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Sample records for acute central retinal

  1. Visual prognosis following treatment of acute central retinal artery obstruction.

    PubMed Central

    Augsburger, J J; Magargal, L E

    1980-01-01

    The authors report the visual outcome in 34 consecutive cases of treated acute central retinal artery obstruction. Visual acuity equal to or better than 6/30 was recovered in 35% of the cases. The presenting visual acuity and duration of visual impairment appear to correlate with visual prognosis. PMID:7448144

  2. Management of acute central retinal artery occlusion: Intravenous thrombolysis is feasible and safe.

    PubMed

    Préterre, Cécile; Godeneche, Gaelle; Vandamme, Xavier; Ronzière, Thomas; Lamy, Matthias; Breuilly, Christophe; Urbanczyk, Cédric; Wolff, Valérie; Lebranchu, Pierre; Sevin-Allouet, Mathieu; Guillon, Benoit

    2017-01-01

    Background Although acute central retinal artery occlusion is as a stroke in the carotid territory (retinal artery), its management remains controversial. The aim of this study was to assess the feasibility and safety of intravenous thrombolysis delivered within 6 h of central retinal artery occlusion in French stroke units. Methods We performed a retrospective analysis of patients treated with intravenous alteplase (recombinant tissue-plasminogen activator), based on stroke units thrombolysis registers from June 2005 to June 2015, and we selected those who had acute central retinal artery occlusion. The feasibility was assessed by the ratio of patients that had received intravenous alteplase within 6 h after central retinal artery occlusion onset among those who had been admitted to the same hospital for acute central retinal artery occlusion. All adverse events were documented. Results Thirty patients were included. Visual acuity before treatment was limited to "hand motion", or worse, in 90% of the cases. The mean onset-to-needle time was 273 min. The individuals treated with intravenous alteplase for central retinal artery occlusion represented 10.2% of all of the patients hospitalized for central retinal artery occlusion in 2013 and 2014. We observed one occurrence of major bleeding, a symptomatic intracerebral hemorrhage. Conclusion When applied early on, intravenous thrombolysis appears to be feasible and safe, provided that contraindications are given due consideration. Whether intravenous thrombolysis is more effective than conservative therapy remains to be determined. In order to conduct a well-designed prospective randomized control trial, an organized network should be in place.

  3. Assessment of ischemia in acute central retinal vein occlusion from inner retinal reflectivity on spectral domain optical coherence tomography

    PubMed Central

    Browning, David J; Punjabi, Omar S; Lee, Chong

    2017-01-01

    Purpose To determine the relationship between different spectral domain optical coherence tomography (SD-OCT) signs of retinal ischemia in acute central retinal vein occlusion (CRVO) and whether they predict anterior segment neovascularization (ASNV). Design Retrospective, observational study. Subjects Thirty-nine consecutive patients with acute CRVO and 12 months of follow-up. Methods We graded baseline SD-OCTs for increased reflectivity of the inner retina, loss of definition of inner retinal layers, presence of a prominent middle-limiting membrane (p-MLM) sign, and presence of paracentral acute middle maculopathy (PAMM). Graders were masked with respect to all clinical information. Results The intraclass correlation coefficients (ICCs) of grading–regrading by graders 1 and 2 were 0.8104, 95% confidence interval (CI) (0.6686, 0.8956), and 0.7986, 95% CI (0.6475, 0.8892), respectively. The intragrader coefficients of repeatability (COR) for graders 1 and 2 were 0.94 and 0.92, respectively. The ICC of graders 1 compared with 2 was 0.8039, 95% CI (0.6544, 0.8916). The intergrader COR was 0.80. SD-OCT grades of baseline ischemia were not associated with baseline visual acuity (VA), central subfield mean thickness (CSMT), or relative afferent pupillary defect; 12-month VA, CSMT, change in VA, change in CSMT, number of antivascular endothelial growth factor injections or corticosteroid injections, or proportion of eyes developing ASNV. SD-OCT grades of ischemia did not correlate with the proportion of eyes having the p-MLM sign or PAMM. PAMM and p-MLM are milder signs of ischemia than increased reflectivity of the inner retinal layers. Eyes with PAMM can evolve, losing PAMM and gaining the p-MLM sign. Conclusion Grading of ischemia from SD-OCT in acute CRVO was repeatable within graders and reproducible across graders for the graders in this study. SD-OCT signs of ischemia are not correlated with each other and do not reliably predict subsequent ASNV. Close

  4. Optical coherence tomography angiography in paracentral acute middle maculopathy secondary to central retinal vein occlusion.

    PubMed

    Casalino, G; Williams, M; McAvoy, C; Bandello, F; Chakravarthy, U

    2016-06-01

    PurposeTo report the clinical course and the optical coherence tomography angiography (OCTA) findings of patients presenting with paracentral acute middle maculopathy (PAMM) and central retinal vein occlusion (CRVO).MethodsRetrospective case series. Clincal records and multimodal imaging findings of patients presenting with PAMM and CRVO were reviewed.ResultsThree eyes of three patients (2 males; mean age: 66 years) were included in the study. Mean follow-up was 9 months and images using OCTA (AngioVue OCT angiography system, Optovue, Inc., Fremont, CA, USA) were available at the last follow-up visit. During follow-up, best corrected visual acuity (BCVA) of case 1 was unchanged at 85 ETDRS letters and OCTA revealed a mild attenuation of the perifoveal deep capillary plexus (DCP); in case 2, BCVA changed from 83 to 77 ETDRS letters and OCTA revealed patchy areas of attenuation and pruning of the DCP; in case 3, BCVA decreased from 26 to 8 ETDRS letters and OCTA revealed extensive areas of DCP dropout.ConclusionThe natural course of visual acuity in patients with PAMM secondary to CRVO may vary. In these patients, the extent of DCP dropout on OCTA may reflect the extent of visual acuity impairment.

