerve fiber layer thickness (P = 0.6 and P = 0.56, respectively). Bruch's membrane opening diameter was significantly larger in primary open-angle glaucoma eyes than in control eyes (P = 0.02). Lamina cribrosa and disk cup were deeper in eyes with primary open-angle glaucoma than both control and non-arteritic anterior ischemic optic neuropathy eyes (P < 0.001). Prelaminar tissue thickness was significantly thinner in primary open-angle glaucoma eyes than in non-arteritic anterior ischemic optic neuropathy eyes (P < 0.001). Lamina cribrosa was shallower in both non-arteritic anterior ischemic optic neuropathy and unaffected fellow eyes compared to healthy eyes (P < 0.001 and P = 0.04, respectively). No differences were found in the optic disk area. A forward lamina cribrosa placement and not a smaller disk could be involved in the pathogenesis of non-arteritic anterior ischemic optic neuropathy. A significantly larger Bruch's membrane opening diameter was found in primary open-angle glaucoma eyes compared with control eyes. This issue has clinical implications because Bruch's membrane opening has been considered a stable reference for disk-related measures.

Altered vesicular glutamate transporter distributions in the mouse cochlear nucleus following cochlear insult

PubMed Central

Heeringa, Amarins N.; Stefanescu, Roxana A.; Raphael, Yehoash; Shore, Susan E.

2015-01-01

Vesicular glutamate transporters 1 and 2 (VGLUT1 and VGLUT2) have distinct distributions in the cochlear nucleus that correspond to the sources of the labeled terminals. VGLUT1 is mainly associated with terminals of auditory nerve fibers, whereas VGLUT2 is mainly associated with glutamatergic terminals deriving from other sources that project to the cochlear nucleus (CN), including somatosensory and vestibular terminals. Previous studies in guinea pig have shown that cochlear damage results in a decrease of VGLUT1-labeled puncta and an increase in VGLUT2-labeled puncta. This indicates cross-modal compensation that is of potential importance in somatic tinnitus. To examine whether this effect is consistent across species and to provide a background for future studies, using transgenesis, the current study examines VGLUT expression profiles upon cochlear insult by intracochlear kanamycin injections in the mouse. Intracochlear kanamycin injections abolished ipsilateral ABR responses in all animals and reduced ipsilateral spiral ganglion neuron densities in animals that were sacrificed after four weeks, but not in animals that were sacrificed after three weeks. In all unilaterally deafened animals, VGLUT1 density was decreased in CN regions that receive auditory nerve fiber terminals, i.e. in the deep layer of the dorsal cochlear nucleus (DCN), in the interstitial region where the auditory nerve enters the CN, and in the magnocellular region of the antero- and posteroventral CN. In contrast, density of VGLUT2 expression was upregulated in the fusiform cell layer of the DCN and in the granule cell lamina, which are known to receive somatosensory and vestibular terminals. These results show that a cochlear insult induces cross-modal compensation in the cochlear nucleus of the mouse, confirming previous findings in guinea pig, and that these changes are not dependent on the occurrence of spiral ganglion neuron degeneration. PMID:26705736

Altered vesicular glutamate transporter distributions in the mouse cochlear nucleus following cochlear insult.

PubMed

Heeringa, A N; Stefanescu, R A; Raphael, Y; Shore, S E

2016-02-19

Vesicular glutamate transporters 1 and 2 (VGLUT1 and VGLUT2) have distinct distributions in the cochlear nucleus that correspond to sources of the labeled terminals. VGLUT1 is mainly associated with terminals of auditory nerve fibers, whereas VGLUT2 is mainly associated with glutamatergic terminals deriving from other sources that project to the cochlear nucleus (CN), including somatosensory and vestibular terminals. Previous studies in guinea pig have shown that cochlear damage results in a decrease of VGLUT1-labeled puncta and an increase in VGLUT2-labeled puncta. This indicates cross-modal compensation that is of potential importance in somatic tinnitus. To examine whether this effect is consistent across species and to provide a background for future studies, using transgenesis, the current study examines VGLUT expression profiles upon cochlear insult by intracochlear kanamycin injections in the mouse. Intracochlear kanamycin injections abolished ipsilateral ABR responses in all animals and reduced ipsilateral spiral ganglion neuron densities in animals that were sacrificed after four weeks, but not in animals that were sacrificed after three weeks. In all unilaterally deafened animals, VGLUT1 density was decreased in CN regions that receive auditory nerve fiber terminals, i.e., in the deep layer of the dorsal cochlear nucleus (DCN), in the interstitial region where the auditory nerve enters the CN, and in the magnocellular region of the antero- and posteroventral CN. In contrast, density of VGLUT2 expression was upregulated in the fusiform cell layer of the DCN and in the granule cell lamina, which are known to receive somatosensory and vestibular terminals. These results show that a cochlear insult induces cross-modal compensation in the cochlear nucleus of the mouse, confirming previous findings in guinea pig, and that these changes are not dependent on the occurrence of spiral ganglion neuron degeneration. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

A Digital Staining Algorithm for Optical Coherence Tomography Images of the Optic Nerve Head

PubMed Central

Mari, Jean-Martial; Aung, Tin; Cheng, Ching-Yu; Strouthidis, Nicholas G.; Girard, Michaël J. A.

2017-01-01

Purpose To digitally stain spectral-domain optical coherence tomography (OCT) images of the optic nerve head (ONH), and highlight either connective or neural tissues. Methods OCT volumes of the ONH were acquired from one eye of 10 healthy subjects. We processed all volumes with adaptive compensation to remove shadows and enhance deep tissue visibility. For each ONH, we identified the four most dissimilar pixel-intensity histograms, each of which was assumed to represent a tissue group. These four histograms formed a vector basis on which we ‘projected' each OCT volume in order to generate four digitally stained volumes P1 to P4. Digital staining was also verified using a digital phantom, and compared with k-means clustering for three and four clusters. Results Digital staining was able to isolate three regions of interest from the proposed phantom. For the ONH, the digitally stained images P1 highlighted mostly connective tissues, as demonstrated through an excellent contrast increase across the anterior lamina cribrosa boundary (3.6 ± 0.6 times). P2 highlighted the nerve fiber layer and the prelamina, P3 the remaining layers of the retina, and P4 the image background. Further, digital staining was able to separate ONH tissue layers that were not well separated by k-means clustering. Conclusion We have described an algorithm that can digitally stain connective and neural tissues in OCT images of the ONH. Translational Relevance Because connective and neural tissues are considerably altered in glaucoma, digital staining of the ONH tissues may be of interest in the clinical management of this pathology. PMID:28174676

The nervus terminalis in the chick: a FMRFamide-immunoreactive and AChE-positive nerve.

PubMed

Wirsig-Wiechmann, C R

1990-07-16

The chick terminal nerve (TN) was examined by immunocytochemical and histochemical methods. Molluscan cardioexcitatory peptide-immunoreactive (FMRFamide-ir) and acetylcholinesterase (AChE)-positive TN perikarya and fibers were distributed along olfactory and trigeminal nerves. FMRFamide-ir TN fibers terminated in the olfactory lamina propria and epithelium and in ganglia along the rostroventral nasal septum. This initial description of several populations of avian TN neurons should provide the foundation for future developmental studies of this system.

[Structural endpoints for glaucoma studies].

PubMed

Popa-Cherechenau, A; Schmidl, D; Garhöfer, G; Schmetterer, L

2018-03-06

Structural endpoints have been discussed as surrogate endpoints for the approval of neuroprotective drugs in glaucoma. Is the evidence strong enough to establish structural endpoints as surrogate endpoints? Review of current understanding between structure and function in glaucoma. The introduction of optical coherence tomography has revolutionized imaging in glaucoma patients. Clinically either the nerve fiber layer thickness can be measured along a circle centered in the optic nerve head or the ganglion cell layer thickness can be assessed in the macular region, the latter being quantified in combination with other inner retinal layers. On a microscopic level there is a strong correlation between structural and functional loss but this relation can only partially be described with currently available clinical methods. This is particularly true for longitudinal course of the disease in glaucoma patients. Novel imaging techniques that are not yet used clinically may have the potential to increase our understanding between structure and function in glaucoma but further research in this field is required. The current evidence does not allow the establishment of structural endpoints as surrogate endpoints for phase 3 studies in glaucoma. Neuroprotective drugs have to be approved on the basis of visual field data because this is the patient-relevant endpoint. Structural endpoints can, however, play an important role in phase 2 and proof of concept studies.

[Expression of vimentin and GFAP and development of the retina in the trout].

PubMed

De Guevara, R; Pairault, C; Pinganaud, G

1994-08-01

The glial cell development was studied during the edification of the retina and the optic tract, in a teleost, the rainbow trout. The intermediate filament proteins, vimentin and glial fibrillary acidic protein (GFAP) were visualized by an indirect immunohistochemical method. Results show that both vimentin and GFAP are early expressed in the developing retina and, particularly in the Müller cells, a coexpression of vimentin and GFAP is observed from embryonic to adult stages. The ganglion cell layer and the optic fiber layer both exhibit GFAP-positive structures. The deep staining for GFAP is also seen in the optic nerve and induces us to credit astrocyte-like cells with a leading role in the pattern formation of this tract.

Autonomic nerve development contributes to prostate cancer progression.

PubMed

Magnon, Claire; Hall, Simon J; Lin, Juan; Xue, Xiaonan; Gerber, Leah; Freedland, Stephen J; Frenette, Paul S

2013-07-12

Nerves are a common feature of the microenvironment, but their role in tumor growth and progression remains unclear. We found that the formation of autonomic nerve fibers in the prostate gland regulates prostate cancer development and dissemination in mouse models. The early phases of tumor development were prevented by chemical or surgical sympathectomy and by genetic deletion of stromal β2- and β3-adrenergic receptors. Tumors were also infiltrated by parasympathetic cholinergic fibers that promoted cancer dissemination. Cholinergic-induced tumor invasion and metastasis were inhibited by pharmacological blockade or genetic disruption of the stromal type 1 muscarinic receptor, leading to improved survival of the mice. A retrospective blinded analysis of prostate adenocarcinoma specimens from 43 patients revealed that the densities of sympathetic and parasympathetic nerve fibers in tumor and surrounding normal tissue, respectively, were associated with poor clinical outcomes. These findings may lead to novel therapeutic approaches for prostate cancer.

The gross anatomy of the renal sympathetic nerves revisited.

PubMed

Mompeo, Blanca; Maranillo, Eva; Garcia-Touchard, Arturo; Larkin, Theresa; Sanudo, Jose

2016-07-01

Catheter-based renal denervation techniques focus on reducing blood pressure in resistant hypertension. This procedure requires exact knowledge of the anatomical interrelation between the renal arteries and the targeted renal nervous plexus. The aim of this work was to build on classical anatomical studies and describe the gross anatomy and anatomical relationships of the renal arteries and nerve supply to the kidneys in a sample of human cadavers. Twelve human cadavers (six males and six females), age range 73 to 94 years, were dissected. The nervous fibers and renal arteries were dissected using a surgical microscope. The renal plexus along the hilar renal artery comprised a fiber-ganglionic ring surrounding the proximal third of the renal artery, a neural network along the middle and distal thirds, and smaller accessory ganglia along the course of the nerve fibers. The fibers of the neural network were mainly located on the superior (95.83%) and inferior (91.66%) surfaces of the renal artery and they were sparsely interconnected by diagonal fibers. Polar arteries were present in 33.33% of cases and the renal nerve pattern for these was similar to that of the hilar arteries. Effective renal denervation needs to target the superior and inferior surfaces of the hilar and polar arteries, where the fibers of the neural network are present. Clin. Anat. 29:660-664, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Receptive fields and gustatory responsiveness of frog glossopharyngeal nerve. A single fiber analysis

PubMed Central

1990-01-01

Receptive fields and responsiveness of single fibers of the glossopharyngeal (IXth) nerve were investigated using electrical, gustatory (NaCl, quinine HCl, acetic acid, water, sucrose, and CaCl2), thermal, and mechanical stimulation of the single fungiform papillae distributed on the dorsal tongue surface in frogs. 172 single fibers were isolated. 58% of these fibers (99/172) were responsive to at least one of the gustatory stimuli (taste fibers), and the remaining 42% (73/172) were responsive only to touch (touch fibers). The number of papillae innervated by a single fiber (receptive field) was between 1 and 17 for taste fibers and between 1 and 10 for touch fibers. The mean receptive field of taste fibers (X = 6.6, n = 99) was significantly larger than that of touch fibers (X = 3.6, n = 73) (two-tailed t test, P less than 0.001). In experiments with natural stimulation of single fungiform papillae, it was found that every branch of a single fiber has a similar responsiveness. Taste fibers were classified into 14 types (Type N, Q, A, NA, NCa, NCaA, NCaW, NCaAW, NCaWS, NQ, NQA, NQAS, NQWarm, Multiple) on the basis of their responses to gustatory and thermal stimuli. The time course of the response in taste fibers was found to be characteristic of their types. For example, the fibers belonging to Type NQA showed phasic responses, those in Type NCa showed tonic responses, etc. These results indicate that there are several groups of fibers in the frog IXth nerve and that every branch of an individual fiber has a similar responsiveness to the parent fiber. PMID:2374001

[Revealing the structure of the nervous tissue III: From Jan Evangelista Purkyne (1787-1869) to Ludwig Mauthner (1840-1894)].

PubMed

Chvátal, A

2015-01-01

The works of Jan Evangelista Purkyne, Gabriel Valentin and Robert Remak showed that the nervous system contains not only nerve fibers, but also cellular elements. The use of microscopes and new fixation techniques have enabled the retrieval of accurate data on the structure of nervous tissue and in many European universities microscopes began to be widely used for histological and morphological studies. The present review summarizes the discoveries of the structure of predominantly vertebrate nerve tissue during the period from 1838 to 1865, made by prominent scholars who described the structure of fibers and cells of the nervous system and demonstrated that some nerve fibers are enwrapped by a sheath. In addition, the first attempts were made to make a cytoarchitectonic description of the spinal cord and brain. During the same time the concept of a neuroglial tissue was introduced, first as a tissue for "gluing" nerve fibers, cells and blood capillaries into one unit, but later some glial cells were described for the first time. Microscopic techniques started to be used for examination of physiological as well as pathological nerve tissues. The overall state of knowledge was just a step away from the emergence of the concept of neurons and glial cells.

Microcircuits in the Nervous System

ERIC Educational Resources Information Center

Shepherd, Gordon M.

1978-01-01

Nerve circuits are usually analyzed in terms of the axon, the long fiber of the nerve cell. It now appears that there are many circuits involving only the nerve cell's shorter extensions, the dendrites. (Author/BB)

Electrophysiologic alterations in the excitability of the sciatic and vagus nerves during early stages of sepsis

PubMed Central

Diniz, Lúcio Ricardo Leite; Portella, Viviane Gomes; da Silva Alves, Kerly Shamira; Araújo, Pâmella Cristina da Costa; de Albuquerque Júnior, Ricardo Luiz Cavalcanti; Cavalcante de Albuquerque, Aline Alice; Coelho-de-Souza, Andrelina Noronha; Leal-Cardoso, José Henrique

2018-01-01

Background Nonspecific and delayed diagnosis of neurologic damage contributes to the development of neuropathies in patients with severe sepsis. The present study assessed the electrophysiologic parameters related to the excitability and conductibility of sciatic and vagus nerves during early stages of sepsis. Materials and methods Twenty-four hours after sepsis induced by cecal ligation and puncture (CLP) model, sciatic and vagus nerves of septic (CLP group) and control (sham group) rats were removed, and selected electric stimulations were applied to measure the parameters of the first and second components of the compound action potential. The first component originated from fibers with motor and sensory functions (Types Aα and Aβ fibers) with a large conduction velocity (70–120 m/s), and the second component originated from fibers (Type Aγ) with sensorial function. To evaluate the presence of sensorial alterations, the sensitivity to non-noxious mechanical stimuli was measured by using the von Frey test. Hematoxylin and eosin staining of the nerves was performed. Results We observed an increase of rheobase followed by a decrease in the first component amplitude and a higher paw withdrawal threshold in response to the application of von Frey filaments in sciatic nerves from the CLP group compared to the sham group. Differently, a decrease in rheobase and an increase in the first component amplitude of vagal C fibers from CLP group were registered. No significant morphologic alteration was observed. Conclusion Our data showed that the electrophysiologic alterations in peripheral nerves vary with the fiber type and might be identified in the first 24 h of sepsis, before clinical signs of neuromuscular disorders. PMID:29731661

Influence of limb temperature on cutaneous silent periods.

PubMed

Kofler, Markus; Valls-Solé, Josep; Vasko, Peter; Boček, Václav; Štetkárová, Ivana

2014-09-01

The cutaneous silent period (CSP) is a spinal inhibitory reflex mediated by small-diameter afferents (A-delta fibers) and large-diameter efferents (alpha motoneurons). The effect of limb temperature on CSPs has so far not been assessed. In 27 healthy volunteers (11 males; age 22-58 years) we recorded median nerve motor and sensory action potentials, median nerve F-wave and CSPs induced by noxious digit II stimulation in thenar muscles in a baseline condition at room temperature, and after randomly submersing the forearm in 42 °C warm or 15 °C cold water for 20 min each. In cold limbs, distal and proximal motor and sensory latencies as well as F-wave latencies were prolonged. Motor and sensory nerve conduction velocities were reduced. Compound motor and sensory nerve action potential amplitudes did not differ significantly from baseline. CSP onset and end latencies were more delayed than distal and proximal median nerve motor and sensory latencies, whereas CSP duration was not affected. In warm limbs, opposite but smaller changes were seen in nerve conduction studies and CSPs. The observed CSP shift "en bloc" towards longer latencies without affecting CSP duration during limb cooling concurs with slower conduction velocity in both afferent and efferent fibers. Disparate conduction slowing in afferents and efferents, however, suggests that nociceptive EMG suppression is mediated by fibers of different size in the afferent than in the efferent arm, indirectly supporting the contribution of A-delta fibers as the main afferent input. Limb temperature should be taken into account when testing CSPs in the clinical setting, as different limb temperatures affect CSP latencies more than large-diameter fiber conduction function. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Motor nerve transplantation.

PubMed

Gray, W P; Keohane, C; Kirwan, W O

1997-10-01

The motor nerve transplantation (MNT) technique is used to transfer an intact nerve into a denervated muscle by harvesting a neurovascular pedicle of muscle containing motor endplates from the motor endplate zone of a donor muscle and implanting it into a denervated muscle. Thirty-six adult New Zealand White rabbits underwent reinnervation of the left long peroneal (LP) muscle (fast twitch) with a motor nerve graft from the soleus muscle (slow twitch). The right LP muscle served as a control. Reinnervation was assessed using microstimulatory single-fiber electromyography (SFEMG), alterations in muscle fiber typing and grouping, and isometric response curves. Neurofilament antibody was used for axon staining. The neurofilament studies provided direct evidence of nerve growth from the motor nerve graft into the adjacent denervated muscle. Median motor endplate jitter was 13 microsec preoperatively, and 26 microsec at 2 months, 29.5 microsec at 4 months, and 14 microsec at 6 months postoperatively (p < 0.001). Isometric tetanic tension studies showed a progressive functional recovery in the reinnervated muscle over 6 months. There was no histological evidence of aberrant reinnervation from any source outside the nerve pedicle. Isometric twitch responses and adenosine triphosphatase studies confirmed the conversion of the reinnervated LP muscle to a slow-type muscle. Acetylcholinesterase studies confirmed the presence of functioning motor endplates beneath the insertion of the motor nerve graft. It is concluded that the MNT technique achieves motor reinnervation by growth of new nerve fibers across the pedicle graft into the recipient muscle.

Effects of hyperglycemia on rat cavernous nerve axons: a functional and ultrastructural study.

PubMed

Zotova, Elena G; Schaumburg, Herbert H; Raine, Cedric S; Cannella, Barbara; Tar, Moses; Melman, Arnold; Arezzo, Joseph C

2008-10-01

The present study explored parallel changes in the physiology and structure of myelinated (Adelta) and unmyelinated (C) small diameter axons in the cavernous nerve of rats associated with streptozotocin-induced hyperglycemia. Damage to these axons is thought to play a key role in diabetic autonomic neuropathy and erectile dysfunction, but their pathophysiology has been poorly studied. Velocities in slow conducting fibers were measured by applying multiple unit procedures; histopathology was evaluated with both light and electron microscopy. To our knowledge, these are the initial studies of slow nerve conduction velocities in the distal segments of the cavernous nerve. We report that hyperglycemia is associated with a substantial reduction in the amplitude of the slow conducting response, as well as a slowing of velocities within this very slow range (< 2.5 m/s). Even with prolonged hyperglycemia (> 4 months), histopathological abnormalities were mild and limited to the distal segments of the cavernous nerve. Structural findings included dystrophic changes in nerve terminals, abnormal accumulations of glycogen granules in unmyelinated and preterminal axons, and necrosis of scattered smooth muscle fibers. The onset of slowing of velocity in the distal cavernous nerve occurred subsequent to slowing in somatic nerves in the same rats. The functional changes in the cavernous nerve anticipated and exceeded the axonal degeneration detected by morphology. The physiologic techniques outlined in these studies are feasible in most electrophysiologic laboratories and could substantially enhance our sensitivity to the onset and progression of small fiber diabetic neuropathy.