  5. Therapy for acute retinal necrosis.

    PubMed

    Kawaguchi, Tatsushi; Spencer, Doran B; Mochizuki, Manabu

    2008-01-01

    Acute retinal necrosis is a progressive necrotizing retinopathy caused by herpes simplex virus (HSV) or varicella zoster virus (VZV). The mainstay of its treatment is antiviral therapy against these pathogenic organisms, such as intravenous acyclovir or oral valacyclovir. Systemic and topical corticosteroids together with antiviral therapy are used as an anti-inflammatory treatment to minimize damages to the optic nerve and retinal blood vessels. Because the majority of severe cases of the disease show occlusive retinal vasculitis, a low dosage of aspirin is used as anti-thrombotic treatment. Vitreo-retinal surgery is useful to repair rhegmatogenous retinal detachment, one of the main late-stage complications. Moreover, recent articles have reported some encouraging results of prophylactic vitrectomy before rhegmatogenous retinal detachment occurs. The efficacy of laser photocoagulation to prevent the development or extension of rhegmatogenous retinal detachment is controversial. Despite these treatments, the visual prognosis of acute retinal necrosis is still poor, in particular VZV-induced acute retinal necrosis.

  6. ACUTE RETINAL ARTERIAL OCCLUSIVE DISORDERS

    PubMed Central

    Hayreh, Sohan Singh

    2011-01-01

    The initial section deals with basic sciences; among the various topics briefly discussed are the anatomical features of ophthalmic, central retinal and cilioretinal arteries which may play a role in acute retinal arterial ischemic disorders. Crucial information required in the management of central retinal artery occlusion (CRAO) is the length of time the retina can survive following that. An experimental study shows that CRAO for 97 minutes produces no detectable permanent retinal damage but there is a progressive ischemic damage thereafter, and by 4 hours the retina has suffered irreversible damage. In the clinical section, I discuss at length various controversies on acute retinal arterial ischemic disorders. Classification of acute retinal arterial ischemic disorders These are of 4 types: CRAO, branch retinal artery occlusion (BRAO), cotton wools spots and amaurosis fugax. Both CRAO and BRAO further comprise multiple clinical entities. Contrary to the universal belief, pathogenetically, clinically and for management, CRAO is not one clinical entity but 4 distinct clinical entities – non-arteritic CRAO, non-arteritic CRAO with cilioretinal artery sparing, arteritic CRAO associated with giant cell arteritis (GCA) and transient non-arteritic CRAO. Similarly, BRAO comprises permanent BRAO, transient BRAO and cilioretinal artery occlusion (CLRAO), and the latter further consists of 3 distinct clinical entities - non-arteritic CLRAO alone, non-arteritic CLRAO associated with central retinal vein occlusion and arteritic CLRAO associated with GCA. Understanding these classifications is essential to comprehend fully various aspects of these disorders. Central retinal artery occlusion The pathogeneses, clinical features and management of the various types of CRAO are discussed in detail. Contrary to the prevalent belief, spontaneous improvement in both visual acuity and visual fields does occur, mainly during the first 7 days. The incidence of spontaneous visual

  7. Cilio-retinal arterial circulation in central retinal vein occlusion.

    PubMed Central

    McLeod, D

    1975-01-01

    The hypothesis that an occlusion of the central retinal artery is an essential prerequisite for haemorrhage formation after central retinal vein obstruction has been investigated by examining the fundus changes in patients with a cilio-retinal arterial circulation; the findings are at variance with the 'combined occlusion hypothesis'. Comparisons were made between the pathological features in two retinal capillary beds with independent sources of arterial supply--namely, the central retinal and cilio-retinal arteries--but with an obstructed venous drainage channel common to both--namely, the central retinal vein. The importance of intraluminal pressure changes (as distinct from perfusion changes) in the causation of haemorrhages and oedema after venous occlusion is stressed, and the role of arterial disease in the pathogenesis of venous occlusions is distinguished from its role in determining the sequelae of such occlusions. Images PMID:1203235

  8. Hemi-central retinal artery occlusion in young adults.

    PubMed

    Rishi, Pukhraj; Rishi, Ekta; Sharma, Tarun; Mahajan, Sheshadri

    2010-01-01

    Amongst the clinical presentations of retinal artery occlusion, hemi-central retinal artery occlusion (Hemi-CRAO) is rarely described. This case series of four adults aged between 22 and 36 years attempts to describe the clinical profile, etiology and management of Hemi-CRAO. Case 1 had an artificial mitral valve implant. Polycythemia and malignant hypertension were noted in Case 2. The third patient had Leiden mutation while the fourth patient had Eisenmenger's syndrome. Clinical examination and fundus fluorescein angiography revealed a bifurcated central retinal artery at emergence from the optic nerve head, in all cases. Color Doppler examination of the central retinal artery confirmed branching of the artery behind the lamina cribrosa. It is hypothesized that bifurcation of central retinal artery behind the lamina cribrosa may predispose these hemi-trunks to develop an acute occlusion if associated with underlying risk factors. The prognosis depends upon arterial recanalisation and etiology of the thromboembolic event.

  9. Central retinal artery occlusion (reversible in sickle trait with glaucoma.

    PubMed Central

    Radius, R L; Finkelstein, D

    1976-01-01

    We report a case of central retinal artery occlusion in an 18-year-old black woman with sickle-trait haemoglobinopathy and acute glaucoma after hyphaema. The central retinal artery occlusion occurred immediately after treatment of the glaucoma with osmotic agents, raising the possibility that they played a precipitating role. We suggest that osmotic agents be used with extreme caution in sickle patients with glaucoma. The occlusion was treated by anterior chamber paracentesis with eventual return of good vision. The reversibility of retinal and optic nerve function after total ischaemia is discussed. PMID:952815

  10. Retinal fractals and acute lacunar stroke.

    PubMed

    Cheung, Ning; Liew, Gerald; Lindley, Richard I; Liu, Erica Y; Wang, Jie Jin; Hand, Peter; Baker, Michelle; Mitchell, Paul; Wong, Tien Y

    2010-07-01

    This study aimed to determine whether retinal fractal dimension, a quantitative measure of microvascular branching complexity and density, is associated with lacunar stroke. A total of 392 patients presenting with acute ischemic stroke had retinal fractal dimension measured from digital photographs, and lacunar infarct ascertained from brain imaging. After adjusting for age, gender, and vascular risk factors, higher retinal fractal dimension (highest vs lowest quartile and per standard deviation increase) was independently and positively associated with lacunar stroke (odds ratio [OR], 4.27; 95% confidence interval [CI], 1.49-12.17 and OR, 1.85; 95% CI, 1.20-2.84, respectively). Increased retinal microvascular complexity and density is associated with lacunar stroke.

  11. Leuprolide acetate and central retinal vein occlusion.

    PubMed

    Federici, Thomas J

    2007-01-01

    A 63-year-old man suffered a central retinal vein occlusion 2 months after he began taking leuprolide acetate for prostate cancer. Despite control for possible systemic hypertension (126/90 mm Hg) and mild hypercholesterolemia (total cholesterol level =246 mg/dL [range: 16 to 200 mg/dL], high-density lipoprotein level =67 mg/dL [range: 40 to 59 mg/dL], and low-density lipoprotein level =144 mg/dL [range: 0 to 130 mg/dL]), progression of the venous occlusive disease occurred. Leuprolide acetate, which is associated with thromboembolic events and diffuse intravascular coagulation, may be implicated in central retinal vein occlusion.

  12. Combined occlusion of the central retinal artery and central retinal vein following blunt ocular trauma: a case report.

    PubMed Central

    Noble, M J; Alvarez, E V

    1987-01-01

    A healthy young woman suffered complete loss of the vision of one eye following a blunt ocular injury. She sustained a combined occlusion of the central retinal artery and central retinal vein of the affected eye. Initially few retinal haemorrhages were present, but they increased considerably in number and size during the day following injury. Images PMID:3689734

  13. Quantification of retinal layer thickness changes in acute macular neuroretinopathy

    PubMed Central

    Munk, Marion R; Beck, Marco; Kolb, Simone; Larsen, Michael; Hamann, Steffen; Valmaggia, Christophe; Zinkernagel, Martin S

    2017-01-01

    Purpose To quantitatively evaluate retinal layer thickness changes in acute macular neuroretinopathy (AMN). Methods AMN areas were identified using near-infrared reflectance (NIR) images. Intraretinal layer segmentation using Heidelberg software was performed. The inbuilt ETDRS -grid was moved onto the AMN lesion and the mean retinal layer thicknesses of the central grid were recorded and compared with the corresponding area of the fellow eye at initial presentation and during follow-up. Results Eleven patients were included (mean age 26±6 years). AMN lesions at baseline had a significantly thinner outer nuclear layer (ONL) (51±21 µm vs 73±17 µm, p=0.002). The other layers, including inner nuclear layer (37±8 µm vs 38±6 µm, p=0.9) and outer plexiform layer (OPL) (45±19 µm vs 33±16 µm, p=0.1) did not show significant differences between the study eyes and fellow eyes. Adjacent to NIR image lesions, areas of OPL thickening were identified (study eye: 50±14 µm vs fellow eye: 39±16 µm, p=0.005) with corresponding thinning of ONL (study eye: 52±16 µm vs fellow eye: 69±16 µm, p=0.002). Conclusions AMN presents with characteristic quantitative retinal changes and the extent of the lesion may be more extensive than initially presumed from NIR image lesions. PMID:27170518

  14. Central Retinal Vein Occlusion Associated With Severe Vitamin D Deficiency.

    PubMed

    Talcott, Katherine E; Eliott, Dean

    2016-04-01

    Central retinal vein occlusion (CRVO) is thought to occur due to thrombotic occlusion of the central retinal vein at or just posterior to the lamina cribrosa. Studies have shown that the incidence of CRVO may be higher in winter to early spring, suggesting that low vitamin D levels may play a role; however, no studies have measured vitamin D levels in patients with CRVO. In addition, there is mounting evidence that patients with vitamin D deficiency may be predisposed to thrombotic events. The authors report a case of central retinal vein occlusion associated with marked vitamin D deficiency.

  15. Neurophysiology of central retinal degeneration in cat.

    PubMed

    Levick, W R; Thibos, L N

    1993-01-01

    Receptive fields of ganglion cells have been studied in cats possessing a chronic, arrested lesion of central retinal degeneration. Lesions were characterized by an ophthalmoscopically sharp border separating apparently normal retina from the region of the lesion. Under direct ophthalmoscopic guidance, a succession of recordings was obtained from ganglion cells having cell bodies at various positions relative to the lesion. Cells located more than 1 deg outside the ophthalmoscopic border had normal visual sensitivity as assessed by area-threshold experiments. Inside the lesion cells within 1 deg of the border had reduced sensitivity which often precluded functional classification by the usual visual tests. Ganglion cells located more than 1 deg inside the border of large lesions were blind and some had abnormal patterns of maintained discharge of action potentials. Nevertheless, the antidromic latencies of these blind cells fell into the familiar conduction groups (T1/T2/T3). Receptive-field maps of cells near the border of the lesion often appeared truncated, with the missing portion of the field covered by the lesion. These observations were consistent with the abnormal form of area-threshold curves. Although the responsiveness of cells near the lesion was abnormally low for grating stimuli, cutoff spatial frequency and orientation bias of these cells were within normal limits.

  16. [Acute bilateral impaired vision with central scotoma in an 11-year-old boy].