EFFECTS OF HYPERGLYCEMIA ON RAT CAVERNOUS NERVE AXONS: A FUNCTIONAL AND ULTRASTRUCTURAL STUDY

PubMed Central

Zotova, Elena G.; Schaumburg, Herbert H.; Raine, Cedric S.; Cannella, Barbara; Tar, Moses; Melman, Arnold; Arezzo, Joseph C.

2008-01-01

The present study explored parallel changes in the physiology and structure of myelinated (Aδ) and unmyelinated (C) small diameter axons in the cavernous nerve of rats associated with streptozotocin-induced hyperglycemia. Damage to these axons is thought to play a key role in diabetic autonomic neuropathy and erectile dysfunction, but their pathophysiology has been poorly studied. Velocities in slow conducting fibers were measured by applying multiple unit procedures; histopathology was evaluated with both light and electron microscopy. To our knowledge, these are the initial studies of slow nerve conduction velocities in the distal segments of the cavernous nerve. We report that hyperglycemia is associated with a substantial reduction in the amplitude of the slow conducting response, as well as a slowing of velocities within this very slow range (<2.5 m/sec). Even with prolonged hyperglycemia (> 4 months), histopathological abnormalities were mild and limited to the distal segments of the cavernous nerve. Structural findings included dystrophic changes in nerve terminals, abnormal accumulations of glycogen granules in unmyelinated and preterminal axons, and necrosis of scattered smooth muscle fibers. The onset of slowing of velocity in the distal cavernous nerve occurred subsequent to slowing in somatic nerves in the same rats. The functional changes in the cavernous nerve anticipated and exceeded the axonal degeneration detected by morphology. The physiologic techniques outlined in these studies are feasible in most electrophysiologic laboratories and could substantially enhance our sensitivity to the onset and progression of small fiber diabetic neuropathy. PMID:18687329

Diffusion Tensor Imaging Tractography Detecting Isolated Oculomotor Nerve Damage After Traumatic Brain Injury.

PubMed

Jacquesson, Timothée; Frindel, Carole; Cotton, Francois

2017-04-01

A 24-year-old woman was hit by a bus and suffered an isolated complete oculomotor nerve palsy. Computed tomography scan did not show a skull base fracture. T2*-weighted magnetic resonance imaging revealed petechial cerebral hemorrhages sparing the brainstem. T2 constructive interference in steady state suggested a partial sectioning of the left oculomotor nerve just before entering the superior orbital fissure. Diffusion tensor imaging fiber tractography confirmed a sharp arrest of the left oculomotor nerve. This recent imaging technique could be of interest to assess white fiber damage and help make a diagnosis or prognosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Surgical anatomy of the prostate in the era of radical robotic prostatectomy.

PubMed

Walz, Jochen; Graefen, Markus; Huland, Hartwig

2011-05-01

New insights in the anatomy of the prostate and the surrounding tissue evolve the technique of radical prostatectomy for the treatment of prostate cancer. Regarding the course of the erectile nerves along the prostate, recent studies confirmed the presence of parasympathetic pro-erectile nerve fibers at the anterolateral aspect of the prostate. Another study of intraoperative electrostimulation of those nerves confirmed an increase in intracavernosal pressure by stimulations between the 1 and 3 o'clock position. Therefore, it is very likely that these anterior nerve fibers have an effect on erectile function. Regarding the urethral sphincter in the male, a study showed no attachment of the external sphincter to the levator ani muscle, probably resulting in an absence of a levator ani support to the continence mechanism. The male urinary sphincter seems to be in isolation responsible for urinary continence. The nerve fibers at the anterolateral aspect of the prostate seem to participate in erectile function, which renders the concept of a high anterior release during nerve sparing beneficial. The isolated urinary sphincter mechanism results in the need to conserve as much urethral length as possible during radical prostatectomy to avoid urinary incontinence.

Neovascularization and neoinnervation of subcutaneously placed nucleus pulposus and the inhibitory effects of certain drugs.

PubMed

Olmarker, Kjell

2005-07-01

An experimental study in the pig with autologous transfer of nucleus pulpous and retroperitoneal fat to the subcutaneous space of the back. To evaluate if there is neovascularization or neoinnervation of subcutaneously placed nucleus pulposus, in comparison to retroperitoneal fat, and under simultaneous treatment by certain antiangiogenetic drugs. It has been suggested that intervertebral discs may be invaded by newly formed blood vessels and nerve fibers following injury of the anulus fibrosus. The nerve fibers have been considered to induce low back pain. However, it is still debated whether such ingrowth may occur and, if present, if this is based on the action of angiogenetic substances in the intervertebral disc or simply by normal would healing. In the first series, autologous nucleus pulposus and retroperitoneal fat was placed subcutaneously in 3 pigs. In the second series, autologous nucleus pulposus was placed subcutaneously with simultaneous treatment with methotrexate (n = 3), celecoxib (n = 3), doxycycline (n = 3), and infliximab (n = 3). After 7 days, the tissue was collected and processed immunohistochemically for the visualization of blood vessels and nerve fibers. There was a number of blood vessels and nerve fibers in the nucleus pulposus samples, while no vessels were observed in the fat samples. Neither methotrexate nor celecoxib seemed to be able to reduce the ingrowth of blood vessels (neovascularization) or nerve fibers (neoinnervation). Treatment by doxycycline and infliximab markedly reduced both neovascularization and neoinnervation. Subcutaneously placed autologous nucleus pulposus displays an ingrowth of newly formed blood vessels and nerve fibers within 7 days, in contrast to retroperitoneal fat. Such ingrowth seems to be reduced by doxycycline and infliximab, 2 cytokine inhibitors. The data suggest that the ingrowth may be induced by bioactive substances within the nucleus pulposus. The clinical importance of these data has yet to be elucidated.

Lack of effectiveness of laser therapy applied to the nerve course and the correspondent medullary roots

PubMed Central

Sousa, Fausto Fernandes de Almeida; Ribeiro, Thaís Lopes; Fazan, Valéria Paula Sassoli; Barbieri, Claudio Henrique

2013-01-01

OBJECTIVE: To investigate the influence of low intensity laser irradiation on the regeneration of the fibular nerve of rats after crush injury. METHODS: Twenty-five rats were used, divided into three groups: 1) intact nerve, no treatment; 2) crushed nerve, no treatment; 3) crush injury, laser irradiation applied on the medullary region corresponding to the roots of the sciatic nerve and subsequently on the course of the damaged nerve. Laser irradiation was carried out for 14 consecutive days. RESULTS: Animals were evaluated by functional gait analysis with the peroneal functional index and by histomorphometric analysis using the total number of myelinated nerve fibers and their density, total number of Schwann cells, total number of blood vessels and the occupied area, minimum diameter of the fiber diameter and G-quotient. CONCLUSION: According to the statistical analysis there was no significant difference among groups and the authors conclude that low intensity laser irradiation has little or no influence on nerve regeneration and functional recovery. Laboratory investigation. PMID:24453650

Automated classifiers for early detection and diagnosis of retinopathy in diabetic eyes.

PubMed

Somfai, Gábor Márk; Tátrai, Erika; Laurik, Lenke; Varga, Boglárka; Ölvedy, Veronika; Jiang, Hong; Wang, Jianhua; Smiddy, William E; Somogyi, Anikó; DeBuc, Delia Cabrera

2014-04-12

Artificial neural networks (ANNs) have been used to classify eye diseases, such as diabetic retinopathy (DR) and glaucoma. DR is the leading cause of blindness in working-age adults in the developed world. The implementation of DR diagnostic routines could be feasibly improved by the integration of structural and optical property test measurements of the retinal structure that provide important and complementary information for reaching a diagnosis. In this study, we evaluate the capability of several structural and optical features (thickness, total reflectance and fractal dimension) of various intraretinal layers extracted from optical coherence tomography images to train a Bayesian ANN to discriminate between healthy and diabetic eyes with and with no mild retinopathy. When exploring the probability as to whether the subject's eye was healthy (diagnostic condition, Test 1), we found that the structural and optical property features of the outer plexiform layer (OPL) and the complex formed by the ganglion cell and inner plexiform layers (GCL + IPL) provided the highest probability (positive predictive value (PPV) of 91% and 89%, respectively) for the proportion of patients with positive test results (healthy condition) who were correctly diagnosed (Test 1). The true negative, TP and PPV values remained stable despite the different sizes of training data sets (Test 2). The sensitivity, specificity and PPV were greater or close to 0.70 for the retinal nerve fiber layer's features, photoreceptor outer segments and retinal pigment epithelium when 23 diabetic eyes with mild retinopathy were mixed with 38 diabetic eyes with no retinopathy (Test 3). A Bayesian ANN trained on structural and optical features from optical coherence tomography data can successfully discriminate between healthy and diabetic eyes with and with no retinopathy. The fractal dimension of the OPL and the GCL + IPL complex predicted by the Bayesian radial basis function network provides better diagnostic utility to classify diabetic eyes with mild retinopathy. Moreover, the thickness and fractal dimension parameters of the retinal nerve fiber layer, photoreceptor outer segments and retinal pigment epithelium show promise for the diagnostic classification between diabetic eyes with and with no mild retinopathy.

High resolution retinal scanning reveals regional structural differences between MS and NMOSD optic neuritis regardless of antibody status.

PubMed

Bertsch-Gout, Marcel; Loeb, Richard; Finch, Ashley K; Javed, Adil; Bernard, Jacqueline

2018-01-15

There is a need for biomarkers that can classify optic neuritis (ON) attacks as belonging to either neuromyelitis optica spectrum disorder with optic neuritis (NMOSD-ON) or relapsing remitting multiple sclerosis with optic neuritis (MS-ON). This study uses spectral domain optical coherence tomography (SD-OCT) data to perform a preliminary contrast between NMOSD-ON and MS-ON by analyzing peripapillary retinal nerve fiber layer and intra-macular layer patterns of injury. In this cross-sectional study, we used SD-OCT to obtain peripapillary retinal nerve fiber layer and intra-macular layer data for 26 NMOSD-ON, 25 MS-ON, and 26 healthy control (HC) age-matched eyes. Additionally, sub-comparisons compared 11 NMOSD-ON eyes that were seronegative for IgG antibodies against aquaporin 4 (NMOSD-ON (-)) and 16 NMOSD-ON eyes that were seropositive (NMOSD-ON (+)) to age-matched MS-ON eyes. Layer thicknesses were assessed using an automated algorithm and were then statistically compared using generalized estimating equations to account for inter-eye correlations. Selective thinning was found in the pRNFL, mRNFL, and GCL in NMOSD-ON compared to MS-ON. Thinning in the pRNFL nasal sector was found to persist in both NMOSD-ON (-) (P=0.017) and NMOSD-ON (+) (P=0.021) compared to MS-ON. Thinning in the mRNFL temporal sector was found to persist in NMOSD-ON (+) compared to MS-ON. Diffuse thinning was found in the pRNFL, mRNFL, GCL and IPL in NMOSD-ON compared to HC, and while diffuse thinning was also found in the GCL and IPL in MS-ON compared to HC, selective thinning was found in the pRNFL and mRNFL. The nasal region of the pRNFL may be capable of distinguishing between NMOSD-ON and MS-ON regardless of antibody status. Additionally, NMOSD-ON may cause more profound nasal axonal and inferior arcuate neuronal degeneration compared to MS-ON. Copyright © 2017 Elsevier B.V. All rights reserved.

Incorporation of fiber optic beam shaping into a laparoscopic probe for laser stimulation of the cavernous nerves

NASA Astrophysics Data System (ADS)

Tozburun, Serhat; Lagoda, Gwen A.; Mayeh, Mona; Burnett, Arthur L.; Farahi, Faramarz; Fried, Nathaniel M.

2010-02-01

The cavernous nerves (CN) course along the prostate surface and are responsible for erectile function. Improved identification and preservation of the CN's is critical to maintaining sexual potency after prostate cancer surgery. Noncontact optical nerve stimulation (ONS) of the CN's was recently demonstrated in a rat model, in vivo, as a potential alternative to electrical nerve stimulation (ENS) for identification of the CN's during prostate surgery. However, the therapeutic window for ONS is narrow, so optimal design of the fiber optic delivery system is critical for safe, reproducible stimulation. This study describes modeling, assembly, and testing of an ONS probe for delivering a small, collimated, flat-top laser beam for uniform CN stimulation. A direct comparison of the magnitude and response time of the intracavernosal pressure (ICP) for both Gaussian and flat-top spatial beam profiles was performed. Thulium fiber laser radiation (λ=1870 nm) was delivered through a 200-μm fiber, with distal fiber tip chemically etched to convert a Gaussian to flat-top beam profile. The laser beam was collimated to a 1-mm-diameter spot using an aspheric lens. Computer simulations of light propagation were used to optimize the probe design. The 10-Fr (3.4-mm-OD) laparoscopic probe provided a constant radiant exposure at the nerve surface. The probe was tested in four rats, in vivo. ONS of the CN's was performed with a 1-mm-diameter spot, 5- ms pulse duration, and pulse rate of 20 Hz for a duration of 15-30 s. The flat-top laser beam profile consistently produced a faster and higher ICP response at a lower radiant exposure than the Gaussian beam profile due, in part, to easier alignment of the more uniform beam with nerve. With further development, ONS may be used as a diagnostic tool for identification of the CN's during laparoscopic and robotic nerve-sparing prostate cancer surgery.

Ontogeny and innervation of taste buds in mouse palatal gustatory epithelium.

PubMed

Rashwan, Ahmed; Konishi, Hiroyuki; El-Sharaby, Ashraf; Kiyama, Hiroshi

2016-01-01

We investigated the relationship between mouse taste bud development and innervation of the soft palate. We employed scanning electron microscopy and immunohistochemistry using antibodies against protein gene product 9.5 and peripherin to detect sensory nerves, and cytokeratin 8 and α-gustducin to stain palatal taste buds. At E14, nerve fibers were observed along the medial border of the palatal shelves that tracked toward the epithelium. At E15.5, primordial stages of taste buds in the basal lamina of the soft palate first appeared. At E16, the taste buds became large spherical masses of columnar cells scattered in the soft palate basal lamina. At E17, the morphology and also the location of taste buds changed. At E18-19, some taste buds acquired a more elongated shape with a short neck, extending a variable distance from the soft palate basal lamina toward the surface epithelium. At E18, mature taste buds with taste pores and perigemmal nerve fibers were observed on the surface epithelium of the soft palate. The expression of α-gustducin was demonstrated at postnatal day 1 and the number of pored taste buds increased with age and they became pear-shaped at 8 weeks. The percent of pored fungiform-like papillae at birth was 58.3% of the whole palate; this increased to 83.8% at postnatal day 8 and reached a maximum of 95.7% at 12 weeks. The innervation of the soft palate was classified into three types of plexuses in relation to taste buds: basal nerve plexus, intragemmal and perigemmal nerve fibers. This study reveals that the nerve fibers preceded the development of taste buds in the palate of mice, and therefore the nerve fibers have roles in the initial induction of taste buds in the soft palate. Copyright © 2015 Elsevier B.V. All rights reserved.

[Changes in the electrical activity of the rabbit proximal colon in vivo by stimulation of the vagus and splanchnic nerves].

PubMed

Julé, Y

1975-05-01

1. Using extracellular electrodes placed on the serosa, we recorded the modifications of the electrical activity of the colonic muslce fibers caused by the stimulation of vagal and splanchnic nerve fibers. 2. Vagal stimulation produces two types of junction potentials: excitatory junction potentials (EJPs) and inhibitory junction potentials (IJPs). The IJPs are elicited by stimulation of vagal fibers which innervate intramural non-adrenergic inhibitory neurons. 3. The conduction velocity of the nerve impulse along the vagal pre-ganglionic fibers is 1.01 m/sec for excitatory fibers and 0.5. m/sec for inhibitory fibers. 4. Splanchnic fiber stimulation causes EJP disappearance, blocking transmission between preganglionic fibers and intramural excitatory neurons, and a decrease in IJP amplitude that most likely indicates a previous hyperpolarization of the smooth muscle. 5. IJP persistence during splanchnic stimulation proves that sympathetic inhibition does not modify the transmission of the vagal influx onto the non-adrenergic inhibitory neurons of the intramural plexuses. 6. Through a comparative study of proximal and distal colonic innervation, we are able to show that there is a similar organization of both regions, that is a double inhibitory innervation: an adrenergic one of a sympathetic origin, and a non adrenergic one of a parasympathetic origin.

Upregulation of the axonal growth and the expression of substance P and its NK1 receptor in human allergic contact dermatitis.

PubMed

El-Nour, H; Lundeberg, L; Al-Tawil, R; Granlund, A; Lonne-Rahm, S-B; Nordlind, K

2006-01-01

Nerve fibers and sensory neuropeptides substance P and calcitonin gene-related peptide (CGRP) have been reported to be involved in allergic contact dermatitis (ACD). In the present study, we investigated the general innervation (using antibody against protein gene product 9.5, PGP 9.5), axonal growth (using antibody against growth associated protein, GAP-43), CGRP, and substance P with its receptor neurokinin 1 (NK1), in positive epicutaneous reactions to nickel sulphate from nickel-allergic patients, at the peak of inflammation, 72 hr after challenge with the antigen. There was an increased (p < 0.01) number of GAP-43 positive fibers in the eczematous compared with control skin, indicating an increased axonal growth already at 72 hr postchallenge. Double staining revealed a coexpression of CGRP and GAP-43 on dermal nerve fibers. There was no difference in the number of substance P and CGRP positive nerve fibers between eczematous and control skin. However, semiquantification analyses showed an increased expression of substance P positive inflammatory cells, being CD3, CD4, or CD8 positive, and NK1R positive inflammatory cells, being tryptase or CD3 positive. These results indicate a contribution of regenerating nerve fibers and substance P to the contact allergic reaction.

Nervus terminalis, olfactory nerve, and optic nerve representation of luteinizing hormone-releasing hormone in primates.

PubMed

Witkin, J W

1987-01-01

The luteinizing hormone-releasing hormone (LHRH) system was examined immunocytochemically in olfactory bulbs of adult monkeys, including two New World species (squirrel monkey, Saimiri sciureus and owl monkey, Aotus trivirgatus) and one Old World species (cynomolgus macaque, Macaca fasciculata), and in the brain and nasal region of a fetal rhesus macaque Macaca mulatta. LHRH neurons and fibers were found sparsely distributed in the olfactory bulbs in all adult monkeys. There was more LHRH in the accessory olfactory bulb (which is absent in Old World monkeys). In the fetal macaque there was a rich distribution of LHRH neurons and fibers along the pathway of the nervus terminalis, anterior and ventral to the olfactory bulb, and in the nasal septum, with fibers branching into the olfactory epithelium. In addition, there were LHRH neurons and fibers in the optic nerve.

Schwann cell glycogen selectively supports myelinated axon function.

PubMed

Brown, Angus M; Evans, Richard D; Black, Joel; Ransom, Bruce R

2012-09-01

Interruption of energy supply to peripheral axons is a cause of axon loss. We determined whether glycogen was present in mammalian peripheral nerve, and whether it supported axon conduction during aglycemia. We used biochemical assay and electron microscopy to determine the presence of glycogen, and electrophysiology to monitor axon function. Glycogen was present in sciatic nerve, its concentration varying directly with ambient glucose. Electron microscopy detected glycogen granules primarily in myelinating Schwann cell cytoplasm, and these diminished after exposure to aglycemia. During aglycemia, conduction failure in large myelinated axons (A fibers) mirrored the time course of glycogen loss. Latency to compound action potential (CAP) failure was directly related to nerve glycogen content at aglycemia onset. Glycogen did not benefit the function of slow-conducting, small-diameter unmyelinated axons (C fibers) during aglycemia. Blocking glycogen breakdown pharmacologically accelerated CAP failure during aglycemia in A fibers, but not in C fibers. Lactate was as effective as glucose in supporting sciatic nerve function, and was continuously released into the extracellular space in the presence of glucose and fell rapidly during aglycemia. Our findings indicated that glycogen is present in peripheral nerve, primarily in myelinating Schwann cells, and exclusively supports large-diameter, myelinated axon conduction during aglycemia. Available evidence suggests that peripheral nerve glycogen breaks down during aglycemia and is passed, probably as lactate, to myelinated axons to support function. Unmyelinated axons are not protected by glycogen and are more vulnerable to dysfunction during periods of hypoglycemia. . Copyright © 2012 American Neurological Association.