    PubMed

    Pollithy, S; Ach, T; Schaal, K B; Dithmar, S

    2012-09-01

    This article presents a case of acute bilateral impaired vision and central scotoma in an 11-year-old boy. Looking directly into a laser beam of a laser pointer for only a few seconds can cause retinal damage in the form of lesions of the retinal pigment epithelium and the photoreceptor layer, up to retinal hemorrhage. Patients often complain about impaired vision and a central scotoma of the affected eye.

  17. SURGICAL EMBOLECTOMY FOR FOVEA-THREATENING ACUTE RETINAL ARTERY OCCLUSION

    PubMed Central

    Almeida, David R.P.; Mammo, Zaid; Chin, Eric K.

    2016-01-01

    Purpose: To describe a technique of surgical intraocular embolectomy in patients with acute fovea-threatening branch retinal artery occlusion. Methods: Pars plana vitrectomy with embolectomy involving embolus isolation, dissection, and removal in patients with an acute fovea-threatening arterial occlusion without a patent cilioretinal artery. Results: The surgical technique involves a core vitrectomy. The blocked artery is incised using a microvitreoretinal blade, and microsurgical forceps are used to retrieve the embolus. No significant complications were noted. The study technique offers an excellent safety profile and minimizes the risk of vitreous hemorrhage by carefully dissecting the vascular adventitial sheath and isolating the embolus. Conclusion: Surgical embolectomy is a viable technique for patients with acute fovea-threatening arterial occlusions without patent cilioretinal artery. Careful dissection and retrieval of the embolus minimizes the risk of vitreous hemorrhage, which is an important improvement in previous techniques for management of acute retinal arterial occlusions. PMID:26674278

  18. Acute necrotizing retinal vasculitis as onset of systemic lupus erythematosus

    PubMed Central

    Monov, Simeon; Hristova, Ruska; Dacheva, Rositza; Toncheva, Reni; Shumnalieva, Russka; Shoumnalieva-Ivanova, Viara; Monova, Daniela

    2017-01-01

    Abstract Rationale: Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by autoantibody production, complement activation, and deposition of immune complexes in tissues and organs. SLE can involve any region of the visual system. Although ocular manifestations are not part of the classification criteria for SLE, they can be observed in up to one-third of the patients with SLE. They are rarely reported at the time of disease onset. Retinal vasculitis is usually associated with active generalized disease. Due to its low frequency, we report a case of acute necrotizing retinal vasculitis as onset of SLE. Patient concerns and diagnosis: A 25-year-old white female was referred to the rheumatology clinic with gradually and rapid deterioration of the vision due to abnormal vessel permeability in the right fundus with edema along the vessels, occlusion of arterial branches in the middle periphery with leakage of the dye in these areas and indentical but less prominent changes with cotton wool spots in the papillomacular area and extensive hemorrhages in the left eye. The onset of malar rash, arthralgias and positive antinuclear, anti-double stranded DNA, anti-ribosomal P and anti-β2 glycoprotein I antibodies with decreased C4 complement levels, as well as the positive lupus-band test confirmed the diagnosis of SLE. Interventions: Aggressive immunomodulating therapy with high-dose methylprednisolone, intravenous immunoglobulin, and cyclophosphamide was used for suppression of the disease activity followed by azathioprine as maintaince therapy. Outcomes: Substantial improvement and partial resorption of the vasculitic changes, including central retinal artery and vein, was achieved prominently in the left eye. The study was conducted in accordance with the Declaration of Helsinki and written informed consent was obtained from the patient. Because of this, there is no need to conduct special ethic review and the ethical approval is not necessary

  19. Clinical Manifestation of Self-Limiting Acute Retinal Necrosis

    PubMed Central

    Brydak-Godowska, Joanna; Borkowski, Piotr; Szczepanik, Szymon; Moneta-Wielgoś, Joanna; Kęcik, Dariusz

    2014-01-01

    Background The purpose of this paper was to present a case series of self-limiting, peripheral acute retinal necrosis and to demonstrate efficacy of treatment with valacyclovir in patients resistant to acyclovir. The diagnosis was made on ophthalmoscopic examination and positive serum tests for herpes viruses. Material/Methods Ten patients (6F and 4M) aged 19–55 years were diagnosed and treated for self-limiting acute retinal necrosis (ARN). The following endpoints were reported: visual outcomes, clinical features, disease progression, treatment, and complications. Patients received only symptomatic treatment because they did not consent to vitreous puncture. Results Peripheral, mild retinitis was diagnosed in all eyes at baseline. Initially, all patients were treated with systemic acyclovir (800 mg, 5 times a day), prednisone (typically 40–60 mg/day), and aspirin in an outpatient setting. In 6 patients, treatment was discontinued at 6 months due to complete resolution of the inflammatory process. Four patients with immune deficiency showed signs and symptoms of chronic inflammation. Two patients did not respond to acyclovir (2 non-responders); however, those patients were successfully treated with valacyclovir. Complete resolution of inflammatory lesions was observed in 8 patients. In 2 patients, the disease progressed despite treatment – 1 female patient after kidney transplant who stopped the prescribed medications, and 1 male patient with SLE and antiphospholipid syndrome who experienced breakthrough symptoms on-treatment. He died due to cerebral venous sinus thrombosis. Neurological complications (encephalitis and meningitis) were observed in 2 female patients. Prophylactic laser photocoagulation was performed in 1 subject. Conclusions A series of cases of self-limiting acute retinal necrosis (ARN) is presented. This clinical form of ARN can resemble toxoplasmic retinitis in some cases. Oral antiviral medications provide an effective alternative to

  20. RI in central retinal artery as assessed by CDI does not correspond to retinal vascular resistance.

    PubMed

    Polska, E; Kircher, K; Ehrlich, P; Vecsei, P V; Schmetterer, L

    2001-04-01

    The aim of the present study was to investigate the association between ultrasound Doppler measurements of resistive index (RI) in the central retinal artery and retinal vascular resistance (R) assessed with laser Doppler velocimetry, vessel size measurement, and calculation of ocular perfusion pressure (PP) in healthy subjects. An increase in vascular resistance was induced by inhalation of 100% O(2). During hyperoxia no significant changes in PP were observed. Mean flow velocity in main retinal veins was reduced by -27.5 +/- 2.0%. The average decrease in diameter was -11.5 +/- 1.0%. R, which was calculated as the ratio of PP to flow rate, increased by 97.6 +/- 7.7%. RI increased as well, but the effect was much smaller (6.6 +/- 2.2%). In addition, a negative correlation was found between baseline values of R and RI (r = -0.83). During hyperoxia R and RI were not associated. In conclusion, our data indicate that RI as assessed with color Doppler imaging in the central retinal artery is not an adequate measure of R.

  1. Anti-VEGF treatment and peripheral retinal nonperfusion in patients with central retinal vein occlusion

    PubMed Central

    Abri Aghdam, Kaveh; Reznicek, Lukas; Soltan Sanjari, Mostafa; Klingenstein, Annemarie; Kernt, Marcus; Seidensticker, Florian

    2017-01-01

    Purpose To evaluate the association between the size of peripheral retinal nonperfusion and the number of intravitreal ranibizumab injections in patients with treatment-naïve central retinal vein occlusion (CRVO). Methods Fifty-four patients with treatment-naïve CRVO and macular edema were included. Each patient underwent a full ophthalmologic examination including optical coherence tomography imaging and ultrawide-field fluorescein angiography. Monthly intravitreal ranibizumab injections were applied according to the recommendations of the German Ophthalmologic Society. Two ophthalmologists quantified the areas of peripheral retinal nonperfusion (group 1= less than five disc areas, group 2= more than five disc areas). Correlation analyses between the size of nonperfusion with best-corrected visual acuity, central subfield thickness, and the number of intravitreal injections were performed. Results Best-corrected visual acuity improved significantly after intravitreal injections (P<0.001, both groups). Final central subfield thickness after treatment did not significantly differ between both groups (P=0.92, P=0.96, respectively). Mean number of injections in group 1 and group 2 was 4.12±2.73 and 9.32±3.84, respectively (P<0.001). There was a significant positive correlation between areas of nonperfusion and the number of injections in each group. (R=0.97, P<0.001; R=0.94, P<0.001, respectively). Conclusion Peripheral retinal nonperfusion in patients with CRVO correlates significantly with the number of needed intravitreal ranibizumab injections. Ultrawide-field fluorescein angiography is a useful tool for detection of peripheral retinal ischemia, which may have direct implications in the diagnosis, follow-up, and treatment of these patients. PMID:28243056

  2. Diverse Central Projection Patterns of Retinal Ganglion Cells.

    PubMed

    Martersteck, Emily M; Hirokawa, Karla E; Evarts, Mariah; Bernard, Amy; Duan, Xin; Li, Yang; Ng, Lydia; Oh, Seung W; Ouellette, Benjamin; Royall, Joshua J; Stoecklin, Michelle; Wang, Quanxin; Zeng, Hongkui; Sanes, Joshua R; Harris, Julie A

    2017-02-21

    Understanding how >30 types of retinal ganglion cells (RGCs) in the mouse retina each contribute to visual processing in the brain will require more tools that label and manipulate specific RGCs. We screened and analyzed retinal expression of Cre recombinase using 88 transgenic driver lines. In many lines, Cre was expressed in multiple RGC types and retinal cell classes, but several exhibited more selective expression. We comprehensively mapped central projections from RGCs labeled in 26 Cre lines using viral tracers, high-throughput imaging, and a data processing pipeline. We identified over 50 retinorecipient regions and present a quantitative retina-to-brain connectivity map, enabling comparisons of target-specificity across lines. Projections to two major central targets were notably correlated: RGCs projecting to the outer shell or core regions of the lateral geniculate projected to superficial or deep layers within the superior colliculus, respectively. Retinal images and projection data are available online at http://connectivity.brain-map.org.

  3. Acute occlusion of the retinal arteries: current concepts and recent advances in diagnosis and management

    PubMed Central

    Beatty, S; Eong, K

    2000-01-01

    Purpose/Background—Central retinal artery occlusion (CRAO) is usually a blinding event, and is not an infrequent presentation to the accident and emergency (A&E) department. The evidence-base in support of current treatment options is weak. Methods—This paper reviewed the literature germane to the diagnostic, therapeutic and prognostic aspects of retinal arterial occlusive disease. Results—The visual prognosis associated with CRAO remains poor, and current therapeutic practices are of unproven benefit. The non-ophthalmologist in the A&E department should lie the patient flat and give a stat dose of intravenous acetazolamide in an attempt to improve the retinal perfusion pressure. Conclusion—The management of acute occlusion of the central retinal artery has not changed over the past 30 years, although the potential benefits of superselective intra-arterial fibrinolytic therapy warrant evaluation in a randomised controlled trial. The identification of underlying pathology is an essential component of medical care, and all cases should be followed up by an ophthalmologist because of the possibility of ocular rubeosis. PMID:11005400

  4. Spontaneous central retinal artery occlusion in a teenager with sickle cell trait.

    PubMed

    Pai, Sivakami A; Hebri, Sudhira Pai; Dekhain, Moza A

    2015-01-01

    Sickle cell trait (SCT) is traditionally considered a benign condition by ophthalmologists. Several studies have reported ocular complications in SCT, but these complications have been described as a consequence of trauma, exertion, and associated systemic disorders. We here in the report a case of an Arab teen boy, who presented with a sudden loss of vision in his left eye of 1 h duration. The ocular examination revealed acute central retinal artery occlusion. He underwent a series of laboratory and radiological investigations. The blood investigations revealed SCT and abnormal partial thromboplastin time. The fundus fluorescein angiography revealed abnormal retinal vascular perfusion. Marked blood rheological impairment and activation of the coagulation pathway can occur without any contributing factors in SCT leading to severe ocular complications. This is one of the young patients with spontaneous vascular occlusion in SCT.