Schwann Cell Glycogen Selectively Supports Myelinated Axon Function

PubMed Central

Brown, Angus M; Evans, Richard D; Black, Joel; Ransom, Bruce R

2012-01-01

Objectives Interruption of energy supply to peripheral axons is a cause of axon loss. We determined if glycogen was present in mammalian peripheral nerve, and if it supported axon conduction during aglycemia. Methods We used biochemical assay and electron microscopy to determine the presence of glycogen, and electrophysiology to monitor axon function. Results Glycogen was present in sciatic nerve, its concentration varying directly with ambient [glucose]. Electron microscopy detected glycogen granules primarily in myelinating Schwann cell cytoplasm and these diminished after exposure to aglycemia. During aglycemia, conduction failure in large myelinated axons (A fibers) mirrored the time-course of glycogen loss. Latency to CAP failure was directly related to nerve glycogen content at aglycemia onset. Glycogen did not benefit the function of slow-conducting, small diameter unmyelinated axons (C fibers) during aglycemia. Blocking glycogen breakdown pharmacologically accelerated CAP failure during aglycemia in A fibers, but not in C fibers. Lactate was as effective as glucose in supporting sciatic nerve function, and was continuously released into the extracellular space in the presence of glucose and fell rapidly during aglycemia. Interpretation Our findings indicated that glycogen is present in peripheral nerve, primarily in myelinating Schwann cells, and exclusively supports large diameter, myelinated axon conduction during aglycemia. Available evidence suggests that peripheral nerve glycogen breaks down during aglycemia and is passed, probably as lactate, to myelinated axons to support function. Unmyelinated axons are not protected by glycogen and are more vulnerable to dysfunction during periods of hypoglycemia. PMID:23034913

Retinal nerve fiber layer in primary open-angle glaucoma with high myopia determined by optical coherence tomography and scanning laser polarimetry.

PubMed

Wang, Xiao-en; Wang, Xiao-yu; Gu, Yang-shun; Huang, Zhu

2013-01-01

Fundus changes associated with high myopia (HM) may mask those associated with primary open-angle glaucoma (POAG). This study aim to determine the characteristics of RNFL thickness changes in patients with both POAG and HM and compare these to changes in patients with only HM. The diagnostic capabilities of both OCT and GDxVCC in this subset of patients are also evaluated. Twenty-two eyes with POAG and HM (spherical equivalent (SE) between -6.0 and -12.0 D) were evaluated, and 22 eyes with HM were used for comparison. Characteristic retinal nerve fiber layer (RNFL) thickness profiles in patients with POAG and HM were examined using optical coherence tomography (OCT) and scanning laser polarimetry with variable corneal compensation (GDxVCC), and the diagnostic capabilities of these imaging modalities were compared. RNFL parameters evaluated included superior average (Savg-GDx), inferior average (Iavg-GDx), temporal-superior-nasal- inferior-temporal (TSNIT) average, and nerve fiber indicator (NFI) on GDxVCC and superior average (Savg-OCT), inferior average (Iavg-OCT), nasal average (Navg-OCT), temporal average (Tavg-OCT), and average thickness (AvgThick-OCT) on OCT (fast RNFL scan). Visual field testing was performed and defects were evaluated using mean defect (MD) and pattern standard deviation (PSD). The RNFL parameters (P < 0.05) significantly different between groups included Savg-GDx, Iavg-GDx, TSNIT average, NFI, Savg-OCT, Iavg-OCT, Tavg-OCT, and AvgThick-OCT. Significant correlations existed between TSNIT average and AvgThick-OCT (r = 0.778), TSNIT average and MD (r = 0.749), AvgThick-OCT and MD (r = 0.647), TSNIT average and PSD (r = -0.756), and AvgThick-OCT and PSD (r = -0.784). The area under the receiver operating characteristic curve (AUROC) values of TSNIT average, Savg-GDx, Iavg-GDx, NFI, Savg-OCT, Iavg-OCT, Navg-OCT, Tavg-OCT, and AvgThick-OCT were 0.947, 0.962, 0.973, 0.994, 0.909, 0.917, 0.511, 0.906, and 0.913, respectively. The NFI AUROC was the highest value. RNFL thickness was significantly lower in all but the nasal quadrant in patients with POAG and HM, compared to patients with only HM. Measurements with OCT and GDxVCC were well-correlated, and both modalities detected RNFL thickness changes. However, GDxVCC was better than OCT in detecting POAG in HM patients.

N-cadherin expression in palisade nerve endings of rat vellus hairs.

PubMed

Kaidoh, Toshiyuki; Inoué, Takao

2008-02-01

Palisade nerve endings (PNs) are mechanoreceptors around vellus hairs of mammals. Each lanceolate nerve ending (LN) of the PN is characterized by a sensory nerve ending symmetrically sandwiched by two processes of type II terminal Schwann cells (tSCIIs). However, the molecular mechanisms underlying the structural organization of the PN are poorly understood. Electron microscopy showed that adherens junctions appeared to adhere to the sensory nerve ending and tSCII processes, so we examined the location of the N-cadherin adhesion system in PNs of rat vellus hairs by using immunoelectron microscopy. N-cadherin localized near both ends of the cell boundary between sensory nerve ending and tSCII processes, which corresponded to the sites of adherens junctions. We further found cadherin-associated proteins, alpha- and beta-catenins, at the linings of adherens junctions. Three-dimensional reconstruction of immunoelectron microscopic serial thin sections showed four linear arrays of N-cadherin arranged longitudinally along the LN beneath the four longitudinal borders of two tSCII processes. In contrast, sensory nerve fibers just proximal to the LNs formed common unmyelinated nerve fibers, in which N-cadherin was located mainly at the mesaxon of type I terminal Schwann cells (tSCIs). These results suggest that the four linear arrays of N-cadherin-mediated junctions adhere the sensory nerve ending and tSCII processes side by side to form the characteristic structure of the LN, and the structural differences between the LNs and the proximal unmyelinated nerve fibers possibly are due to the difference in the pattern of N-cadherin expression between sensory nerve endings and tSCII or tSCI processes. (c) 2007 Wiley-Liss, Inc.

[Lipomatosis of nerve: a clinicopathologic analysis of 15 cases].

PubMed

MAO, Rong-jun; YANG, Ke-fei; WANG, Jian

2011-03-01

To study the clinicopathologic features of lipomatosis of nerve (NLS). The clinical, radiologic and pathologic features were analyzed in 15 cases of NLS. There were a total of 10 males and 5 females. The age of patients ranged from 4 to 42 years (mean age = 22.4 years). Eleven cases were located in the upper limbs and 4 cases in the lower limbs. The median nerve was the most common involved nerve. The patients typically presented before 30 years of age (often at birth or in early childhood) with a soft and slowly enlarging mass in the limb, with or without accompanying motor and sensory deficits. Some cases also had macrodactyly and carpal tunnel syndrome. MRI showed the presence of fatty tissue between nerve fascicles, resembling coaxial cable in axial plane and assuming a spaghetti-like appearance in coronal plane. On gross examination, the affected nerve was markedly increased in length and diameter. It consisted of a diffusely enlarged greyish-yellow lobulated fusiform beaded mass within the epineural sheath. Histologically, the epineurium was infiltrated by fibrofatty tissue which separated, surrounded and compressed the usually normal-appearing nerve fascicles, resulting in perineural septation of nerve fascicles and microfascicle formation. The infiltration sometimes resulted in concentric arrangement of perineural cells and pseudo-onion bulb-like hypertrophic changes. The perineurial cells might proliferate, with thickening of collagen fibers, degeneration and atrophic changes of nerve bundles. Immunohistochemical study showed that the nerve fibers expressed S-100 protein, neurofilament and CD56 (weak). The endothelial cells and dendritic fibers were highlighted by CD34. The intravascular smooth muscle cells were positive for muscle-specific actin. NLS is a rare benign soft tissue tumor of peripheral nerve. The MRI findings are characteristic. A definitive diagnosis can be made with histologic examination of tissue biopsy.

Continuous-wave optical stimulation of the rat prostate nerves using an all-single-mode 1455 nm diode laser and fiber system

NASA Astrophysics Data System (ADS)

Tozburun, Serhat; Lagoda, Gwen A.; Burnett, Arthur L.; Fried, Nathaniel M.

2011-03-01

Optical nerve stimulation (ONS) has recently been reported as a potential alternative to electrical nerve stimulation. Continuous-wave (CW) laser stimulation of the prostate cavernous nerves (CN) in a rat model, in vivo, has also been demonstrated in our previous studies. The objective of this study is to present a new all-single-mode-fiber configuration for ONS with the laser operating in CW mode for potential diagnostic applications. An infrared pigtailed single-mode diode laser (λ = 1455 nm) was used in this study for noncontact ONS. This new all-fiber approach introduces several advantages including: (1) a less expensive and more compact ONS system, (2) elimination of alignment of optical components, and (3) an improved spatial beam profile. Successful optical stimulation of the rat CN using this new design was observed after the CN reached a threshold temperature of ~ 41 °C with response times as short as 3 s. Upon further study, this configuration may be useful for identification and preservation of the cavernous nerves during prostate cancer surgery.

Detection of Progressive Retinal Nerve Fiber Layer Loss in Glaucoma Using Scanning Laser Polarimetry with Variable Corneal Compensation

PubMed Central

Medeiros, Felipe A.; Alencar, Luciana M.; Zangwill, Linda M.; Bowd, Christopher; Vizzeri, Gianmarco; Sample, Pamela A.; Weinreb, Robert N.

2010-01-01

Purpose To evaluate the ability of scanning laser polarimetry with variable corneal compensation to detect progressive retinal nerve fiber layer (RNFL) loss in glaucoma patients and patients suspected of having the disease. Methods This was an observational cohort study that included 335 eyes of 195 patients. Images were obtained annually with the GDx VCC scanning laser polarimeter, along with optic disc stereophotographs and standard automated perimetry (SAP) visual fields. The median follow-up time was 3.94 years. Progression was determined using commercial software for SAP and by masked assessment of optic disc stereophotographs performed by expert graders. Random coefficient models were used to evaluate the relationship between RNFL thickness measurements over time and progression as determined by SAP and/or stereophotographs. Results From the 335 eyes, 34 (10%) showed progression over time by stereophotographs and/or SAP. Average GDx VCC measurements decreased significantly over time for both progressors as well as non-progressors. However, the rate of decline was significantly higher in the progressing group (−0.70 μm/year) compared to the non-progressing group (−0.14 μm/year; P = 0.001). Black race and male sex were significantly associated with higher rates of RNFL loss during follow-up. Conclusions The GDx VCC scanning laser polarimeter was able to identify longitudinal RNFL loss in eyes that showed progression in optic disc stereophotographs and/or visual fields. These findings suggest that this technology could be useful to detect and monitor progressive disease in patients with established diagnosis of glaucoma or suspected of having the disease. PMID:19029038

Evaluation of Interocular Retinal Nerve Fiber Layer Thickness Symmetry as a Diagnostic Modality for Glaucoma.

PubMed

Hong, Seung Woo; Lee, Seung Bum; Jee, Dong-Hyun; Ahn, Myung Douk

2016-09-01

The purpose of study was to measure the diagnostic utility of interocular retinal nerve fiber layer (RNFL) symmetry and interocular RNFL thickness comparison. Both eyes of 103 normal subjects and 106 glaucoma patients (31 patients with early glaucoma and 75 patients with moderate to severe glaucoma) received comprehensive ophthalmologic evaluation including visual field testing and optic disc scanning using optical coherence tomography. RNFL thickness values for 256 measurement points were rearranged according to a new reference line connecting the optic disc center and the foveola. The interocular RNFL thickness symmetry value and absolute and fractional interocular difference in RNFL thickness were calculated and compared between groups. Area under the receiver operating characteristic curves (AUROCs) were calculated and compared. Among the parameters reflecting whole RNFL status, the corrected interocular RNFL thickness symmetry exhibited the largest AUROCs at all glaucoma stages. RNFL thickness and absolute and fractional interocular difference in RNFL thickness exhibited largest AUROC in the inferotemporal area, regardless of glaucoma stage. In the early glaucoma group, absolute and fractional interocular RNFL thickness differences in the temporal and superotemporal areas exhibited equal to or larger AUROCs than RNFL thickness. The AUROCs for RNFL thickness were greater than those for absolute and fractional interocular RNFL thickness differences in the moderate to severe glaucoma group except in the nasal and temporal area. The corrected interocular RNFL thickness symmetry value is an effective diagnostic tool for glaucoma. Interocular comparison of RNFL thickness has good diagnostic performance and gives information about the RNFL beyond just the RNFL thickness itself.

Evaluation of the Ganglion Cell Complex and Retinal Nerve Fiber Layer in Low, Moderate, and High Myopia: A Study by RTVue Spectral Domain Optical Coherence Tomography.

PubMed

Sezgin Akcay, Betul Ilkay; Gunay, Betul Onal; Kardes, Esra; Unlu, Cihan; Ergin, Ahmet

2017-01-01

To assess the effect of low, moderate, and high myopia on the thickness of the retinal nerve fiber layer (RNFL) and Ganglion cell complex (GCC) measured by Spectral Domain Optical Coherence Tomography (SD-OCT) in non-glaucomatous subjects. The subjects were divided into three groups: low (n = 81, 35.6%), moderate (n = 79, 34.8%), and highly myopic eyes (n = 67, 29.5%). The RNFL thickness profile, including the average, superior, nasal, inferior, and temporal quadrant and each of the eight directional thicknesses, was measured. GCC parameters, including the average, superior, and inferior values, the focal loss volume (FLV), and the global loss volume (GLV), were measured. The correlation between the OCT measurements and the axial length was evaluated. The average, superior, inferior, and nasal RNFL thicknesses of low and moderate myopic eyes were found to be significantly higher than those of highly myopic eyes. The temporal RNFL thicknesses were not different among the three groups. The average, superior, and inferior ganglion cell complex values of low and moderate myopic eyes were significantly higher than those of highly myopic eyes. The FLV and GLV of low and moderate myopic eyes were significantly higher than those of highly myopic eyes (p = 0.001 for all). In the moderate and high myopia groups, the average RNFL thickness and GCC thickness were both negatively correlated with the axial length. Highly myopic subjects tend to have thinner RNFL and GCC thicknesses than subjects with low and moderate myopia.

Retinal nerve fiber layer thickness map and blood flow pulsation measured with SDOCT

NASA Astrophysics Data System (ADS)

Mujat, Mircea; Chan, Raymond C.; Cense, Barry; Pierce, Mark; Park, Hyle; Joo, Chulmin; Chen, Teresa C.; de Boer, Johannes F.

2006-02-01

Spectral-Domain Optical Coherence Tomography (SDOCT) allows for in-vivo video-rate investigation of biomedical tissue depth structure intended for non-invasive optical diagnostics. It has been suggested that OCT can be used for di-agnosis of glaucoma by measuring the thickness of the Retinal Nerve Fiber Layer (RNLF). We present an automated method for determining the RNFL thickness from a 3-D dataset based on edge detection using a deformable spline algo-rithm. The RNFL thickness map is combined with an integrated reflectance map and retinal cross-sectional images to provide the ophthalmologist with a familiar image for interpreting the OCT data. The video-rate capabilities of our SDOCT system allow for mapping the true retinal topography since motion artifacts are significantly reduced as com-pared to slower time-domain systems. Combined with Doppler Velocimetry, SDOCT also provides information on retinal blood flow dynamics. We analyzed the pulsatile nature of the bidirectional flow dynamics in an artery-vein pair for a healthy volunteer at different locations and for different blood vessel diameters. The Doppler phase shift is determined as the phase difference at the same point of adjacent depth profiles, and is integrated over the area delimited by two circles corresponding to the blood vessels location. Its temporal evolution clearly shows the blood flow pulsatile nature, the cardiac cycle, in both artery and vein. The artery is identified as having a stronger variation of the integrated phase shift. We observe that artery pulsation is always easily detectable, while vein pulsation seems to depend on the veins diameter.

Abnormal retinal nerve fiber layer thickness and macula lutea in patients with mild cognitive impairment and Alzheimer's disease.

PubMed

Gao, LiYan; Liu, Ying; Li, XiaoHong; Bai, QuanHao; Liu, Ping

2015-01-01

We investigated possible abnormalities in the retinal nerve fiber layer (RNFL) and macula lutea of patients diagnosed with Alzheimer's disease (AD) and mild cognitive impairment (MCI) and tested for any correlation with the severity of dementia. A total of 72 subjects, comprising 25 AD patients, 26 MCI patients and 21 healthy individuals (controls) were enrolled in this study. The thickness of the RNFL and volume of the macula lutea was determined using optical coherence tomography (OCT). When compared with controls, we found statistically significant thinning of the RNFL in AD patients at all clock-hour positions except 12:00, and nasal quadrant, 2:00, 3:00 and 4:00. After adjusting several risk factors, the average thickness of the RNFL was reduced in MCI patients compared to AD patients, with specific reductions at inferior quadrant, 5:00 and 6:00. Compared to controls, MCI patients showed a significant decrease in RNFL thickness only in the temporal quadrant, 8:00, 9:00 and 10:00. We found significant reduction in the volume of the macula lutea both in AD and MCI patients. Finally, we could not establish any correlation between patient Mini-Mental State Examination (MMSE) scores (an estimation of the severity of cognitive impairment) and any OCT parameter. Retinal degeneration in AD and MCI patients results in decreased thickness of the RNFL, and reduced macular volume in AD and MCI patients. However, there seems to be no correlation between these changes and the severity of dementia. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Impact of anatomical parameters on optical coherence tomography retinal nerve fiber layer thickness abnormality patterns

NASA Astrophysics Data System (ADS)

Baniasadi, Neda; Wang, Mengyu; Wang, Hui; Jin, Qingying; Mahd, Mufeed; Elze, Tobias

2017-02-01

Purpose: To evaluate the effects of four anatomical parameters (angle between superior and inferior temporal retinal arteries [inter-artery angle, IAA], optic disc [OD] rotation, retinal curvature, and central retinal vessel trunk entry point location [CRVTL]) on retinal nerve fiber layer thickness (RNFLT) abnormality marks by OCT machines. Methods: Cirrus OCT circumpapillary RNFLT measurements and Humphrey visual fields (HVF 24-2) of 421 patients from a large glaucoma clinic were included. Ellipses were fitted to the OD borders. Ellipse rotation relative to the vertical axis defined OD rotation. CRVTL was manually marked on the horizontal axis of the ellipse on the OCT fundus image. IAA was calculated between manually marked retinal artery locations at the 1.73mm radius around OD. Retinal curvature was determined by the inner limiting membrane on the horizontal B-scan closest to the OD center. For each location on the circumpapillary scanning area, logistic regression was used to determine if each of the four parameters had a significant impact on RNFLT abnormality marks independent of disease severity. The results are presented on spatial maps of the entire scanning area. Results: Variations in IAA significantly influenced abnormality marks on 38.8% of the total scanning area, followed by CRVTL (19.2%) and retinal curvature (18.7%). The effect of OD rotation was negligible (<1%). Conclusions: A natural variation in IAA, retinal curvature, and CRVTL can affect OCT abnormality ratings, which may bias clinical diagnosis. Our spatial maps may help OCT manufacturers to introduce location specific norms to ensure that abnormality marks indicate ocular disease instead of variations in eye anatomy.

Glaucomatous retinal nerve fiber layer thickness loss is associated with slower reaction times under a divided attention task.

PubMed

Tatham, Andrew J; Boer, Erwin R; Rosen, Peter N; Della Penna, Mauro; Meira-Freitas, Daniel; Weinreb, Robert N; Zangwill, Linda M; Medeiros, Felipe A

2014-11-01

To examine the relationship between glaucomatous structural damage and ability to divide attention during simulated driving. Cross-sectional observational study. Hamilton Glaucoma Center, University of California San Diego. Total of 158 subjects from the Diagnostic Innovations in Glaucoma Study, including 82 with glaucoma and 76 similarly aged controls. Ability to divide attention was investigated by measuring reaction times to peripheral stimuli (at low, medium, or high contrast) while concomitantly performing a central driving task (car following or curve negotiation). All subjects had standard automated perimetry (SAP) and optical coherence tomography was used to measure retinal nerve fiber layer (RNFL) thickness. Cognitive ability was assessed using the Montreal Cognitive Assessment and subjects completed a driving history questionnaire. Reaction times to the driving simulator divided attention task. The mean reaction times to the low-contrast stimulus were 1.05 s and 0.64 s in glaucoma and controls, respectively, during curve negotiation (P < .001), and 1.19 s and 0.77 s (P = .025), respectively, during car following. There was a nonlinear relationship between reaction times and RNFL thickness in the better eye. RNFL thickness remained significantly associated with reaction times even after adjusting for age, SAP mean deviation in the better eye, cognitive ability, and central driving task performance. Although worse SAP sensitivity was associated with worse ability to divide attention, RNFL thickness measurements provided additional information. Information from structural tests may improve our ability to determine which patients are likely to have problems performing daily activities, such as driving. Copyright © 2014 Elsevier Inc. All rights reserved.

Correlation of Retinal Nerve Fiber Layer Thickness and Visual Fields in Glaucoma: A broken stick model

PubMed Central

Alasil, Tarek; Wang, Kaidi; Yu, Fei; Field, Matthew G.; Lee, Hang; Baniasadi, Neda; de Boer, Johannes F.; Coleman, Anne L.; Chen, Teresa C.

2015-01-01

Purpose To determine the retinal nerve fiber layer (RNFL) thickness at which visual field (VF) damage becomes detectable and associated with structural loss. Design Retrospective cross-sectional study. Methods Eighty seven healthy and 108 glaucoma subjects (one eye per subject) were recruited from an academic institution. All patients had VF examinations (Swedish Interactive Threshold Algorithm 24-2 test of the Humphrey visual field analyzer 750i; Carl Zeiss Meditec, Dublin, CA) and spectral domain optical coherence tomography RNFL scans (Spectralis, Heidelberg Engineering, Heidelberg, Germany). Comparison of RNFL thicknesses values with VF threshold values showed a plateau of VF threshold values at high RNFL thickness values and then a sharp decrease at lower RNFL thickness values. A broken stick statistical analysis was utilized to estimate the tipping point at which RNFL thickness values are associated with VF defects. The slope for the association between structure and function was computed for data above and below the tipping point. Results The mean RNFL thickness value that was associated with initial VF loss was 89 μm. The superior RNFL thickness value that was associated with initial corresponding inferior VF loss was 100 μm. The inferior RNFL thickness value that was associated with initial corresponding superior VF loss was 73 μm. The differences between all the slopes above and below the aforementioned tipping points were statistically significant (p<0.001). Conclusions In open angle glaucoma, substantial RNFL thinning or structural loss appears to be necessary before functional visual field defects become detectable. PMID:24487047

Structural parameters associated with location of peaks of peripapillary retinal nerve fiber layer thickness in young healthy eyes.

PubMed

Yamashita, Takehiro; Asaoka, Ryo; Kii, Yuya; Terasaki, Hiroto; Murata, Hiroshi; Sakamoto, Taiji

2017-01-01

The location of the peaks of the circumpapillary retinal nerve fiber layer (cpRNFL) thickness is affected by several ocular parameters. In this study, we have generated equations that can determine the peaks of the cpRNFL. This study was a prospective, observational, cross sectional study of 118 healthy right eyes. The axial length, optic disc tilt, superiortemporal (ST)- and inferiortemporal (IT)-peaks of the cpRNFL thickness, and angles of the ST and IT retinal arteries (RA) and veins (RV) were determined. The correlations between the location of the ST- and IT-peaks and ocular structural parameters and the sex, body height and weight were calculated. The best fit equations to generate the location of the ST/IT-peaks were determined using corrected-Akaike Information Criteria. The location of the ST-peak was 0.72+(0.40 x ST-RA)+(0.27 x ST-RV)+(0.14 x height)-(0.47 x papillo-macular-position)-(0.11 x disc tilt) with a coefficient of correlation of 0.61 (P<0.0001). The location of the IT-peak was 21.88+(0.53 x IT-RA)+(0.15 x IT-RV)+(0.041 x corneal thickness)-(1.00 x axial length) with a coefficient of correlation of 0.59 (P<0.0001). The location of ST/IT peaks is determined by different parameters of the ocular structure. These equations allow clinicians to obtain an accurate location of the peaks for a more accurate diagnosis of glaucoma.

Specific Location of Disc Hemorrhage is Linked to Nerve Fiber Layer Defects.

PubMed

Yoo, Young Cheol; Kim, Joon Mo; Park, Han Seok; Yoo, Chungkwon; Shim, Seong Hee; Won, Yu Sam; Park, Ki Ho; Chang, Robert T

2017-06-01

To investigate the relationship between retinal nerve fiber layer (RNFL) defects and the quadrant and proximal location of disc hemorrhages (DHs) in a large population examined for health screening. A total of 168,044 subjects older than 20 years underwent a single screening ophthalmic examination with color fundus photography as part of a comprehensive health screening program. The presence and location of DHs and RNFL defects were assessed. The DH locations were defined according to the quadrant location (inferotemporal, superotemporal, inferonasal, or superonasal) and the most proximal end of DHs relative to the disc center (cup base, cup margin, disc rim, or extrapapillary region). Using these two location descriptors as independent variables, a logistic regression analysis was conducted to explore the effects of DH location on RNFL defects. Two hundred twenty-six eyes had DH and 120 (53.1%) of them had RNFL defects. After adjusting for proximal location, DHs located in the inferotemporal quadrant accompanied RFNL defects 12 times more frequently than those in the superonasal quadrant (odds ratio [OR], 11.81; P = .004). Conversely, after adjusting for quadrant location, the ORs for an associated RNFL defect were 3.73 (P < .001), 16.54 (P < .001), and 8.91 (P = .002) for DHs with the proximal end at the disc rim, cup margin, and cup base, respectively. Among the four quadrants and four proximal locations, DHs were identified most frequently in the inferotemporal quadrant and outside the disc, respectively. Some DH locations, such as the inferotemporal quadrant and the cup margin, were associated with RNFL defects, whereas others were not.

Chronic low-frequency stimulation transforms cat masticatory muscle fibers into jaw-slow fibers.

PubMed

Kang, Lucia H D; Hoh, Joseph F Y

2011-09-01

Cat masticatory muscle during regeneration expresses masticatory-specific myofibrillar proteins upon innervation by a fast muscle nerve but acquires the jaw-slow phenotype when innervated by a slow muscle nerve. Here, we test the hypothesis that chronic low-frequency stimulation simulating impulses from the slow nerve can result in masticatory-to-slow fiber-type transformation. In six cats, the temporalis muscle was continuously stimulated directly at 10 Hz for up to 12 weeks using a stimulator affixed to the skull. Stimulated muscles were analyzed by immunohistochemistry using, among others, monoclonal antibodies against masticatory-specific myosin heavy chain (MyHC), myosin binding protein-C, and tropomyosins. Under the electrodes, stimulation induced muscle regeneration, which generated slow fibers. Deep to the electrodes, at two to three weeks, two distinct populations of masticatory fibers began to express slow MyHC: 1) evenly distributed fibers that completely suppressed masticatory-specific proteins but transiently co-expressed fetal MyHCs, and 2) incompletely transformed fibers that express slow and masticatory but not fetal MyHCs. SDS-PAGE confirmed de novo expression of slow MyHC and β-tropomyosin in the stimulated muscles. We conclude that chronic low-frequency stimulation induces masticatory-to-slow fiber-type conversion. The two populations of transforming masticatory fibers may differ in their mode of activation or lineage of their myogenic cells.

Nerve-dependent changes in skeletal muscle myosin heavy chain after experimental denervation and cross-reinnervation and in a demyelinating mouse model of Charcot-Marie-Tooth disease type 1A.

PubMed

Maggs, Alison M; Huxley, Clare; Hughes, Simon M

2008-12-01

Innervation regulates the contractile properties of vertebrate muscle fibers, in part through the effect of electrical activity on expression of distinct myosins. Herein we analyze the role of innervation in regulating the accumulation of the general, maturational, and adult forms of rodent slow myosin heavy chain (MyHC) that are defined by the presence of distinct antigenic epitopes. Denervation increases the number of fibers that express general slow MyHC, but it decreases the adult slow MyHC epitope. Cross-reinnervation of slow muscle by a fast nerve leads to an increase in the number of fibers that express fast MyHC. In both cases, there is an increase in the number of fibers that express slow and fast IIA MyHCs, but without the adult slow MyHC epitope. The data suggest that innervation is required for maturation and maintenance of diversity of both slow and fast fibers. The sequence of slow MyHC epitope transitions is a useful biomarker, and it may play a significant role during nerve-dependent changes in muscle fiber function. We applied this detailed muscle analysis to a transgenic mouse model of human motor and sensory neuropathy IA, also known as Charcot-Marie-Tooth disease type 1A (CMT1A), in which electrical conduction in some motor nerves is poor due to demyelination. The mice display atrophy of some muscle fibers and changes in slow and fast MyHC epitope expression, suggestive of a progressive increase in innervation of muscle fibers by fast motor neurons, even at early stages. The potential role of these early changes in disease pathogenesis is assessed.

Tomographic Structural Changes of Retinal Layers after Internal Limiting Membrane Peeling for Macular Hole Surgery.

PubMed

Faria, Mun Yueh; Ferreira, Nuno P; Cristóvao, Diana M; Mano, Sofia; Sousa, David Cordeiro; Monteiro-Grillo, Manuel

2018-01-01

To highlight tomographic structural changes of retinal layers after internal limiting membrane (ILM) peeling in macular hole surgery. Nonrandomized prospective, interventional study in 38 eyes (34 patients) subjected to pars plana vitrectomy and ILM peeling for idiopathic macular hole. Retinal layers were assessed in nasal and temporal regions before and 6 months after surgery using spectral domain optical coherence tomography. Total retinal thickness increased in the nasal region and decreased in the temporal region. The retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL) showed thinning on both nasal and temporal sides of the fovea. The thickness of the outer plexiform layer (OPL) increased. The outer nuclear layer (ONL) and outer retinal layers (ORL) increased in thickness after surgery in both nasal and temporal regions. ILM peeling is associated with important alterations in the inner retinal layer architecture, with thinning of the RNFL-GCL-IPL complex and thickening of OPL, ONL, and ORL. These structural alterations can help explain functional outcome and could give indications regarding the extent of ILM peeling, even though peeling seems important for higher rate of hole closure. © 2017 S. Karger AG, Basel.

The Effect of Exercise on Neuropathic Symptoms, Nerve Function, and Cutaneous Innervation in People with Diabetic Peripheral Neuropathy

PubMed Central

Kluding, Patricia M.; Pasnoor, Mamatha; Singh, Rupali; Jernigan, Stephen; Farmer, Kevin; Rucker, Jason; Sharma, Neena; Wright, Douglas E.

2012-01-01

Although exercise can significantly reduce the prevalence and severity of diabetic complications, no studies have evaluated the impact of exercise on nerve function in people with diagnosed diabetic peripheral neuropathy (DPN). The purpose of this pilot study was to examine feasibility and effectiveness of a supervised, moderately intense aerobic and resistance exercise program in people with DPN. We hypothesize that the exercise intervention can improve neuropathic symptoms, nerve function, and cutaneous innervation. Methods A pre-test post-test design was to assess change in outcome measures following participation in a 10-week aerobic and strengthening exercise program. Seventeen subjects with diagnosed DPN (8 males/9 females; age 58.4±5.98; duration of diabetes 12.4±12.2 years) completed the study. Outcome measures included pain measures (visual analog scale), Michigan Neuropathy Screening Instrument (MNSI) questionnaire of neuropathic symptoms, nerve function measures, and intraepidermal nerve fiber (IENF) density and branching in distal and proximal lower extremity skin biopsies. Results Significant reductions in pain (−18.1±35.5 mm on a 100 mm scale, p=0.05), neuropathic symptoms (−1.24±1.8 on MNSI, p=0.01), and increased intraepidermal nerve fiber branching (+0.11±0.15 branch nodes/fiber, p=−.008) from a proximal skin biopsy were noted following the intervention. Conclusions This is the first study to describe improvements in neuropathic and cutaneous nerve fiber branching following supervised exercise in people with diabetic peripheral neuropathy. These findings are particularly promising given the short duration of the intervention, but need to be validated by comparison with a control group in future studies. PMID:22717465

The effect of exercise on neuropathic symptoms, nerve function, and cutaneous innervation in people with diabetic peripheral neuropathy.

PubMed

Kluding, Patricia M; Pasnoor, Mamatha; Singh, Rupali; Jernigan, Stephen; Farmer, Kevin; Rucker, Jason; Sharma, Neena K; Wright, Douglas E

2012-01-01

Although exercise can significantly reduce the prevalence and severity of diabetic complications, no studies have evaluated the impact of exercise on nerve function in people with diagnosed diabetic peripheral neuropathy (DPN). The purpose of this pilot study was to examine feasibility and effectiveness of a supervised, moderately intense aerobic and resistance exercise program in people with DPN. We hypothesized that the exercise intervention can improve neuropathic symptoms, nerve function, and cutaneous innervation. A pre-test post-test design was used to assess change in outcome measures following participation in a 10-week aerobic and strengthening exercise program. Seventeen subjects with diagnosed DPN (8 males/9 females; age 58.4±5.98; duration of diabetes 12.4±12.2 years) completed the study. Outcome measures included pain measures (visual analog scale), Michigan Neuropathy Screening Instrument (MNSI) questionnaire of neuropathic symptoms, nerve function measures, and intraepidermal nerve fiber (IENF) density and branching in distal and proximal lower extremity skin biopsies. Significant reductions in pain (-18.1±35.5 mm on a 100 mm scale, P=.05), neuropathic symptoms (-1.24±1.8 on MNSI, P=.01), and increased intraepidermal nerve fiber branching (+0.11±0.15 branch nodes/fiber, P=.008) from a proximal skin biopsy were noted following the intervention. This is the first study to describe improvements in neuropathic and cutaneous nerve fiber branching following supervised exercise in people with diabetic peripheral neuropathy. These findings are particularly promising given the short duration of the intervention, but need to be validated by comparison with a control group in future studies. Copyright © 2012 Elsevier Inc. All rights reserved.

Value of a novel PGA-collagen tube on recurrent laryngeal nerve regeneration in a rat model.

PubMed

Suzuki, Hiroshi; Araki, Koji; Matsui, Toshiyasu; Tomifuji, Masayuki; Yamashita, Taku; Kobayashi, Yasushi; Shiotani, Akihiro

2016-07-01

Nerbridge (Toyobo Co., Ltd., Osaka, Japan) is a novel polyglycolic acid (PGA) tube that is filled with collagen fibers and that facilitates nerve fiber expansion and blood vessel growth. It is biocompatible and commercially available, with governmental approval for practical use in Japan. We hypothesized that the PGA-collagen tube would promote regeneration of the recurrent laryngeal nerve (RLN). This hypothesis was examined in a rat axotomy model of the RLN. Prospective animal study. The axotomy model was established by transection of the left RLN in adult Sprague-Dawley rats. The cut ends of the nerve were bridged using Nerbridge (Toyobo Co., Ltd.) with a 1-mm gap (tube-treatment group) or direct sutures (sutured-control group). Left vocal fold mobility, nerve conduction velocity, morphology, and histology were assessed after 15 weeks. Fifteen weeks after treatment, nerve fiber connections were observed macroscopically in both groups, and more clear myelinated fibers and better prevention of laryngeal muscle atrophy were observed in the tube-treatment group compared with the sutured-control group. However, vocal fold movement recovery was not observed in either group, and the conduction velocity of the RLN did not differ between the two groups. Better nerve regeneration was observed in the tube-treatment group. The combination therapy with molecular or gene therapy might be an effective strategy to improve vocal fold movement. The PGA-collagen tube has the potential to promote regeneration of the RLN and to be a scaffold for drug administration in these combination therapies. N/A. Laryngoscope, 126:E233-E239, 2016. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Modeling the action-potential-sensitive nonlinear-optical response of myelinated nerve fibers and short-term memory

NASA Astrophysics Data System (ADS)

Shneider, M. N.; Voronin, A. A.; Zheltikov, A. M.

2011-11-01

The Goldman-Albus treatment of the action-potential dynamics is combined with a phenomenological description of molecular hyperpolarizabilities into a closed-form model of the action-potential-sensitive second-harmonic response of myelinated nerve fibers with nodes of Ranvier. This response is shown to be sensitive to nerve demyelination, thus enabling an optical diagnosis of various demyelinating diseases, including multiple sclerosis. The model is applied to examine the nonlinear-optical response of a three-neuron reverberating circuit—the basic element of short-term memory.

Engineering Bi-Layer Nanofibrous Conduits for Peripheral Nerve Regeneration

PubMed Central

Zhu, Yiqian; Wang, Aijun; Patel, Shyam; Kurpinski, Kyle; Diao, Edward; Bao, Xuan; Kwong, George; Young, William L.

2011-01-01

Trauma injuries often cause peripheral nerve damage and disability. A goal in neural tissue engineering is to develop synthetic nerve conduits for peripheral nerve regeneration having therapeutic efficacy comparable to that of autografts. Nanofibrous conduits with aligned nanofibers have been shown to promote nerve regeneration, but current fabrication methods rely on rolling a fibrous sheet into the shape of a conduit, which results in a graft with inconsistent size and a discontinuous joint or seam. In addition, the long-term effects of nanofibrous nerve conduits, in comparison with autografts, are still unknown. Here we developed a novel one-step electrospinning process and, for the first time, fabricated a seamless bi-layer nanofibrous nerve conduit: the luminal layer having longitudinally aligned nanofibers to promote nerve regeneration, and the outer layer having randomly organized nanofibers for mechanical support. Long-term in vivo studies demonstrated that bi-layer aligned nanofibrous nerve conduits were superior to random nanofibrous conduits and had comparable therapeutic effects to autografts for nerve regeneration. In summary, we showed that the engineered nanostructure had a significant impact on neural tissue regeneration in situ. The results from this study will also lead to the scalable fabrication of engineered nanofibrous nerve conduits with designed nanostructure. This technology platform can be combined with drug delivery and cell therapies for tissue engineering. PMID:21501089

Scanning laser polarimetry in glaucoma

PubMed Central

Dada, Tanuj; Sharma, Reetika; Angmo, Dewang; Sinha, Gautam; Bhartiya, Shibal; Mishra, Sanjay K; Panda, Anita; Sihota, Ramanjit

2014-01-01

Glaucoma is an acquired progressive optic neuropathy which is characterized by changes in the optic nerve head and retinal nerve fiber layer (RNFL). White-on-white perimetry is the gold standard for the diagnosis of glaucoma. However, it can detect defects in the visual field only after the loss of as many as 40% of the ganglion cells. Hence, the measurement of RNFL thickness has come up. Optical coherence tomography and scanning laser polarimetry (SLP) are the techniques that utilize the evaluation of RNFL for the evaluation of glaucoma. SLP provides RNFL thickness measurements based upon the birefringence of the retinal ganglion cell axons. We have reviewed the published literature on the use of SLP in glaucoma. This review elucidates the technological principles, recent developments and the role of SLP in the diagnosis and monitoring of glaucomatous optic neuropathy, in the light of scientific evidence so far. PMID:25494244

Scanning laser polarimetry in glaucoma.

PubMed

Dada, Tanuj; Sharma, Reetika; Angmo, Dewang; Sinha, Gautam; Bhartiya, Shibal; Mishra, Sanjay K; Panda, Anita; Sihota, Ramanjit

2014-11-01

Glaucoma is an acquired progressive optic neuropathy which is characterized by changes in the optic nerve head and retinal nerve fiber layer (RNFL). White-on-white perimetry is the gold standard for the diagnosis of glaucoma. However, it can detect defects in the visual field only after the loss of as many as 40% of the ganglion cells. Hence, the measurement of RNFL thickness has come up. Optical coherence tomography and scanning laser polarimetry (SLP) are the techniques that utilize the evaluation of RNFL for the evaluation of glaucoma. SLP provides RNFL thickness measurements based upon the birefringence of the retinal ganglion cell axons. We have reviewed the published literature on the use of SLP in glaucoma. This review elucidates the technological principles, recent developments and the role of SLP in the diagnosis and monitoring of glaucomatous optic neuropathy, in the light of scientific evidence so far.

Immunohistologic analysis of spontaneous recurrent laryngeal nerve reinnervation in a rat model.