  5. Nettleship collaterals: circumpapillary cilioretinal anastomoses after occlusion of the central retinal artery.

    PubMed

    Ragge, N K; Hoyt, W F

    1992-03-01

    In extremely rare cases, after occlusion of the central retinal artery, a complete ring of peripapillary anastomotic channels develops. One such case is described and a proposed term given to these channels--'Nettleship collaterals'--after the man who first described them. These collaterals are dilated pathways within the terminal capillary networks of the posterior ciliary arteries and the branches of the central retinal artery. Formation of the channels is believed to be promoted by prelaminar obstruction of the central retinal artery.

  6. N-Acetylcysteine and Acute Retinal Laser Lesion in the Colubrid Snake Eye

    DTIC Science & Technology

    2004-01-01

    immune response to acute laser injury. When we applied a thiol antioxidant, N- acetylcysteine ( NAC ) systemically, after the lesion but before the dyes... acetylcysteine on fluorescence, induced by the dye C-400, in acute retinal laser injury. Dye alone on the left. Dye plus NAC on the right. In the first two...UNCLASSIFIED Defense Technical Information Center Compilation Part Notice ADP020041 TITLE: N- Acetylcysteine and Acute Retinal Laser Lesion in the

  7. Reversibility of retinal ischemia due to central retinal artery occlusion by hyperbaric oxygen

    PubMed Central

    Hadanny, Amir; Maliar, Amit; Fishlev, Gregory; Bechor, Yair; Bergan, Jacob; Friedman, Mony; Avni, Isaac; Efrati, Shai

    2017-01-01

    Purpose Ischemic retinal damage can be reversed by hyperbaric oxygen therapy (HBOT) as long as irreversible infarction damage has not developed. However, the time window till irreversible damage develops is still unknown. The study aim was to evaluate the effect of HBOT and determine possible markers for irreversible retinal damage. Materials and methods Retrospective analysis of 225 patients treated with HBOT for central retinal artery occlusion (CRAO) in 1999–2015. One hundred and twenty-eight patients fulfilled inclusion/exclusion criteria: age >18 years, symptoms <20 hours, and best-corrected visual acuity (BCVA) <0.5 logMAR. Results Time delay from symptoms to treatment was 7.8±3.8 hours. The BCVA was significantly improved after HBOT, from 2.14±0.50 to 1.61±0.78 (P<0.0001). The proportion of patients with clinically meaningful visual improvement was significantly higher in patients without cherry-red spot (CRS) compared to patients with CRS at presentation (86.0% vs 57.6%, P<0.0001). The percentage of patients with final BCVA better than 1.0 was also significantly higher in patients without CRS vs patients with CRS at presentation (61.0% vs 7.1%, P<0.0001). There was no correlation between CRS and the time from symptoms. HBOT was found to be safe, and only 5.5% of patients had minor, reversible, adverse events. Conclusion HBOT is an effective treatment for non-arteritic CRAO as long as CRS has not formed. The fundus findings, rather than the time delay, should be used as a marker for irreversible damage. PMID:28096655

  8. Antiviral selection in the management of acute retinal necrosis

    PubMed Central

    Tam, Patrick MK; Hooper, Claire Y; Lightman, Susan

    2010-01-01

    There is no consensus on the optimal antiviral regimen in the management of acute retinal necrosis, a disease caused by herpetic viruses with devastating consequences for the eye. The current gold standard is based on retrospective case series. Because the incidence of disease is low, few well-designed, randomized trials have evaluated treatment dosage and duration. Newer oral antiviral agents are emerging as alternatives to high-dose intravenous acyclovir, avoiding the need for inpatient intravenous treatment. Drug resistance is uncommon but may also be difficult to identify. Antiviral drugs have few side effects, but special attention needs to be paid to patients who have underlying renal disease, are pregnant or are immunocompromised. PMID:20169044

  9. Acute Hypoglycemia Induces Retinal Cell Death in Mouse

    PubMed Central

    Emery, Martine; Schorderet, Daniel F.; Roduit, Raphaël

    2011-01-01

    Background Glucose is the most important metabolic substrate of the retina and maintenance of normoglycemia is an essential challenge for diabetic patients. Glycemic excursions could lead to cardiovascular disease, nephropathy, neuropathy and retinopathy. A vast body of literature exists on hyperglycemia namely in the field of diabetic retinopathy, but very little is known about the deleterious effect of hypoglycemia. Therefore, we decided to study the role of acute hypoglycemia in mouse retina. Methodology/Principal Findings To test effects of hypoglycemia, we performed a 5-hour hyperinsulinemic/hypoglycemic clamp; to exclude an effect of insulin, we made a hyperinsulinemic/euglycemic clamp as control. We then isolated retinas from each group at different time-points after the clamp to analyze cells apoptosis and genes regulation. In parallel, we used 661W photoreceptor cells to confirm in vivo results. We showed herein that hypoglycemia induced retinal cell death in mouse via caspase 3 activation. We then tested the mRNA expression of glutathione transferase omega 1 (Gsto1) and glutathione peroxidase 3 (Gpx3), two genes involved in glutathione (GSH) homeostasis. The expression of both genes was up-regulated by low glucose, leading to a decrease of reduced glutathione (GSH). In vitro experiments confirmed the low-glucose induction of 661W cell death via superoxide production and activation of caspase 3, which was concomitant with a decrease of GSH content. Moreover, decrease of GSH content by inhibition with buthionine sulphoximine (BSO) at high glucose induced apoptosis, while complementation with extracellular glutathione ethyl ester (GSHee) at low glucose restored GSH level and reduced apoptosis. Conclusions/Significance We showed, for the first time, that acute insulin-induced hypoglycemia leads to caspase 3-dependant retinal cell death with a predominant role of GSH content. PMID:21738719