PubMed

Rosko, Andrew J; Kupfer, Robbi A; Oh, Sang S; Haring, Catherine T; Feldman, Eva L; Hogikyan, Norman D

2018-03-01

After recurrent laryngeal nerve injury (RLN), spontaneous reinnervation of the larynx occurs with input from multiple sources. The purpose of this study was to determine the timing and efficiency of reinnervation across a resected RLN segment in a rat model of RLN injury. Animal study. Twelve male 60-day-old Sprague Dawley rats underwent resection of a 5-mm segment of the right RLN. Rats were sacrificed at 1, 2, 4, and 12 weeks after nerve injury to harvest the larynx and trachea for immunohistologic analysis. The distal RLN segment was stained with neurofilament, and axons were counted and compared to the nonoperated side. Thyroarytenoid (TA) muscles were stained with alpha-bungarotoxin, synaptophysin, and neurofilament to identify intact neuromuscular junctions (NMJ). The number of intact NMJs from the denervated side was compared to the nonoperated side. Nerve fibers regenerated across the resected RLN gap into the distal recurrent laryngeal nerve to innervate the TA muscle. The number of nerve fibers in the distal nerve segment increased over time and reached the normal number by 12 weeks postdenervation. Axons formed intact neuromuscular junctions in the TA, with 48.8% ± 16.7% of the normal number of intact NMJs at 4 weeks and 88.3% ± 30.1% of the normal number by 12 weeks. Following resection of an RLN segment in a rat model, nerve fibers spontaneously regenerate through the distal segment of the transected nerve and form intact NMJs in order to reinnervate the TA muscle. NA. Laryngoscope, 128:E117-E122, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Benefits of Ilizarov automated bone distraction for nerves and articular cartilage in experimental leg lengthening.

PubMed

Shchudlo, Nathalia; Varsegova, Tatyana; Stupina, Tatyana; Shchudlo, Michael; Saifutdinov, Marat; Yemanov, Andrey

2017-09-18

To determine peculiarities of tissue responses to manual and automated Ilizarov bone distraction in nerves and articular cartilage. Twenty-nine dogs were divided in two experimental groups: Group M - leg lengthening with manual distraction (1 mm/d in 4 steps), Group A - automated distraction (1 mm/d in 60 steps) and intact group. Animals were euthanized at the end of distraction, at 30 th day of fixation in apparatus and 30 d after the fixator removal. M-responses in gastrocnemius and tibialis anterior muscles were recorded, numerical histology of peroneal and tibialis nerves and knee cartilage semi-thin sections, scanning electron microscopy and X-ray electron probe microanalysis were performed. Better restoration of M-response amplitudes in leg muscles was noted in A-group. Fibrosis of epineurium with adipocytes loss in peroneal nerve, subperineurial edema and fibrosis of endoneurium in some fascicles of both nerves were noted only in M-group, shares of nerve fibers with atrophic and degenerative changes were bigger in M-group than in A-group. At the end of experiment morphometric parameters of nerve fibers in peroneal nerve were comparable with intact nerve only in A-group. Quantitative parameters of articular cartilage (thickness, volumetric densities of chondrocytes, percentages of isogenic clusters and empty cellular lacunas, contents of sulfur and calcium) were badly changed in M-group and less changed in A-group. Automated Ilizarov distraction is more safe method of orthopedic leg lengthening than manual distraction in points of nervous fibers survival and articular cartilage arthrotic changes.

Benefits of Ilizarov automated bone distraction for nerves and articular cartilage in experimental leg lengthening

PubMed Central

Shchudlo, Nathalia; Varsegova, Tatyana; Stupina, Tatyana; Shchudlo, Michael; Saifutdinov, Marat; Yemanov, Andrey

2017-01-01

AIM To determine peculiarities of tissue responses to manual and automated Ilizarov bone distraction in nerves and articular cartilage. METHODS Twenty-nine dogs were divided in two experimental groups: Group M - leg lengthening with manual distraction (1 mm/d in 4 steps), Group A - automated distraction (1 mm/d in 60 steps) and intact group. Animals were euthanized at the end of distraction, at 30th day of fixation in apparatus and 30 d after the fixator removal. M-responses in gastrocnemius and tibialis anterior muscles were recorded, numerical histology of peroneal and tibialis nerves and knee cartilage semi-thin sections, scanning electron microscopy and X-ray electron probe microanalysis were performed. RESULTS Better restoration of M-response amplitudes in leg muscles was noted in A-group. Fibrosis of epineurium with adipocytes loss in peroneal nerve, subperineurial edema and fibrosis of endoneurium in some fascicles of both nerves were noted only in M-group, shares of nerve fibers with atrophic and degenerative changes were bigger in M-group than in A-group. At the end of experiment morphometric parameters of nerve fibers in peroneal nerve were comparable with intact nerve only in A-group. Quantitative parameters of articular cartilage (thickness, volumetric densities of chondrocytes, percentages of isogenic clusters and empty cellular lacunas, contents of sulfur and calcium) were badly changed in M-group and less changed in A-group. CONCLUSION Automated Ilizarov distraction is more safe method of orthopedic leg lengthening than manual distraction in points of nervous fibers survival and articular cartilage arthrotic changes. PMID:28979852

ROLE OF TIMING IN ASSESSMENT OF NERVE REGENERATION

PubMed Central

BRENNER, MICHAEL J.; MORADZADEH, ARASH; MYCKATYN, TERENCE M.; TUNG, THOMAS H. H.; MENDEZ, ALLEN B.; HUNTER, DANIEL A.; MACKINNON, SUSAN E.

2014-01-01

Small animal models are indispensable for research on nerve injury and reconstruction, but their superlative regenerative potential may confound experimental interpretation. This study investigated time-dependent neuroregenerative phenomena in rodents. Forty-six Lewis rats were randomized to three nerve allograft groups treated with 2 mg/(kg day) tacrolimus; 5 mg/(kg day) Cyclosporine A; or placebo injection. Nerves were subjected to histomorphometric and walking track analysis at serial time points. Tacrolimus increased fiber density, percent neural tissue, and nerve fiber count and accelerated functional recovery at 40 days, but these differences were undetectable by 70 days. Serial walking track analysis showed a similar pattern of recovery. A ‘blow-through’ effect is observed in rodents whereby an advancing nerve front overcomes an experimental defect given sufficient time, rendering experimental groups indistinguishable at late time points. Selection of validated time points and corroboration in higher animal models are essential prerequisites for the clinical application of basic research on nerve regeneration. PMID:18381659

Functional role of peripheral opioid receptors in the regulation of cardiac spinal afferent nerve activity during myocardial ischemia

PubMed Central

Longhurst, John C.

2013-01-01

Thinly myelinated Aδ-fiber and unmyelinated C-fiber cardiac sympathetic (spinal) sensory nerve fibers are activated during myocardial ischemia to transmit the sensation of angina pectoris. Although recent observations showed that myocardial ischemia increases the concentrations of opioid peptides and that the stimulation of peripheral opioid receptors inhibits chemically induced visceral and somatic nociception, the role of opioids in cardiac spinal afferent signaling during myocardial ischemia has not been studied. The present study tested the hypothesis that peripheral opioid receptors modulate cardiac spinal afferent nerve activity during myocardial ischemia by suppressing the responses of cardiac afferent nerve to ischemic mediators like bradykinin and extracellular ATP. The nerve activity of single unit cardiac afferents was recorded from the left sympathetic chain (T2–T5) in anesthetized cats. Forty-three ischemically sensitive afferent nerves (conduction velocity: 0.32–3.90 m/s) with receptive fields in the left and right ventricles were identified. The responses of these afferent nerves to repeat ischemia or ischemic mediators were further studied in the following protocols. First, epicardial administration of naloxone (8 μmol), a nonselective opioid receptor antagonist, enhanced the responses of eight cardiac afferent nerves to recurrent myocardial ischemia by 62%, whereas epicardial application of vehicle (PBS) did not alter the responses of seven other cardiac afferent nerves to ischemia. Second, naloxone applied to the epicardial surface facilitated the responses of seven cardiac afferent nerves to epicardial ATP by 76%. Third, administration of naloxone enhanced the responses of seven other afferent nerves to bradykinin by 85%. In contrast, in the absence of naloxone, cardiac afferent nerves consistently responded to repeated application of ATP (n = 7) or bradykinin (n = 7). These data suggest that peripheral opioid peptides suppress the responses of cardiac sympathetic afferent nerves to myocardial ischemia and ischemic mediators like ATP and bradykinin. PMID:23645463

ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density.

PubMed

Dahan, Albert; Dunne, Ann; Swartjes, Maarten; Proto, Paolo L; Heij, Lara; Vogels, Oscar; van Velzen, Monique; Sarton, Elise; Niesters, Marieke; Tannemaat, Martijn R; Cerami, Anthony; Brines, Michael

2013-11-08

Small nerve fiber loss and damage (SNFLD) is a frequent complication of sarcoidosis that is associated with autonomic dysfunction and sensory abnormalities, including pain syndromes that severely degrade the quality of life. SNFLD is hypothesized to arise from the effects of immune dysregulation, an essential feature of sarcoidosis, on the peripheral and central nervous systems. Current therapy of sarcoidosis-associated SNFLD consists primarily of immune suppression and symptomatic treatment; however, this treatment is typically unsatisfactory. ARA 290 is a small peptide engineered to activate the innate repair receptor that antagonizes inflammatory processes and stimulates tissue repair. Here we show in a blinded, placebo-controlled trial that 28 d of daily subcutaneous administration of ARA 290 in a group of patients with documented SNFLD significantly improves neuropathic symptoms. In addition to improved patient-reported symptom-based outcomes, ARA 290 administration was also associated with a significant increase in corneal small nerve fiber density, changes in cutaneous temperature sensitivity, and an increased exercise capacity as assessed by the 6-minute walk test. On the basis of these results and of prior studies, ARA 290 is a potential disease-modifying agent for treatment of sarcoidosis-associated SNFLD.

ARA 290 Improves Symptoms in Patients with Sarcoidosis-Associated Small Nerve Fiber Loss and Increases Corneal Nerve Fiber Density

PubMed Central

Dahan, Albert; Dunne, Ann; Swartjes, Maarten; Proto, Paolo L; Heij, Lara; Vogels, Oscar; van Velzen, Monique; Sarton, Elise; Niesters, Marieke; Tannemaat, Martijn R; Cerami, Anthony; Brines, Michael

2013-01-01

Small nerve fiber loss and damage (SNFLD) is a frequent complication of sarcoidosis that is associated with autonomic dysfunction and sensory abnormalities, including pain syndromes that severely degrade the quality of life. SNFLD is hypothesized to arise from the effects of immune dysregulation, an essential feature of sarcoidosis, on the peripheral and central nervous systems. Current therapy of sarcoidosis-associated SNFLD consists primarily of immune suppression and symptomatic treatment; however, this treatment is typically unsatisfactory. ARA 290 is a small peptide engineered to activate the innate repair receptor that antagonizes inflammatory processes and stimulates tissue repair. Here we show in a blinded, placebo-controlled trial that 28 d of daily subcutaneous administration of ARA 290 in a group of patients with documented SNFLD significantly improves neuropathic symptoms. In addition to improved patient-reported symptom-based outcomes, ARA 290 administration was also associated with a significant increase in corneal small nerve fiber density, changes in cutaneous temperature sensitivity, and an increased exercise capacity as assessed by the 6-minute walk test. On the basis of these results and of prior studies, ARA 290 is a potential disease-modifying agent for treatment of sarcoidosis-associated SNFLD. PMID:24136731

Poly(D,L-Lactide-Co-Glycolide) Tubes With Multifilament Chitosan Yarn or Chitosan Sponge Core in Nerve Regeneration.

PubMed

Wlaszczuk, Adam; Marcol, Wiesław; Kucharska, Magdalena; Wawro, Dariusz; Palen, Piotr; Lewin-Kowalik, Joanna

2016-11-01

The influence of different kinds of nerve guidance conduits on regeneration of totally transected rat sciatic nerves through a 7-mm gap was examined. Five different types of conduits made of chitosan and poly(D,L-lactide-co-glycolide) (PLGA) were constructed and tested in vivo. We divided 50 animals into equal groups of 10, with a different type of conduit implanted in each group: chitosan sponge core with an average molecular mass of polymer (Mv) of 287 kDa with 7 channels in a PLGA sleeve, chitosan sponge core with an Mv of 423 kDa with 7 channels in a PLGA sleeve, chitosan sponge core (Mv, 423 kDa) with 13 channels in a PLGA sleeve, chitosan multifilament yarn in a PLGA sleeve, and a PLGA sleeve only. Seven weeks after the operation, we examined the distance covered by regenerating nerve fibers, growing of nerves into the conduit's core, and intensity and type of inflammatory reaction in the conduit, as well as autotomy behavior (reflecting neuropathic pain intensity) in the animals. Two types of conduits were allowing nerve outgrowth through the gap with minor autotomy and minor inflammatory reactions. These were the conduits with chitosan multifilament yarn in a PLGA sleeve and the conduits with 13-channel microcrystalline chitosan sponge in a PLGA sleeve. The type of chitosan used to build the nerve guidance conduit influences the intensity and character of inflammatory reaction present during nerve regeneration, which in turn affects the distance crossed by regenerating nerve fibers, growing of the nerve fibers into the conduit's core, and the intensity of autotomy in the animals. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Extraocular Muscles in Patients With Infantile Nystagmus

PubMed Central

Berg, Kathleen T.; Hunter, David G.; Bothun, Erick D.; Antunes-Foschini, Rosalia; McLoon, Linda K.

2013-01-01

Objective To test the hypothesis that the extraocular muscles (EOMs) of patients with infantile nystagmus have muscular and innervational adaptations that may have a role in the involuntary oscillations of the eyes. Methods Specimens of EOMs from 10 patients with infantile nystagmus and postmortem specimens from 10 control subjects were prepared for histologic examination. The following variables were quantified: mean myofiber cross-sectional area, myofiber central nucleation, myelinated nerve density, nerve fiber density, and neuromuscular junction density. Results In contrast to control EOMs, infantile nystagmus EOMs had significantly more centrally nucleated myofibers, consistent with cycles of degeneration and regeneration. The EOMs of patients with nystagmus also had a greater degree of heterogeneity in myofiber size than did those of controls, with no difference in mean myofiber cross-sectional area. Mean myelinated nerve density, nerve fiber density, and neuromuscular junction density were also significantly decreased in infantile nystagmus EOMs. Conclusions The EOMs of patients with infantile nystagmus displayed a distinct hypoinnervated phenotype. This represents the first quantification of changes in central nucleation and myofiber size heterogeneity, as well as decreased myelinated nerve, nerve fiber, and neuromuscular junction density. These results suggest that deficits in motor innervation are a potential basis for the primary loss of motor control. Clinical Relevance Improved understanding of the etiology of nystagmus may direct future diagnostic and treatment strategies. PMID:22411664

Optical Coherence Tomography as a Biomarker for Diagnosis, Progression, and Prognosis of Neurodegenerative Diseases

PubMed Central

Otin, Sofia; Fuertes, Maria I.; Vilades, Elisa; Gracia, Hector; Ara, Jose R.; Alarcia, Raquel; Polo, Vicente; Larrosa, Jose M.; Pablo, Luis E.

2016-01-01

Neurodegenerative diseases present a current challenge for accurate diagnosis and for providing precise prognostic information. Developing imaging biomarkers for multiple sclerosis (MS), Parkinson disease (PD), and Alzheimer's disease (AD) will improve the clinical management of these patients and may be useful for monitoring treatment effectiveness. Recent research using optical coherence tomography (OCT) has demonstrated that parameters provided by this technology may be used as potential biomarkers for MS, PD, and AD. Retinal thinning has been observed in these patients and new segmentation software for the analysis of the different retinal layers may provide accurate information on disease progression and prognosis. In this review we analyze the application of retinal evaluation using OCT technology to provide better understanding of the possible role of the retinal layers thickness as biomarker for the detection of these neurodegenerative pathologies. Current OCT analysis of the retinal nerve fiber layer and, specially, the ganglion cell layer thickness may be considered as a good biomarker for disease diagnosis, severity, and progression. PMID:27840739

Neuroanatomy of the Pig Cardiac Ventricles. A Stereomicroscopic, Confocal and Electron Microscope Study.

PubMed

Pauziene, Neringa; Rysevaite-Kyguoliene, Kristina; Alaburda, Paulius; Pauza, Audrys G; Skukauskaite, Monika; Masaityte, Aiste; Laucaityte, Goda; Saburkina, Inga; Inokaitis, Hermanas; Plisiene, Jurgita; Pauza, Dainius H

2017-10-01

Although the pig is a model for heart disease, the neuroanatomy of cardiac ventricles (CV) in this species remains undetailed. We aimed to define the innervation pattern of pig CV, combining histochemistry for acetylcholinesterase, immunofluorescent labeling and electron microscopy. Forty nine examined pig hearts show that the major nerves supplying the ventral side of CV descend from the venous part of the heart hilum. Fewer in number and smaller in size, epicardial nerves supply the dorsal half of the CV. Epicardial nerves on the left ventricle are thicker than those on the right. Ventricular ganglia of various sizes distribute at the basal level of both CV. Averagely, we found 3,848 ventricular neuronal somata per heart. The majority of somata were cholinergic, although ganglionic cells of different neurochemical phenotypes (positive for nNOS, ChAT/nNOS, or ChAT/TH) were also observed. Large and most numerous nerves proceeded within the epicardium. Most of endocardium and myocardium contained a network of nerve bundles and nerve fibers (NFs). But, a large number of thin nerves extended along the bundle of His and its branches. The majority of NFs were adrenergic, while cholinergic NFs were scarce yet more abundant than nitrergic ones. Sensory NFs positive for CGRP were the second most abundant phenotype after adrenergic NFs in all layers of the ventricular wall. Electron microscopy elucidated that ultrastructure of nerves varied between different areas of CV. The described structural organization of CV provides an anatomical basis for further functional and pathophysiological studies in the pig heart. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 300:1756-1780, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Extracellular Recording of Light Responses from Optic Nerve Fibers and the Caudal Photoreceptor in the Crayfish

PubMed Central

Nesbit, Steven C.; Van Hoof, Alexander G.; Le, Chi C.; Dearworth, James R.

2015-01-01

Few laboratory exercises have been developed using the crayfish as a model for teaching how neural processing is done by sensory organs that detect light stimuli. This article describes the dissection procedures and methods for conducting extracellular recording from light responses of both the optic nerve fibers found in the animal’s eyestalk and from the caudal photoreceptor located in the ventral nerve cord. Instruction for ADInstruments’ data acquisition system is also featured for the data collection and analysis of responses. The comparison provides students a unique view on how spike activities measured from neurons code image-forming and non-image-forming processes. Results from the exercise show longer latency and lower frequency of firing by the caudal photoreceptor compared to optic nerve fibers to demonstrate evidence of different functions. After students learn the dissection, recording procedure, and the functional anatomy, they can develop their own experiments to learn more about the photoreceptive mechanisms and the sensory integration of modalities by these light-responsive interneurons. PMID:26557793

Acute Effect of Pore-Forming Clostridium perfringens ε-Toxin on Compound Action Potentials of Optic Nerve of Mouse.

PubMed

Cases, Mercè; Llobet, Artur; Terni, Beatrice; Gómez de Aranda, Inmaculada; Blanch, Marta; Doohan, Briain; Revill, Alexander; Brown, Angus M; Blasi, Juan; Solsona, Carles

2017-01-01

ε-Toxin is a pore forming toxin produced by Clostridium perfringens types B and D. It is synthesized as a less active prototoxin form that becomes fully active upon proteolytic activation. The toxin produces highly lethal enterotoxaemia in ruminants, has the ability to cross the blood-brain barrier (BBB) and specifically binds to myelinated fibers. We discovered that the toxin induced a release of ATP from isolated mice optic nerves, which are composed of myelinated fibers that are extended from the central nervous system. We also investigated the effect of the toxin on compound action potentials (CAPs) in isolated mice optic nerves. When nerves were stimulated at 100 Hz during 200 ms, the decrease of the amplitude and the area of the CAPs was attenuated in the presence of ε-toxin. The computational modelling of myelinated fibers of mouse optic nerve revealed that the experimental results can be mimicked by an increase of the conductance of myelin and agrees with the pore forming activity of the toxin which binds to myelin and could drill it by making pores. The intimate ultrastructure of myelin was not modified during the periods of time investigated. In summary, the acute action of the toxin produces a subtle functional impact on the propagation of the nerve action potential in myelinated fibers of the central nervous system with an eventual desynchronization of the information. These results may agree with the hypothesis that the toxin could be an environmental trigger of multiple sclerosis (MS).