  10. Central retinal vein occlusion in people aged 40 years or less: a review of 17 patients.

    PubMed Central

    Walters, R F; Spalton, D J

    1990-01-01

    Seventeen patients with central retinal vein occlusion aged 40 or under were reviewed. Ocular involvement was characteristically unilateral, with moderate degrees of retinal haemorrhage, little retinal ischaemia, and a tendency to optic disc swelling. Visual prognosis was good. Follow-up showed that most patients have good general health and no involvement of the fellow eye. There was little evidence to support an inflammatory aetiology or underlying vascular disease in most of the patients. An alternative explanation for the development of CRVO in young patients might be a congenital anomaly of the central retinal vein. PMID:2306442

  11. Retinal Electrophysiology Is a Viable Preclinical Biomarker for Drug Penetrance into the Central Nervous System

    PubMed Central

    Charng, Jason; He, Zheng; Vingrys, Algis J.; Fish, Rebecca L.; Gurrell, Rachel; Bui, Bang V.; Nguyen, Christine T.

    2016-01-01

    Objective. To examine whether retinal electrophysiology is a useful surrogate marker of drug penetrance into the central nervous system (CNS). Materials and Methods. Brain and retinal electrophysiology were assessed with full-field visually evoked potentials and electroretinograms in conscious and anaesthetised rats following systemic or local administrations of centrally penetrant (muscimol) or nonpenetrant (isoguvacine) compounds. Results. Local injections into the eye/brain bypassed the blood neural barriers and produced changes in retinal/brain responses for both drugs. In conscious animals, systemic administration of muscimol resulted in retinal and brain biopotential changes, whereas systemic delivery of isoguvacine did not. General anaesthesia confounded these outcomes. Conclusions. Retinal electrophysiology, when recorded in conscious animals, shows promise as a viable biomarker of drug penetration into the CNS. In contrast, when conducted under anaesthetised conditions confounds can be induced in both cortical and retinal electrophysiological recordings. PMID:27239335

  12. Investigation of retinal morphology alterations using spectral domain optical coherence tomography in a mouse model of retinal branch and central retinal vein occlusion.

    PubMed

    Ebneter, Andreas; Agca, Cavit; Dysli, Chantal; Zinkernagel, Martin S

    2015-01-01

    Retinal vein occlusion is a leading cause of visual impairment. Experimental models of this condition based on laser photocoagulation of retinal veins have been described and extensively exploited in mammals and larger rodents such as the rat. However, few reports exist on the use of this paradigm in the mouse. The objective of this study was to investigate a model of branch and central retinal vein occlusion in the mouse and characterize in vivo longitudinal retinal morphology alterations using spectral domain optical coherence tomography. Retinal veins were experimentally occluded using laser photocoagulation after intravenous application of Rose Bengal, a photo-activator dye enhancing thrombus formation. Depending on the number of veins occluded, variable amounts of capillary dropout were seen on fluorescein angiography. Vascular endothelial growth factor levels were markedly elevated early and peaked at day one. Retinal thickness measurements with spectral domain optical coherence tomography showed significant swelling (p<0.001) compared to baseline, followed by gradual thinning plateauing two weeks after the experimental intervention (p<0.001). Histological findings at day seven correlated with spectral domain optical coherence tomography imaging. The inner layers were predominantly affected by degeneration with the outer nuclear layer and the photoreceptor outer segments largely preserved. The application of this retinal vein occlusion model in the mouse carries several advantages over its use in other larger species, such as access to a vast range of genetically modified animals. Retinal changes after experimental retinal vein occlusion in this mouse model can be non-invasively quantified by spectral domain optical coherence tomography, and may be used to monitor effects of potential therapeutic interventions.

  13. Investigation of Retinal Morphology Alterations Using Spectral Domain Optical Coherence Tomography in a Mouse Model of Retinal Branch and Central Retinal Vein Occlusion

    PubMed Central

    Ebneter, Andreas; Agca, Cavit; Dysli, Chantal; Zinkernagel, Martin S.

    2015-01-01

    Retinal vein occlusion is a leading cause of visual impairment. Experimental models of this condition based on laser photocoagulation of retinal veins have been described and extensively exploited in mammals and larger rodents such as the rat. However, few reports exist on the use of this paradigm in the mouse. The objective of this study was to investigate a model of branch and central retinal vein occlusion in the mouse and characterize in vivo longitudinal retinal morphology alterations using spectral domain optical coherence tomography. Retinal veins were experimentally occluded using laser photocoagulation after intravenous application of Rose Bengal, a photo-activator dye enhancing thrombus formation. Depending on the number of veins occluded, variable amounts of capillary dropout were seen on fluorescein angiography. Vascular endothelial growth factor levels were markedly elevated early and peaked at day one. Retinal thickness measurements with spectral domain optical coherence tomography showed significant swelling (p<0.001) compared to baseline, followed by gradual thinning plateauing two weeks after the experimental intervention (p<0.001). Histological findings at day seven correlated with spectral domain optical coherence tomography imaging. The inner layers were predominantly affected by degeneration with the outer nuclear layer and the photoreceptor outer segments largely preserved. The application of this retinal vein occlusion model in the mouse carries several advantages over its use in other larger species, such as access to a vast range of genetically modified animals. Retinal changes after experimental retinal vein occlusion in this mouse model can be non-invasively quantified by spectral domain optical coherence tomography, and may be used to monitor effects of potential therapeutic interventions. PMID:25775456

  14. Evaluation of Ophthalmic Artery Branch Retrograde Intervention in the Treatment of Central Retinal Artery Occlusion (CRAO)

    PubMed Central

    Wang, Runsheng; Qian, Lu; Wang, Yi; Zheng, Yi; Du, Shanshuang; Lei, Tao; Lv, Peilin; Long, Tan; Wang, Wenjun