Acute Effect of Pore-Forming Clostridium perfringens ε-Toxin on Compound Action Potentials of Optic Nerve of Mouse

PubMed Central

Terni, Beatrice; Gómez de Aranda, Inmaculada; Blanch, Marta; Brown, Angus M.

2017-01-01

ε-Toxin is a pore forming toxin produced by Clostridium perfringens types B and D. It is synthesized as a less active prototoxin form that becomes fully active upon proteolytic activation. The toxin produces highly lethal enterotoxaemia in ruminants, has the ability to cross the blood–brain barrier (BBB) and specifically binds to myelinated fibers. We discovered that the toxin induced a release of ATP from isolated mice optic nerves, which are composed of myelinated fibers that are extended from the central nervous system. We also investigated the effect of the toxin on compound action potentials (CAPs) in isolated mice optic nerves. When nerves were stimulated at 100 Hz during 200 ms, the decrease of the amplitude and the area of the CAPs was attenuated in the presence of ε-toxin. The computational modelling of myelinated fibers of mouse optic nerve revealed that the experimental results can be mimicked by an increase of the conductance of myelin and agrees with the pore forming activity of the toxin which binds to myelin and could drill it by making pores. The intimate ultrastructure of myelin was not modified during the periods of time investigated. In summary, the acute action of the toxin produces a subtle functional impact on the propagation of the nerve action potential in myelinated fibers of the central nervous system with an eventual desynchronization of the information. These results may agree with the hypothesis that the toxin could be an environmental trigger of multiple sclerosis (MS). PMID:28798954

Neura, nerves, nerve fibers, neurofibrils, microtubules: multidimensional routes of pain, pleasure, and voluntary action in images across the ages.

PubMed

Frixione, Eugenio

2013-01-01

Available records indicate that the human body has always been conceived, in different periods and cultures, as spanned by multiple channels for internal communication and coherent functioning as a unit-"meridians" in treatises of Chinese medicine, metu in Egyptian papyri, srotas in Ayurvedic Indian texts, and neura in the Western scientific heritage from ancient Greece. Unfortunately, the earliest extant figurative depictions of such pathways of general control, complementary to the blood vessels, are late medieval copies of old crude sketches that attempted to show the main anatomico-physiological systems. The scarcity of adequate illustrations was more than compensated in the Renaissance, when the efforts of both artists and anatomists for the first time produced basically correct renditions of the human nervous system and many other bodily structures. As attention was next focused on microscopic structure as a requisite to understand physiological mechanisms, during the Enlightenment the nerves were revealed to consist of numerous thin tubes or fibers aligned in parallel. Improved microscopy techniques in the nineteenth century led to discovering and delineating still finer fibrils coursing along the cores of the nerve fibers themselves. Electron microscopy, developed throughout the twentieth century, recognized some of these fibrils within nerve fibers as being also tubular. All the progressive stages in understanding nerve construction, at increasingly more detailed scales, have been accompanied by technological advances and by debate about the structure and function relationship. And every step has been a source of amazing imagery. © 2013 Elsevier B.V. All rights reserved.

Quantitative RNFL attenuation coefficient measurements by RPE-normalized OCT data

NASA Astrophysics Data System (ADS)

Vermeer, K. A.; van der Schoot, J.; Lemij, H. G.; de Boer, J. F.

2012-03-01

We demonstrate significantly different scattering coefficients of the retinal nerve fiber layer (RNFL) between normal and glaucoma subjects. In clinical care, SD-OCT is routinely used to assess the RNFL thickness for glaucoma management. In this way, the full OCT data set is conveniently reduced to an easy to interpret output, matching results from older (non- OCT) instruments. However, OCT provides more data, such as the signal strength itself, which is due to backscattering in the retinal layers. For quantitative analysis, this signal should be normalized to adjust for local differences in the intensity of the beam that reaches the retina. In this paper, we introduce a model that relates the OCT signal to the attenuation coefficient of the tissue. The average RNFL signal (within an A-line) was then normalized based on the observed RPE signal, resulting in normalized RNFL attenuation coefficient maps. These maps showed local defects matching those found in thickness data. The average (normalized) RNFL attenuation coefficient of a fixed band around the optic nerve head was significantly lower in glaucomatous eyes than in normal eyes (3.0mm-1 vs. 4.9mm-1, P<0.01, Mann-Whitney test).

Small fiber neuropathy is a common feature of Ehlers-Danlos syndromes

PubMed Central

Cazzato, Daniele; Castori, Marco; Lombardi, Raffaella; Caravello, Francesca; Bella, Eleonora Dalla; Petrucci, Antonio; Grammatico, Paola; Dordoni, Chiara; Colombi, Marina

2016-01-01

Objective: To investigate the involvement of small nerve fibers in Ehlers-Danlos syndrome (EDS). Methods: Patients diagnosed with EDS underwent clinical, neurophysiologic, and skin biopsy assessment. We recorded sensory symptoms and signs and evaluated presence and severity of neuropathic pain according to the Douleur Neuropathique 4 (DN4) and ID Pain questionnaires and the Numeric Rating Scale (NRS). Sensory action potential amplitude and conduction velocity of sural nerve was recorded. Skin biopsy was performed at distal leg and intraepidermal nerve fiber density (IENFD) obtained and referred to published sex- and age-adjusted normative reference values. Results: Our cohort included 20 adults with joint hypermobility syndrome/hypermobility EDS, 3 patients with vascular EDS, and 1 patient with classic EDS. All except one patient had neuropathic pain according to DN4 and ID Pain questionnaires and reported 7 or more symptoms at the Small Fiber Neuropathy Symptoms Inventory Questionnaire. Pain intensity was moderate (NRS ≥4 and <7) in 8 patients and severe (NRS ≥7) in 11 patients. Sural nerve conduction study was normal in all patients. All patients showed a decrease of IENFD consistent with the diagnosis of small fiber neuropathy (SFN), regardless of the EDS type. Conclusions: SFN is a common feature in adults with EDS. Skin biopsy could be considered an additional diagnostic tool to investigate pain manifestations in EDS. PMID:27306637

Wavelength scanning digital interference holography for high-resolution ophthalmic imaging

NASA Astrophysics Data System (ADS)

Potcoava, Mariana C.; Kim, M. K.; Kay, Christine N.

2009-02-01

An improved digital interference holography (DIH) technique suitable for fundus images is proposed. This technique incorporates a dispersion compensation algorithm to compensate for the unknown axial length of the eye. Using this instrument we acquired successfully tomographic fundus images in human eye with narrow axial resolution less than 5μm. The optic nerve head together with the surrounding retinal vasculature were constructed. We were able to quantify a depth of 84μm between the retinal fiber and the retinal pigmented epithelium layers. DIH provides high resolution 3D information which could potentially aid in guiding glaucoma diagnosis and treatment.

Morphofunctional analysis of experimental model of esophageal achalasia in rats.

PubMed

Sabirov, A G; Raginov, I S; Burmistrov, M V; Chelyshev, Y A; Khasanov, R Sh; Moroshek, A A; Grigoriev, P N; Zefirov, A L; Mukhamedyarov, M A

2010-10-01

We carried out a detailed analysis of rat model of esophageal achalasia previously developed by us. Manifest morphological and functional disorders were observed in experimental achalasia: hyperplasia of the squamous epithelium, reduced number of nerve fibers, excessive growth of fibrous connective tissue in the esophageal wall, high contractile activity of the lower esophageal sphincter, and reduced motility of the longitudinal muscle layer. Changes in rat esophagus observed in experimental achalasia largely correlate with those in esophageal achalasia in humans. Hence, our experimental model can be used for the development of new methods of disease treatment.

A Deep Learning Approach to Digitally Stain Optical Coherence Tomography Images of the Optic Nerve Head.

PubMed

Devalla, Sripad Krishna; Chin, Khai Sing; Mari, Jean-Martial; Tun, Tin A; Strouthidis, Nicholas G; Aung, Tin; Thiéry, Alexandre H; Girard, Michaël J A

2018-01-01

To develop a deep learning approach to digitally stain optical coherence tomography (OCT) images of the optic nerve head (ONH). A horizontal B-scan was acquired through the center of the ONH using OCT (Spectralis) for one eye of each of 100 subjects (40 healthy and 60 glaucoma). All images were enhanced using adaptive compensation. A custom deep learning network was then designed and trained with the compensated images to digitally stain (i.e., highlight) six tissue layers of the ONH. The accuracy of our algorithm was assessed (against manual segmentations) using the dice coefficient, sensitivity, specificity, intersection over union (IU), and accuracy. We studied the effect of compensation, number of training images, and performance comparison between glaucoma and healthy subjects. For images it had not yet assessed, our algorithm was able to digitally stain the retinal nerve fiber layer + prelamina, the RPE, all other retinal layers, the choroid, and the peripapillary sclera and lamina cribrosa. For all tissues, the dice coefficient, sensitivity, specificity, IU, and accuracy (mean) were 0.84 ± 0.03, 0.92 ± 0.03, 0.99 ± 0.00, 0.89 ± 0.03, and 0.94 ± 0.02, respectively. Our algorithm performed significantly better when compensated images were used for training (P < 0.001). Besides offering a good reliability, digital staining also performed well on OCT images of both glaucoma and healthy individuals. Our deep learning algorithm can simultaneously stain the neural and connective tissues of the ONH, offering a framework to automatically measure multiple key structural parameters of the ONH that may be critical to improve glaucoma management.

Neuronal nitric oxide synthase in the olfactory system of an adult teleost fish Oreochromis mossambicus.

PubMed

Singru, Praful S; Sakharkar, Amul J; Subhedar, Nishikant

2003-07-11

The aim of the present study is to explore the distribution of nitric oxide synthase in the olfactory system of an adult teleost, Oreochromis mossambicus using neuronal nitric oxide synthase (nNOS) immunocytochemistry and nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) histochemistry methods. Intense nNOS immunoreactivity was noticed in several olfactory receptor neurons (ORNs), in their axonal extensions over the olfactory nerve and in some basal cells of the olfactory epithelium. nNOS containing fascicles of the ORNs enter the bulb from its rostral pole, spread in the olfactory nerve layer in the periphery of the bulb and display massive innervation of the olfactory glomeruli. Unilateral ablation of the olfactory organ resulted in dramatic loss of nNOS immunoreactivity in the olfactory nerve layer of the ipsilateral bulb. In the olfactory bulb of intact fish, some granule cells showed intense immunoreactivity; dendrites arising from the granule cells could be traced to the glomerular layer. Of particular interest is the occurrence of nNOS immunoreactivity in the ganglion cells of the nervus terminalis. nNOS containing fibers were also encountered in the medial olfactory tracts as they extend to the telencephalon. The NADPHd staining generally coincides with that of nNOS suggesting that it may serve as a marker for nNOS in the olfactory system of this fish. However, mismatch was encountered in the case of mitral cells, while all are nNOS-negative, few were NADPHd positive. The present study for the first time revealed the occurrence of nNOS immunoreactivity in the ORNs of an adult vertebrate and suggests a role for nitric oxide in the transduction of odor stimuli, regeneration of olfactory epithelium and processing of olfactory signals.

Innervation of taste buds revealed with Brainbow-labeling in mouse.

PubMed

Zaidi, Faisal N; Cicchini, Vanessa; Kaufman, Daniel; Ko, Elizabeth; Ko, Abraham; Van Tassel, Heather; Whitehead, Mark C

2016-12-01

Nerve fibers that surround and innervate the taste bud were visualized with inherent fluorescence using Brainbow transgenic mice that were generated by mating the founder line L with nestin-cre mice. Multicolor fluorescence revealed perigemmal fibers as branched within the non-taste epithelium and ending in clusters of multiple rounded swellings surrounding the taste pore. Brainbow-labeling also revealed the morphology and branching pattern of single intragemmal fibers. These taste bud fibers frequently innervated both the peripheral bud, where immature gemmal cells are located, and the central bud, where mature, differentiated cells are located. The fibers typically bore preterminal and terminal swellings, growth cones with filopodia, swellings, and rounded retraction bulbs. These results establish an anatomical substrate for taste nerve fibers to contact and remodel among receptor cells at all stages of their differentiation, an interpretation that was supported by staining with GAP-43, a marker for growing fibers and growth cones. © 2016 Anatomical Society.

Speckle reduction during all-fiber common-path optical coherence tomography of the cavernous nerves

NASA Astrophysics Data System (ADS)

Chitchian, Shahab; Fiddy, Michael; Fried, Nathaniel M.

2009-02-01

Improvements in identification, imaging, and visualization of the cavernous nerves during prostate cancer surgery, which are responsible for erectile function, may improve nerve preservation and postoperative sexual potency. In this study, we use a rat prostate, ex vivo, to evaluate the feasibility of optical coherence tomography (OCT) as a diagnostic tool for real-time imaging and identification of the cavernous nerves. A novel OCT system based on an all single-mode fiber common-path interferometer-based scanning system is used for this purpose. A wavelet shrinkage denoising technique using Stein's unbiased risk estimator (SURE) algorithm to calculate a data-adaptive threshold is implemented for speckle noise reduction in the OCT image. The signal-to-noise ratio (SNR) was improved by 9 dB and the image quality metrics of the cavernous nerves also improved significantly.

A New Preparation Method for Anisotropic Silk Fibroin Nerve Guidance Conduits and Its Evaluation In Vitro and in a Rat Sciatic Nerve Defect Model

PubMed Central

Schuh, Christina; Halbweis, Robert; Pajer, Krisztián; Márton, Gábor; Hopf, Rudolf; Mosia, Shorena; Rünzler, Dominik; Redl, Heinz; Nógrádi, Antal; Hausner, Thomas

2015-01-01

Over the past decade, silk fibroin (SF) has been emergently used in peripheral nerve tissue engineering. Current approaches aiming at producing SF-based nerve guidance conduits (SF-NGCs) used dissolved silk based on either aqueous solutions or organic solvents. In this study, we describe a novel procedure to produce SF-NGCs: A braided tubular structure of raw Bombyx mori silk is subsequently processed with the ternary solvent CaCl2/H2O/ethanol, formic acid, and methanol to improve its mechanical and topographical characteristics. Topographically, the combination of the treatments results in a fusion of the outer single silk fibers to a closed layer with a thickness ranging from about 40 to 75 μm. In contrast to the outer wall, the inner lumen (not treated with processing solvents) still represents the braided structure of single fibers. Mechanical stability, elasticity, and kink characteristics were evaluated with a custom-made test system. The modification procedure described here drastically improved the elastic properties of our tubular raw scaffold, favoring its use as a NGC. A cell migration assay with NIH/3T3-fibroblasts revealed the impermeability of the SF-NGC wall for possible invading and scar-forming cells. Moreover, the potential of the SF-NGC to serve as a substratum for Schwann cells has been demonstrated by cytotoxicity tests and live-dead stainings of Schwann cells grown on the inner surface of the SF-NGC. In vivo, the SF-NGC was tested in a rat sciatic nerve injury model. In short-term in vivo studies, it was proved that SF-NGCs are not triggering host inflammatory reactions. After 12 weeks, we could demonstrate morphological and functional reinnervation of the distal targets. Filled with collagen, a higher number of axons could be found in the distal to the graft (1678±303), compared with the empty SF-NGC (1274±146). The novel SF-NGC presented here shows promising results for the treatment of peripheral nerve injuries. The modification of braided structures to adapt their mechanical and topographical characteristics may support the translation of SF-based scaffolds into the clinical setting. However, further improvements and the use of extracellular matrix molecules and Schwann cells are suggested to enable silk tube based conduits to bridge long-distance nerve gaps. PMID:25819471

Predictive Factors for Visual Field Conversion: Comparison of Scanning Laser Polarimetry and Optical Coherence Tomography.

PubMed

Diekmann, Theresa; Schrems-Hoesl, Laura M; Mardin, Christian Y; Laemmer, Robert; Horn, Folkert K; Kruse, Friedrich E; Schrems, Wolfgang A

2018-02-01

The purpose of this study was to compare the ability of scanning laser polarimetry (SLP) and spectral-domain optical coherence tomography (SD-OCT) to predict future visual field conversion of subjects with ocular hypertension and early glaucoma. All patients were recruited from the Erlangen glaucoma registry and examined using standard automated perimetry, 24-hour intraocular pressure profile, and optic disc photography. Peripapillary retinal nerve fiber layer thickness (RNFL) measurements were obtained by SLP (GDx-VCC) and SD-OCT (Spectralis OCT). Positive and negative predictive values (PPV, NPV) were calculated for morphologic parameters of SLP and SD-OCT. Kaplan-Meier survival curves were plotted and log-rank tests were performed to compare the survival distributions. Contingency tables and Venn-diagrams were calculated to compare the predictive ability. The study included 207 patients-75 with ocular hypertension, 85 with early glaucoma, and 47 controls. Median follow-up was 4.5 years. A total of 29 patients (14.0%) developed visual field conversion during follow-up. SLP temporal-inferior RNFL [0.667; 95% confidence interval (CI), 0.281-0.935] and SD-OCT temporal-inferior RNFL (0.571; 95% CI, 0.317-0.802) achieved the highest PPV; nerve fiber indicator (0.923; 95% CI, 0.876-0.957) and SD-OCT mean (0.898; 95% CI, 0.847-0.937) achieved the highest NPV of all investigated parameters. The Kaplan-Meier curves confirmed significantly higher survival for subjects within normal limits of measurements of both devices (P<0.001). Venn diagrams tested with McNemar test statistics showed no significant difference for PPV (P=0.219) or NPV (P=0.678). Both GDx-VCC and SD-OCT demonstrate comparable results in predicting future visual field conversion if taking typical scans for GDx-VCC. In addition, the likelihood ratios suggest that GDx-VCC's nerve fiber indicator<30 may be the most useful parameter to confirm future nonconversion. (http://www.ClinicalTrials.gov number, NTC00494923; Erlangen Glaucoma Registry).

Macular versus Retinal Nerve Fiber Layer Parameters for Diagnosing Manifest Glaucoma: A Systematic Review of Diagnostic Accuracy Studies.

PubMed

Oddone, Francesco; Lucenteforte, Ersilia; Michelessi, Manuele; Rizzo, Stanislao; Donati, Simone; Parravano, Mariacristina; Virgili, Gianni

2016-05-01

Macular parameters have been proposed as an alternative to retinal nerve fiber layer (RNFL) parameters to diagnose glaucoma. Comparing the diagnostic accuracy of macular parameters, specifically the ganglion cell complex (GCC) and ganglion cell inner plexiform layer (GCIPL), with the accuracy of RNFL parameters for detecting manifest glaucoma is important to guide clinical practice and future research. Studies using spectral domain optical coherence tomography (SD OCT) and reporting macular parameters were included if they allowed the extraction of accuracy data for diagnosing manifest glaucoma, as confirmed with automated perimetry or a clinician's optic nerve head (ONH) assessment. Cross-sectional cohort studies and case-control studies were included. The QUADAS 2 tool was used to assess methodological quality. Only direct comparisons of macular versus RNFL parameters (i.e., in the same study) were conducted. Summary sensitivity and specificity of each macular or RNFL parameter were reported, and the relative diagnostic odds ratio (DOR) was calculated in hierarchical summary receiver operating characteristic (HSROC) models to compare them. Thirty-four studies investigated macular parameters using RTVue OCT (Optovue Inc., Fremont, CA) (19 studies, 3094 subjects), Cirrus OCT (Carl Zeiss Meditec Inc., Dublin, CA) (14 studies, 2164 subjects), or 3D Topcon OCT (Topcon, Inc., Tokyo, Japan) (4 studies, 522 subjects). Thirty-two of these studies allowed comparisons between macular and RNFL parameters. Studies generally reported sensitivities at fixed specificities, more commonly 0.90 or 0.95, with sensitivities of most best-performing parameters between 0.65 and 0.75. For all OCT devices, compared with RNFL parameters, macular parameters were similarly or slightly less accurate for detecting glaucoma at the highest reported specificity, which was confirmed in analyses at the lowest specificity. Included studies suffered from limitations, especially the case-control study design, which is known to overestimate accuracy. However, this flaw is less relevant as a source of bias in direct comparisons conducted within studies. With the use of OCT, RNFL parameters are still preferable to macular parameters for diagnosing manifest glaucoma, but the differences are small. Because of high heterogeneity, direct comparative or randomized studies of OCT devices or OCT parameters and diagnostic strategies are essential. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Retinal degeneration in progressive supranuclear palsy measured by optical coherence tomography and scanning laser polarimetry.

PubMed

Stemplewitz, Birthe; Kromer, Robert; Vettorazzi, Eik; Hidding, Ute; Frings, Andreas; Buhmann, Carsten

2017-07-13

This cross-sectional study compared the retinal morphology between patients with progressive supranuclear palsy (PSP) and healthy controls. (The retinal nerve fiber layer (RNFL) around the optic disc and the retina in the macular area of 22 PSP patients and 151 controls were investigated by spectral domain optical coherence tomography (SD-OCT). Additionally, the RNFL and the nerve fiber index (NFI) were measured by scanning laser polarimetry (SLP). Results of RNFL measurements with SD-OCT and SLP were compared to assess diagnostic discriminatory power. Applying OCT, PSP patients showed a smaller RNFL thickness in the inferior nasal and inferior temporal areas. The macular volume and the thickness of the majority of macular sectors were reduced compared to controls. SLP data showed a thinner RNFL thickness and an increase in the NFI in PSP patients. Sensitivity and specificity to discriminate PSP patients from controls were higher applying SLP than SD-OCT. Retinal changes did not correlate with disease duration or severity in any OCT or SLP measurement. PSP seems to be associated with reduced thickness and volume of the macula and reduction of the RNFL, independent of disease duration or severity. Retinal imaging with SD-OCT and SLP might become an additional tool in PSP diagnosis.

Guidance of neurite outgrowth on aligned electrospun polypyrrole/poly(styrene-beta-isobutylene-beta-styrene) fiber platforms.

PubMed

Liu, Xiao; Chen, Jun; Gilmore, Kerry J; Higgins, Michael J; Liu, Yong; Wallace, Gordon G

2010-09-15

The purpose of this work was to investigate the potential biomedical application of novel aligned electrospun polypyrrole (PPy)/poly(styrene-beta-isobutylene-beta-styrene) (SIBS) fibers. After successfully aligning the electroactive PPy/SIBS fibers based on our modified electrospinning method, we demonstrated that neurite outgrowth from PC12 cells could be highly orientated parallel to the aligned PPy/SIBS fibers. Physical interactions between the nerve cells and PPy/SIBS fibers through filopodia "sensing" were observed using atomic force microscopy. These observations indicate a role of contact guidance as a mechanism for the observed alignment. This work highlights the capacity for electroactive PPy/SIBS fibers to support and guide nerve cell differentiation through topographic cues, which is a highly desirable characteristic in medical implants for neurological applications. (c) 2010 Wiley Periodicals, Inc.

Comparison of histopathological effects of perineural administration of bupivacaine and bupivacaine-dexmedetomidine in rat sciatic nerve.

PubMed

Memari, Elham; Hosseinian, Mohammad-Ali; Mirkheshti, Ali; Arhami-Dolatabadi, Ali; Mirabotalebi, Mojtaba; Khandaghy, Mohsen; Daneshbod, Yahya; Alizadeh, Leila; Shirian, Sadegh

2016-11-01

Injection of a variety of drugs such as local anesthetics (LAs) for peripheral nerve block has been shown to cause damage to peripheral nerves. Bupivacaine is a local anesthetic widely used in surgical procedures. The aim of this study was to evaluate the neurotoxicity of LAs including Bupivacaine and dexmedetomidine (DEX)-Bupivacaine on sciatic nerve tissue at histopathological level. In addition, we investigated whether perineural administration of DEX can attenuate Bupivacaine-induced neurotoxicity. Twenty adult Sprague Dawley rats received unilateral sciatic nerve blocks with either 0.2ml of 0.5% bupivacaine (n=8) or 0.5% bupivacaine plus 0.005% DEX (n=8) or normal saline (0.9%, as control group) (n=4) in the left hind extremity. Sciatic nerves were harvested at 14days post-injection and analyzed for nerve damage using ultrastructure and histopathologic analysis. Histopathology of sciatic nerve at day 14 post-injection showed a variable degree of neuronal injury associated with perineural inflammation in each treatment group and was classified as none or mild, intermediate or severe. Administration of both LAs resulted in a significant decrease in the total number of myelinated fibers per nerve (95% CI for group difference: Bupivacaine, P=0.001, DEX-Bupivacaine, P=0.036) compared to the saline control group. Animals that received these perineural local anesthetics (LAs) injections showed increased severity of injury compared to the control group. Animals in the DEX-Bupivacaine group had higher perineural inflammation and nerve damage than those of the saline control group and less than those of the Bupivacaine group at day 14 post-injection. Quantitatively, average total nerve fiber per nerve and average myelinated nerve fiber density in the injured region of the Bupivacaine-treated group was less than that of the DEX-Bupivacaine-treated group. LAs injection into the nerve causes peripheral nerve damage and remains an important clinical danger. Bupivacaine is associated with considerable histopathological changes, including edema of the perineurium and myelin degeneration with Wallerian degeneration, when injected perineurally. Perineural DEX added to a clinical concentration of bupivacaine attenuates the Bupivacaine-induced injuries. Copyright © 2016 Elsevier GmbH. All rights reserved.

Trigeminal Proprioception Evoked by Strong Stretching of the Mechanoreceptors in Müller's Muscle Induces Reflex Contraction of the Orbital Orbicularis Oculi Slow-Twitch Muscle Fibers.

PubMed

Matsuo, Kiyoshi; Ban, Ryokuya; Ban, Midori; Yuzuriha, Shunsuke

2014-01-01

The mixed orbicularis oculi muscle lacks an intramuscular proprioceptive system such as muscle spindles, to induce reflex contraction of its slow-twitch fibers. We evaluated whether the mechanoreceptors in Müller's muscle function as extrinsic mechanoreceptors to induce reflex contraction of the slow-twitch fibers of the orbicularis oculi in addition to those of the levator and frontalis muscles. We evaluated in patients with aponeurosis-disinserted blepharoptosis whether strong stretching of the mechanoreceptors in Müller's muscle from upgaze with unilateral lid load induced reflex contraction of the orbicularis oculi slow-twitch fibers and whether anesthesia of Müller's muscle precluded the contraction. We compared the electromyographic responses of the bilateral orbicularis oculi muscles to unilateral intraoperative direct stimulation of the trigeminal proprioceptive nerve with those to unilateral transcutaneous electrical stimulation of the supraorbital nerve. Upgaze with a unilateral 3-g lid load induced reflex contraction of the bilateral orbicularis oculi muscles with ipsilateral dominance. Anesthesia of Müller's muscle precluded the reflex contraction. The orbicularis oculi reflex evoked by stimulation of the trigeminal proprioceptive nerve differed from that by electrical stimulation of the supraorbital nerve in terms of the intensity of current required to induce the reflex, the absence of R1, and duration. The mechanoreceptors in Müller's muscle functions as an extramuscular proprioceptive system to induce reflex contraction of the orbital orbicularis oculi slow-twitch fibers. Whereas reflex contraction of the pretarsal orbicularis fast-twitch fibers functions in spontaneous or reflex blinking, that of the orbital orbicularis oculi slow-twitch fibers may factor in grimacing and blepharospasm.

Trigeminal Proprioception Evoked by Strong Stretching of the Mechanoreceptors in Müller's Muscle Induces Reflex Contraction of the Orbital Orbicularis Oculi Slow-Twitch Muscle Fibers

PubMed Central

Ban, Ryokuya; Ban, Midori; Yuzuriha, Shunsuke

2014-01-01

Objective: The mixed orbicularis oculi muscle lacks an intramuscular proprioceptive system such as muscle spindles, to induce reflex contraction of its slow-twitch fibers. We evaluated whether the mechanoreceptors in Müller's muscle function as extrinsic mechanoreceptors to induce reflex contraction of the slow-twitch fibers of the orbicularis oculi in addition to those of the levator and frontalis muscles. Methods: We evaluated in patients with aponeurosis-disinserted blepharoptosis whether strong stretching of the mechanoreceptors in Müller's muscle from upgaze with unilateral lid load induced reflex contraction of the orbicularis oculi slow-twitch fibers and whether anesthesia of Müller's muscle precluded the contraction. We compared the electromyographic responses of the bilateral orbicularis oculi muscles to unilateral intraoperative direct stimulation of the trigeminal proprioceptive nerve with those to unilateral transcutaneous electrical stimulation of the supraorbital nerve. Results: Upgaze with a unilateral 3-g lid load induced reflex contraction of the bilateral orbicularis oculi muscles with ipsilateral dominance. Anesthesia of Müller's muscle precluded the reflex contraction. The orbicularis oculi reflex evoked by stimulation of the trigeminal proprioceptive nerve differed from that by electrical stimulation of the supraorbital nerve in terms of the intensity of current required to induce the reflex, the absence of R1, and duration. Conclusions: The mechanoreceptors in Müller's muscle functions as an extramuscular proprioceptive system to induce reflex contraction of the orbital orbicularis oculi slow-twitch fibers. Whereas reflex contraction of the pretarsal orbicularis fast-twitch fibers functions in spontaneous or reflex blinking, that of the orbital orbicularis oculi slow-twitch fibers may factor in grimacing and blepharospasm. PMID:25210572

Quantitative comparison of disc rim color in optic nerve atrophy of compressive optic neuropathy and glaucomatous optic neuropathy.

PubMed

Nakano, Eri; Hata, Masayuki; Oishi, Akio; Miyamoto, Kazuaki; Uji, Akihito; Fujimoto, Masahiro; Miyata, Manabu; Yoshimura, Nagahisa

2016-08-01

The purpose was to investigate an objective and quantitative method to estimate the redness of the optic disc neuroretinal rim, and to determine the usefulness of this method to differentiate compressive optic neuropathy (CON) from glaucomatous optic neuropathy (GON). In our study there were 126 eyes: 40 with CON, 40 with normal tension glaucoma (NTG), and 46 normal eyes (NOR). Digital color fundus photographs were assessed for the redness of disc rim color using ImageJ software. We separately measured the intensity of red, green, and blue pixels from RGB images. Three disc color indices (DCIs), which indicate the redness intensity, were calculated through existing formulas. All three DCIs of CON were significantly smaller than those of NOR (P < 0.001). In addition, when compared with NTG, DCIs were also significantly smaller in CON (P < 0.05). A comparison of mild CON and mild NTG (mean deviation (MD) > -6 dB), in which the extent of retinal nerve fiber layer thinning is comparable, the DCIs of mild CON were significantly smaller than those of mild NTG (P < 0.05). In contrast, DCIs did not differ between moderate-to-severe stages of CON and NTG (MD ≤ -6 dB), though the retinal nerve fibers of CON were more severely damaged than those of NTG. To differentiate between mild CON and mild NTG, all AUROCs for the three DCIs were above 0.700. A quantitative and objective assessment of optic disc color was useful in differentiating early-stage CON from GON and NOR.

Structural complexes in the squid giant axon membrane sensitive to ionic concentrations and cardiac glycosides

PubMed Central

Villegas, GM; Villegas, J

1976-01-01

Giant nerve fibers of squid Sepioteuthis sepiodea were incubated for 10 min in artificial sea water (ASW) under control conditions, in the absence of various ions, and in the presence of cardiac glycosides. The nerve fibers were fixed in OsO(4) and embedded in Epon, and structural complexes along the axolemma were studied. These complexes consist of a portion of axolemma exhibiting a three-layered substructure, an undercoating of a dense material (approximately 0.1μm in length and approximately 70-170 A in thickness), and a narrowing to disappearance of the axon-Schwann cell interspace. In the controls, the incidence of complexes per 1,000μm of axon perimeter was about 137. This number decreased to 10-25 percent when magnesium was not present in the incubating media, whatever the calcium concentration (88, 44, or 0 mM). In the presence of magnesium, the number and structural features of the complexes were preserved, though the number decreased to 65 percent when high calcium was simultaneously present. The complexes were also modified and decreased to 26-32 percent by incubating the nerves in solutions having low concentrations of sodium and potassium. The adding of 10(-5) M ouabain or strophanthoside to normal ASW incubating solution decreased them to 20-40 percent. Due to their sensitivity to changes in external ionic concentrations and to the presence of cardiac glycosides, the complexes are proposed to represent the structural correlate of specialized sites for active ion transport, although other factors may be involved. PMID:1254642

Phosphodiesterase type 4 inhibition enhances nitric oxide- and hydrogen sulfide-mediated bladder neck inhibitory neurotransmission.

PubMed

Agis-Torres, Ángel; Recio, Paz; López-Oliva, María Elvira; Martínez, María Pilar; Barahona, María Victoria; Benedito, Sara; Bustamante, Salvador; Jiménez-Cidre, Miguel Ángel; García-Sacristán, Albino; Prieto, Dolores; Fernandes, Vítor S; Hernández, Medardo

2018-03-16

Nitric oxide (NO) and hydrogen sulfide (H 2 S) play a pivotal role in nerve-mediated relaxation of the bladder outflow region. In the bladder neck, a marked phosphodiesterase type 4 (PDE4) expression has also been described and PDE4 inhibitors, as rolipram, produce smooth muscle relaxation. This study investigates the role of PDE4 isoenzyme in bladder neck gaseous inhibitory neurotransmission. We used Western blot and double immunohistochemical staining for the detection of NPP4 (PDE4) and PDE4A and organ baths for isometric force recording to roflumilast and tadalafil, PDE4 and PDE5, respectively, inhibitors in pig and human samples. Endogenous H 2 S production measurement and electrical field stimulation (EFS) were also performed. A rich PDE4 and PDE4A expression was observed mainly limited to nerve fibers of the smooth muscle layer of both species. Moreover, roflumilast produced a much more potent smooth muscle relaxation than that induced by tadalafil. In porcine samples, H 2 S generation was diminished by H 2 S and NO synthase inhibition and augmented by roflumilast. Relaxations elicited by EFS were potentiated by roflumilast. These results suggest that PDE4, mainly PDE4A, is mostly located within nerve fibers of the pig and human bladder neck, where roflumilast produces a powerful smooth muscle relaxation. In pig, the fact that roflumilast increases endogenous H 2 S production and EFS-induced relaxations suggests a modulation of PDE4 on NO- and H 2 S-mediated inhibitory neurotransmission.

Macular Ganglion Cell and Retinal Nerve Fiber Layer Thickness in Children With Refractive Errors-An Optical Coherence Tomography Study.

PubMed

Goh, Jody P; Koh, Victor; Chan, Yiong Huak; Ngo, Cheryl

2017-07-01

To study the distribution of macular ganglion cell-inner plexiform layer (GC-IPL) thickness and peripapillary retinal nerve fiber layer (RNFL) thickness in children with refractive errors. Two hundred forty-three healthy eyes from 139 children with refractive error ranging from -10.00 to +5.00 D were recruited from the National University Hospital Eye Surgery outpatient clinic. After a comprehensive ocular examination, refraction, and axial length (AL) measurement (IOLMaster), macular GC-IPL and RNFL thickness values were obtained with a spectral domain Cirrus high definition optical coherence tomography system (Carl Zeiss Meditec Inc.). Only scans with signal strength of >6/10 were included. Correlation between variables was calculated using the Pearson correlation coefficient. A multivariate analysis using mixed models was done to adjust for confounders. The mean spherical equivalent refraction was -3.20±3.51 D and mean AL was 24.39±1.72 mm. Average, minimum, superior, and inferior GC-IPL were 82.59±6.29, 77.17±9.65, 83.68±6.96, and 81.64±6.70 μm, respectively. Average, superior, and inferior peripapillary RNFL were 99.00±11.45, 123.20±25.81, and 124.24±22.23 μm, respectively. Average, superior, and inferior GC-IPL were correlated with AL (β=-2.056, P-value 0.000; β=-2.383, P-value 0.000; β=-1.721, P-value 0.000), but minimum GC-IPL was not (β=-1.056, P-value 0.115). None of the RNFL parameters were correlated with AL. This study establishes normative macular GC-IPL and RNFL thickness in children with refractive errors. Our results suggest that high definition optical coherence tomography RNFL parameters and minimum GC-IPL are not affected by AL or myopia in children, and therefore warrants further evaluation in pediatric glaucoma patients.

Localization of the androgen-synthesizing enzymes, androgen receptor, and sex steroids in the vagina: possible implications for the treatment of postmenopausal sexual dysfunction.

PubMed

Bertin, Jonathan; Dury, Alain Y; Ouellet, Johanne; Pelletier, Georges; Labrie, Fernand

2014-08-01

To better understand the mechanisms underlying the beneficial effects of the intravaginal administration of dehydroepiandrosterone (DHEA) observed in postmenopausal women on sexual dysfunction. To identify the distribution of the androgen-synthesizing enzymes as well as androgen receptor (AR) and measure steroid levels in the monkey vagina. The cynomolgus monkey (Macaca fascicularis), the closest model to the human, has been used to measure the expression levels of steroidogenic enzymes and androgen receptor by quantitative reverse transcription polymerase chain reaction (n=4), confirmed by immunohistochemistry, and immunofluorescence (n=3). DHEA and its androgenic metabolites were quantified by LC-MS/MS (n=4). The presence of SRD5A1, SRD5A2, HSD17B3, AR as well as nerve fibers (PGP 9.5) was investigated, and steroid levels were measured. AR is widely distributed within the vaginal epithelium and also in the lamina propria with a lower expression in the muscularis layer and blood vessel walls. Androgen-forming enzymes, on the other hand, are expressed in the vaginal stratified squamous epithelium at a relatively high level where they are uniformly distributed from the basal membrane up to the superficial keratinized cells. The enzymes are at a lower level in blood vessel walls and zona muscularis where nerve fibers are localized. DHEA and its androgen metabolites are present at biologically significant concentrations in the monkey vagina. The enzymes responsible for androgen formation as well as AR are at the highest level in the superficial layer of the stratified epithelium and muscularis layers of the vagina. These data provide a potential explanation for the described role of androgens in regulating vaginal lubrication, smooth muscle activity, blood flow, and the neuronal activity potentially involved in the correction of sexual dysfunction. © 2014 International Society for Sexual Medicine.

An ultrastructural study of calcitonin gene-related peptide-immunoreactive nerve fibers innervating the rat posterior longitudinal ligament. A morphologic basis for their possible efferent actions.

PubMed

Imai, S; Konttinen, Y T; Tokunaga, Y; Maeda, T; Hukuda, S; Santavirta, S

1997-09-01

The present study investigated ultrastructural characteristics of calcitonin gene-related peptide-immunoreactive nerve fibers in the posterior longitudinal ligament of the rat lumbar spine. To provide a morphologic basis for assessment of the afferent and, in particular, efferent functions of calcitonin gene-related peptide immunoreactive nerves in the posterior longitudinal ligament and their eventual role in degenerative spondylarthropathies and low back pain. Previous studies using light-microscopic localization of sensory neuronal markers such as calcitonin gene-related peptide have reported the presence of sensory fibers in the supporting structures of the vertebral column. Meanwhile, accumulating research data have suggested efferent properties for calcitonin gene-related peptide, i.e., a trophic action that alters the intrinsic properties of target cells not through transient action of synaptic transmission, but through long-lasting signal transmission by the secreted neuropeptides. To verify such trophic, paracrine actions of the calcitonin gene-related peptide-containing fibers in the posterior longitudinal ligament, however, ultrastructural details of the terminals and their spatial relationship to their eventual target structures have to be elucidated. Rat posterior longitudinal ligaments were stained immunohistochemically for calcitonin gene-related peptide. Light-microscopic analysis of the semithin sections facilitated subsequent electron microscopy of specific sites of the posterior longitudinal ligament to determine ultrastructural details and nerve fiber-target relationships. The rat lumbar posterior longitudinal ligament was found to be innervated by two distinctive calcitonin gene-related peptide immunoreactive nerve networks. In immunoelectronmicroscopy, the fibers of the deep network had numerous free nerve endings, whereas those of the superficial network showed spatial associations with other non-calcitonin gene-related peptide immunoreactive components of the network. In both systems, naked axons not covered by the Schwann cells made close spatial contact with smooth muscle cells: of blood vessels and resident posterior longitudinal ligament fibroblasts. The ultrastructural characteristics of the innervation of the rat posterior longitudinal ligament would be compatible not only with a nociceptive function, but also with neuromodulatory, vasoregulatory, and trophic functions, as has already been established in some visceral organs.

Estrogen replacement avoids the decrease of bladder innervations in ovariectomized adult virgin rats: in vivo stereological study.

PubMed

de Fraga, Rogerio; Palma, Paulo; Dambros, Miriam; Riccetto, Cassio L Z; Mandarim-de-Lacerda, Carlos; Miyaoka, Ricardo

2009-05-01

The authors quantified the nerve fibers in the bladder wall of ovariectomized rats with and without estradiol replacement. This study was conducted on 40 Wistar rats (3 months old). Group 1: remained intact; Group 2: underwent bilateral ovariectomy, and after 30 days was started on subcutaneous sesame oil replacement (0.2 ml per day) for 90 days; Group 3: sham-operated, and after 30 days was started on subcutaneous sesame oil replacement (0.2 ml per day) for 90 days; Group 4: bilateral ovariectomy, and after 30 days was started on subcutaneous injection of 17β-estradiol (10 μg/kg body weight) for 90 days. S-100 was used to stain nerves myelinized fibers on paraffin rat bladder sections. The G-50 grid system was used to quantitatively analyze the fibers. Long-term estrogen deprivation caused significant changes in bladder innervations, which can be characterized by a decreased number of nerve fibers by 65% (p < 0.001).

Potential Role of In Vivo Confocal Microscopy for Imaging Corneal Nerves in Transthyretin Familial Amyloid Polyneuropathy.

PubMed

Rousseau, Antoine; Cauquil, Cecile; Dupas, Benedicte; Labbé, Antoine; Baudouin, Christophe; Barreau, Emmanuel; Théaudin, Marie; Lacroix, Catherine; Guiochon-Mantel, Anne; Benmalek, Anouar; Labetoulle, Marc; Adams, David

2016-09-01

Small fiber neuropathy (SFN) is an important feature of transthyretin familial amyloid polyneuropathy (TTR-FAP). A practical and objective method for the clinical evaluation of SFN is needed to improve the management of this disease. In vivo confocal microscopy (IVCM) of the corneal nerves, a rapid noninvasive technique, may be used as a surrogate marker of SFN. To determine the correlation of SFN with IVCM in patients with TTR-FAP. A prospective, single-center, cross-sectional controlled study was conducted at the French National Reference Center for TTR-FAP from June 1, 2013, to June 30, 2014. Fifteen patients with TTR-FAP underwent a complete neurologic examination, including Neuropathy Impairment Score of the Lower Limbs, hand grip strength, and evaluation of vegetative dysfunction, as well as electrophysiologic studies (nerve conduction and electrochemical skin conductance) and intraepidermal nerve fiber density quantification. Patients and 15 controls (matched for age and sex) underwent ophthalmologic assessments, including corneal esthesiometry and IVCM. Correlation of corneal nerve fiber length (CNFL) with the severity of SFN. Of the 15 patients enrolled in the study, 6 were women (40%); mean (SD) age was 54.4 [13.7] years. The CNFL was shorter in the patients than in controls (13.08 vs 17.57 mm/mm2; difference of 4.49 [95% CI, 0.72 to 8.27]; P = .02). The patients' CNFL correlated with the severity of both autonomic neuropathy assessed by the Compound Autonomic Dysfunction Test (rs = 0.66 [95% CI, 0.22 to 0.87]; P = .008) or electrochemical skin conductance (rs = 0.80 [95% CI, 0.50 to 0.93]; P < .001) and sensorimotor neuropathy assessed using the Neuropathy Impairment Score of the Lower Limbs (rs = -0.58 [95% CI, -0.84 to -0.11]; P = .02). Patients with altered sensory nerve action potentials and intraepidermal nerve fiber density had a shorter CNFL (P = .04 and P = .02, respectively). The CNFL could be measured in all patients compared with sensory nerve action potentials (11 patients [73%; 95% CI, 44% to 92%]; P < .001) and intraepidermal nerve fiber density (4 patients [27%; 95% CI, 8% to 55%]; P < .001). In these 15 patients with TTR-FAP, IVCM measurement permitted rapid, noninvasive evaluation of small-fiber alterations in patients and could be used to assess SFN in this setting. The CNFL could be measured in all patients, thus avoiding the floor effect seen with other neuropathy measures. Longitudinal studies with more cases evaluated are needed to define the place of IVCM in monitoring patients with TTR-FAP.

Impacts of age and sex on retinal layer thicknesses measured by spectral domain optical coherence tomography with Spectralis.

PubMed

Nieves-Moreno, María; Martínez-de-la-Casa, José M; Morales-Fernández, Laura; Sánchez-Jean, Rubén; Sáenz-Francés, Federico; García-Feijoó, Julián

2018-01-01

To examine differences in individual retinal layer thicknesses measured by spectral domain optical coherence tomography (SD-OCT) (Spectralis®) produced with age and according to sex. Cross-sectional, observational study. The study was conducted in 297 eyes of 297 healthy subjects aged 18 to 87 years. In one randomly selected eye of each participant the volume and mean thicknesses of the different macular layers were measured by SD-OCT using the instrument's macular segmentation software. Volume and mean thickness of macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), retinal pigmentary epithelium (RPE) and photoreceptor layer (PR). Retinal thickness was reduced by 0.24 μm for every one year of age. Age adjusted linear regression analysis revealed mean GCL, IPL, ONL and PR thickness reductions and a mean OPL thickness increase with age. Women had significantly lower mean GCL, IPL, INL, ONL and PR thicknesses and volumes and a significantly greater mRNFL volume than men. The thickness of most retinal layers varies both with age and according to sex. Longitudinal studies are needed to determine the rate of layer thinning produced with age.

Construction of nerve guide conduits from cellulose/soy protein composite membranes combined with Schwann cells and pyrroloquinoline quinone for the repair of peripheral nerve defect

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luo, Lihua; Center of Molecular Medicine, School of Medicine, Hubei University of Arts and Sciences, Xiangyang 441053; Gan, Li

Regeneration and functional reconstruction of peripheral nerve defects remained a significant clinical challenge. Nerve guide conduits, with seed cells or neurotrophic factors (NTFs), had been widely used to improve the repair and regeneration of injured peripheral nerve. Pyrroloquinoline quinone (PQQ) was an antioxidant that can stimulate nerve growth factors (NGFs) synthesis and accelerate the Schwann cells (SCs) proliferation and growth. In present study, three kinds of nerve guide conduits were constructed: one from cellulose/SPI hollow tube (CSC), another from CSC combined with SCs (CSSC), and the third one from CSSC combined with PQQ (CSSPC), respectively. And then they were appliedmore » to bridge and repair the sciatic nerve defect in rats, using autograft as control. Effects of different nerve guide conduits on the nerve regeneration were comparatively evaluated by general analysis, sciatic function index (SFI) and histological analysis (HE and TEM). Newly-formed regenerative nerve fibers were observed and running through the transparent nerve guide conduits 12 weeks after surgery. SFI results indicated that the reconstruction of motor function in CSSPC group was better than that in CSSC and CSC groups. HE images from the cross-sections and longitudinal-sections of the harvested regenerative nerve indicated that regenerative nerve fibers had been formed and accompanied with new blood vessels and matrix materials in the conduits. TEM images also showed that lots of fresh myelinated and non-myelinated nerve fibers had been formed. Parts of vacuolar, swollen and abnormal axons occurred in CSC and CSSC groups, while the vacuolization and swell of axons was the least serious in CSSPC group. These results indicated that CSSPC group had the most ability to repair and reconstruct the nerve structure and functions due to the comprehensive contributions from hollow CSC tube, SCs and PQQ. As a result, the CSSPC may have the potential for the applications as nerve guide conduits in the field of nerve tissue engineering. - Highlights: • A novel nerve conduit was constructed and applied to repair nerve defect in rats. • Transparent hollow cellulose/soy protein isolate tube was used as conduit matrix. • Pyrroloquinoline quinine was adsorbed into the hollow tube as nerve growth factor. • Schwann cells were cultured into the hollow tube as seed cells. • The new nerve conduit could repair and reconstruct the peripheral nerve defects.« less

Morphological evidence for local microcircuits in rat vestibular maculae

NASA Technical Reports Server (NTRS)

Ross, M. D.

1997-01-01

Previous studies suggested that intramacular, unmyelinated segments of vestibular afferent nerve fibers and their large afferent endings (calyces) on type I hair cells branch. Many of the branches (processes) contain vesicles and are presynaptic to type II hair cells, other processes, intramacular nerve fibers, and calyces. This study used serial section transmission electron microscopy and three-dimensional reconstruction methods to document the origins and distributions of presynaptic processes of afferents in the medial part of the adult rat utricular macula. The ultrastructural research focused on presynaptic processes whose origin and termination could be observed in a single micrograph. Results showed that calyces had 1) vesiculated, spine-like processes that invaginated type I cells and 2) other, elongate processes that ended on type II cells pre- as well as postsynaptically. Intramacular, unmyelinated segments of afferent nerve fibers gave origin to branches that were presynaptic to type II cells, calyces, calyceal processes, and other nerve fibers in the macula. Synapses with type II cells occurred opposite subsynaptic cisternae (C synapses); all other synapses were asymmetric. Vesicles were pleomorphic but were differentially distributed according to process origin. Small, clear-centered vesicles, approximately 40-60 nm in diameter, predominated in processes originating from afferent nerve fibers and basal parts of calyces. Larger vesicles approximately 70-120 nm in diameter having approximately 40-80 nm electron-opaque cores were dominant in processes originating from the necks of calyces. Results are interpreted to indicate the existence of a complex system of intrinsic feedforward (postsynaptic)-feedback (presynaptic) connections in a network of direct and local microcircuits. The morphological findings support the concept that maculae dynamically preprocess linear acceleratory information before its transmission to the central nervous system.

Bradykinin activates a cross-signaling pathway between sensory and adrenergic nerve endings in the heart: a novel mechanism of ischemic norepinephrine release?

PubMed

Seyedi, N; Maruyama, R; Levi, R

1999-08-01

We had shown that bradykinin (BK) generated by cardiac sympathetic nerve endings (i.e., synaptosomes) promotes exocytotic norepinephrine (NE) release in an autocrine mode. Because the synaptosomal preparation may include sensory C-fiber endings, which BK is known to stimulate, sensory nerves could contribute to the proadrenergic effects of BK in the heart. We report that BK is a potent releaser of NE from guinea pig heart synaptosomes (EC(50) approximately 20 nM), an effect mediated by B(2) receptors, and almost completely abolished by prior C-fiber destruction or blockade of calcitonin gene-related peptide and neurokinin-1 receptors. C-fiber destruction also greatly decreased BK-induced NE release from the intact heart, whereas tyramine-induced NE release was unaffected. Furthermore, C-fiber stimulation with capsaicin and activation of calcitonin gene-related peptide and neurokinin-1 receptors initiated NE release from cardiac synaptosomes, indicating that stimulation of sensory neurons in turn activates sympathetic nerve terminals. Thus, BK is likely to release NE in the heart in part by first liberating calcitonin gene-related peptide and Substance P from sensory nerve endings; these neuropeptides then stimulate specific receptors on sympathetic terminals. This action of BK is positively modulated by cyclooxygenase products, attenuated by activation of histamine H(3) receptors, and potentiated at a lower pH. The NE-releasing action of BK is likely to be enhanced in myocardial ischemia, when protons accumulate, C fibers become activated, and the production of prostaglandins and BK increases. Because NE is a major arrhythmogenic agent, the activation of this interneuronal signaling system between sensory and adrenergic neurons may contribute to ischemic dysrhythmias and sudden cardiac death.

An immunoelectron microscopic study of methionine-enkephalin structures in cat prevertebral ganglia.

PubMed

Benfares, J; Henry, M; Cupo, A; Julé, Y

1995-03-01

Methionine-enkephalin-like immunoreactivity was detected in presynaptic nerve fibers and SIF cells in cat prevertebral ganglia. The immunoreactive nerve fibers contained a mixture of numerous small clear vesicles and a few large vesicles; the immunoreactivity was only confined to the large vesicles. Most of the immunoreactive fibers were in apposition with non-immunoreactive neuronal profiles, without any detectable synaptic membrane specializations. The other immunoreactive fibers formed synaptic contacts mainly with non-immunostained dendrites and to a lesser extent with axons and neuronal soma. The characterization at the ultrastructural level of the enkephalin-like immunoreactive structures is discussed as regards the modalities whereby opiates may be involved in sympathetic ganglionic transmission.

Salivation induced better lacrimal gland function in dry eyes.

PubMed

Pramanik, T; Ghising, R

2009-12-01

The dry eye syndrome is a common eye symptom causing blurry vision. To meet the demand of the modem world students and professionals are compelled to expose themselves to the computer screen for long stretch of time, which is one of the causes of dry eye. It is not always feasible to instil eyes with artificial tears time to time to protect them from dryness. Rather to adopt any simple physiological process associated with optimum lacrimation is a better option to keep eyes moist during computer works. Volunteers (n = 22) having mild dry eyes participated in this study. Tear production was assessed by Schirmer test by keeping Schirmer strip on ocular surface for 5 minutes and recording the length of the moistened area. Then the subject was allowed to keep a piece of lopsy candy (a sour fruit pulp mixed with sugar that is sweet and sour in taste) in mouth for 5 minutes that caused salivation. During salivation, again tear production was assessed. [It was standardized in such a way that, the length of the moistened strip will be 25 - 30 mm for normal eyes, 15 - 10 mm for dry eye, 06 - 10 mm for mild dry eye, 02 - 05 mm for moderate dryness and 00 - 01 mm for severe dry eye.] Tear production was found to be increased significantly (supported by increased length of moistened area of Schirmer strip) during salivation especially in dry eye in all volunteers. The lacrimal gland is the major contributor to the aqueous layer of the tear film which consists of water, electrolytes and proteins; secretion of which are under tight neural control. Anticholinergic agents play an important role in ocular dryness because of hypo-secretion. The sensory root of facial nucleus contains efferent preganglionic parasympathetic fibers for submandibular and sublingual salivary gland and lacrimal gland. The sensory root conveys gustatory fibers from the presulcul area (anterior two-third) of the tongue via the chorda tympani and via the palatine and greater petrosal nerve, taste fibers from the soft palate; it also carries preganglionic (secretomotor) innervations of the submandibular and sublingual salivary gland, lacrimal gland and gland of nasal and palatine mucosa. The taste sensation from the anterior two-third of the tongue, carried by the seventh cranial nerve, a nerve, parasympathetic in nature that contains efferent preganglionic fibers to lacrimal gland. Being stimulated, seventh cranial nerve helps in secretion of tear from the lacrimal glands and gives a sense of relief to the persons facing the problem of mild dryness of eyes.

Chronic migraine is associated with reduced corneal nerve fiber density and symptoms of dry eye.

PubMed

Kinard, Krista I; Smith, A Gordon; Singleton, J Robinson; Lessard, Margaret K; Katz, Bradley J; Warner, Judith E A; Crum, Alison V; Mifflin, Mark D; Brennan, Kevin C; Digre, Kathleen B

2015-04-01

We used in vivo corneal confocal microscopy to investigate structural differences in the sub-basal corneal nerve plexus in chronic migraine patients and a normal population. We used a validated questionnaire and tests of lacrimal function to determine the prevalence of dry eye in the same group of chronic migraine patients. Activation of the trigeminal system is involved in migraine. Corneal nociceptive sensation is mediated by trigeminal axons that synapse in the gasserian ganglion and the brainstem, and serve nociceptive, protective, and trophic functions. Noninvasive imaging of the corneal sub-basal nerve plexus is possible with in vivo corneal confocal microscopy. For this case-control study, we recruited chronic migraine patients and compared them with a sex- and age-similar group of control subjects. Patients with peripheral neuropathy, a disease known to be associated with a peripheral neuropathy, or prior corneal or intraocular surgery were excluded. Participants underwent in vivo corneal confocal microscopy using a Heidelberg Retinal Tomography III confocal microscope with a Rostock Cornea Module. Nerve fiber length, nerve branch density, nerve fiber density, and tortuosity coefficient were measured using established methodologies. Migraine participants underwent testing of basal tear production with proparacaine, corneal sensitivity assessment with a cotton-tip applicator, measurement of tear break-up time, and completion of a validated dry eye questionnaire. A total of 19 chronic migraine patients and 30 control participants completed the study. There were no significant differences in age or sex. Nerve fiber density was significantly lower in migraine patients compared with controls (48.4 ± 23.5 vs. 71.0 ± 15.0 fibers/mm2 , P < .001). Nerve fiber length was decreased in the chronic migraine group compared with the control group, but this difference was not statistically significant (21.5 ± 11.8 vs. 26.8 ± 5.9 mm/mm2, P < .084). Nerve branch density was similar in the two groups (114.0 ± 92.4 vs. 118.1 ± 55.9 branches/mm2 , P < .864). Tortuosity coefficient and log tortuosity coefficient also were similar in the chronic migraine and control groups. All migraine subjects had symptoms consistent with a diagnosis of dry eye syndrome. We found that in the sample used in this study, the presence of structural changes in nociceptive corneal axons lends further support to the hypothesis that the trigeminal system plays a critical role in the pathogenesis of migraine. In vivo corneal confocal microscopy holds promise as a biomarker for future migraine research as well as for studies examining alterations of corneal innervation. Dry eye symptoms appear to be extremely prevalent in this population. The interrelationships between migraine, corneal nerve architecture, and dry eye will be the subject of future investigations. © 2015 American Headache Society.

Multilayered thermal insulation formed of zirconia bonded layers of zirconia fibers and metal oxide fibers and method for making same

DOEpatents

Wrenn, Jr., George E.; Holcombe, Jr., Cressie E.

1988-01-01

A multilayered thermal insulating composite is formed of a first layer of zirconia-bonded zirconia fibers for utilization near the hot phase or surface of a furnace or the like. A second layer of zirconia-bonded metal oxide fibers is attached to the zirconia fiber layer by a transition layer formed of intermingled zirconia fibers and metal oxide fibers. The thermal insulation is fabricated by vacuum molding with the layers being sequentially applied from aqueous solutions containing the fibers to a configured mandrel. A portion of the solution containing the fibers forming the first layer is intermixed with the solution containing the fibers of the second layer for forming the layer of mixed fibers. The two layers of fibers joined together by the transition layer are saturated with a solution of zirconium oxynitrate which provides a zirconia matrix for the composite when the fibers are sintered together at their nexi.

Multilayered thermal insulation formed of zirconia bonded layers of zirconia fibers and metal oxide fibers and method for making same

DOEpatents

Wrenn, G.E. Jr.; Holcombe, C.E. Jr.

1988-09-13

A multilayered thermal insulating composite is formed of a first layer of zirconia-bonded zirconia fibers for utilization near the hot phase or surface of a furnace or the like. A second layer of zirconia-bonded metal oxide fibers is attached to the zirconia fiber layer by a transition layer formed of intermingled zirconia fibers and metal oxide fibers. The thermal insulation is fabricated by vacuum molding with the layers being sequentially applied from aqueous solutions containing the fibers to a configured mandrel. A portion of the solution containing the fibers forming the first layer is intermixed with the solution containing the fibers of the second layer for forming the layer of mixed fibers. The two layers of fibers joined together by the transition layer are saturated with a solution of zirconium oxynitrate which provides a zirconia matrix for the composite when the fibers are sintered together at their nexi.

Ganglion cell-inner plexiform layer and retinal nerve fiber layer thickness according to myopia and optic disc area: a quantitative and three-dimensional analysis.

PubMed

Seo, Sam; Lee, Chong Eun; Jeong, Jae Hoon; Park, Ki Ho; Kim, Dong Myung; Jeoung, Jin Wook

2017-03-11

To determine the influences of myopia and optic disc size on ganglion cell-inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (RNFL) thickness profiles obtained by spectral domain optical coherence tomography (OCT). One hundred and sixty-eight eyes of 168 young myopic subjects were recruited and assigned to one of three groups according to their spherical equivalent (SE) values and optic disc area. All underwent Cirrus HD-OCT imaging. The influences of myopia and optic disc size on the GCIPL and RNFL thickness profiles were evaluated by multiple comparisons and linear regression analysis. Three-dimensional surface plots of GCIPL and RNFL thickness corresponding to different combinations of myopia and optic disc size were constructed. Each of the quadrant RNFL thicknesses and their overall average were significantly thinner in high myopia compared to low myopia, except for the temporal quadrant (all Ps ≤0.003). The average and all-sectors GCIPL were significantly thinner in high myopia than in moderate- and/or low-myopia (all Ps ≤0.002). The average OCT RNFL thickness was correlated significantly with SE (0.81 μm/diopter, P < 0.001), axial length (-1.44 μm/mm, P < 0.001), and optic disc area (5.35 μm/mm 2 , P < 0.001) by linear regression analysis. As for the OCT GCIPL parameters, average GCIPL thickness showed a significant correlation with SE (0.84 μm/diopter, P < 0.001) and axial length (-1.65 μm/mm, P < 0.001). There was no significant correlation of average GCIPL thickness with optic disc area. Three-dimensional curves showed that larger optic discs were associated with increased average RNFL thickness and that more-myopic eyes were associated with decreased average GCIPL and RNFL thickness. Myopia can significantly affect GCIPL and RNFL thickness profiles, and optic disc size has a significant influence on RNFL thickness. The current OCT maps employed in the evaluation of glaucoma should be analyzed in consideration of refractive status and optic disc size.