    2017-01-01

    Background Central retinal artery occlusion (CRAO) is the occlusion of the central retinal artery resulting in retinal infarction and acute vision loss. Digital subtraction angiography (DSA)–guided superselective ophthalmic artery or selective carotid thrombolysis remains the preferred treatment method for CRAO. This study aimed to evaluate the safety and clinical efficacy of the novel ophthalmic artery branch retrograde thrombolytic intervention for CRAO. Material/Methods Fifty patients with monocular CRAO were enrolled, including 28 males and 22 females (mean age: 55.7±2.3 years). The patients were randomly divided into two groups for thrombolysis with urokinase (400,000 U) and papaverine (30 mg) by either ophthalmic artery branch retrograde intervention (group A, n=26) or superselective ophthalmic artery/selective carotid intervention (group B, n=24). There was no significant difference in age (P=0.58), gender ratio (P=0.49), and time to onset (P=1.00) between the two groups. The adverse reactions and clinical efficacy were evaluated by postoperative DSA, fundus fluorescein angiography (FFA), and visual acuity tests. Results No serious complications, abnormal eye movement, or vitreous hemorrhage occurred in either group. DSA showed that group A had an effective rate (92.30%) comparable to that of group B (100%, χ2=2.08, P=0.25). FFA suggested that both groups had similar treatment efficacy (χ2=3.09, P=0.21). Visual acuity tests also confirmed a similar efficacy of the two intervention approaches (χ2=0.25, P=0.88). Conclusions The developed novel ophthalmic artery branch retrograde intervention is highly effective and safe for CRAO, and may be a superior method compared with the conventional approach. PMID:28064304

  15. [Atypical case of acute retinal necrosis secondary to the primary herpes simplex infection].

    PubMed

    Terelak-Borys, Barbara; Krzyźewska-Niedzialek, Aldona; Jamrozy-Witkowska, Agnieszka; Borkowski, Piotr K; Ulińska, Magdalena; Grabska-Liberek, Iwona

    2015-01-01

    Acute retinal necrosis is a rare manifestation of viral chorioretinitis, accompanied by occlusive vasculitis, which is associated with poor visual prognosis. The main causal factors include varicella-zoster virus in older patients and herpes simplex in younger ones. The disease typically manifests as a reactivation of latent infections. We present a case of a 57-year-old female with atypical clinical manifestation of acute retinal necrosis secondary to the primary viral infection with herpes simplex. The serology panel of vitreous tap and blood sample confirmed viral aetiology (H. simplex). The initial clinical signs included optic disc edema with retinitis presenting as self-limiting, slowly progressing, peripheral lesions, later followed by uveitis. The antiviral therapy resolved the symptoms of uveitis and enabled healing of retinal lesions, however the natural course of disease was later complicated with retinal detachment. It was successfully treated with vitreoretinal surgery. Despite aggressive treatment, the final visual outcome was unfavourable, due to optic nerve atrophy.

  16. Nettleship collaterals: circumpapillary cilioretinal anastomoses after occlusion of the central retinal artery.

    PubMed Central

    Ragge, N K; Hoyt, W F

    1992-01-01

    In extremely rare cases, after occlusion of the central retinal artery, a complete ring of peripapillary anastomotic channels develops. One such case is described and a proposed term given to these channels--'Nettleship collaterals'--after the man who first described them. These collaterals are dilated pathways within the terminal capillary networks of the posterior ciliary arteries and the branches of the central retinal artery. Formation of the channels is believed to be promoted by prelaminar obstruction of the central retinal artery. Images PMID:1540571

  17. Iatrogenic central retinal artery occlusion after carotid body tumor embolization and excision

    PubMed Central

    Rangel, Carlos M.; Jaramillo, Sergio; Varón, Clara L.; Prada, Angélica M.

    2017-01-01

    Objective: To report a case of iatrogenic central retinal artery occlusion after embolization and surgical resection of carotid body paraganglioma. Methods: Case report Results: One adult female patient presented with persistent unilateral visual loss after embolization with Embosphere® and Contour® microparticles of carotid body tumor. Fluorescein angiography revealed intraluminal microspheres in the central retinal artery ramifications. OCT revealed intraretinal spherical, hyporeflective particles with posterior shadowing. Conclusions: Central retinal artery occlusion should be assessed as a possible complication after surgical repair of head and neck paragangliomas.

  18. Acute retinal necrosis complicating chicken pox in a healthy adult: a case report and review of literature.

    PubMed

    Tajunisah, Iqbal; Reddy, Sagili Chandrasekhara

    2007-01-01

    We report a case of unilateral acute retinal necrosis (ARN) with marked vitritis and retinal necrosis leading to retinal breaks following chicken pox successfully treated with intravenous acyclovir followed by oral acyclovir, orbital floor triamcinolone injections to contain the inflammation, and barrier laser therapy to secure the retinal breaks with good visual outcome. This case is unusual in its severity and the novel use orbital floor triamcinolone therapy to contain ARN inflammation.

  19. A method and technical equipment for an acute human trial to evaluate retinal implant technology

    NASA Astrophysics Data System (ADS)

    Hornig, Ralf; Laube, Thomas; Walter, Peter; Velikay-Parel, Michaela; Bornfeld, Norbert; Feucht, Matthias; Akguel, Harun; Rössler, Gernot; Alteheld, Nils; Lütke Notarp, Dietmar; Wyatt, John; Richard, Gisbert

    2005-03-01

    This paper reports on methods and technical equipment to investigate the epiretinal stimulation of the retina in blind human subjects in acute trials. Current is applied to the retina through a thin, flexible microcontact film (microelectrode array) with electrode diameters ranging from 50 to 360 µm. The film is mounted in a custom-designed surgical tool that is hand-held by the surgeon during stimulation. The eventual goal of the work is the development of a chronically implantable retinal prosthesis to restore a useful level of vision to patients who are blind with outer retinal degenerations, specifically retinitis pigmentosa and macular degeneration.

  20. Association between retinal hemorrhagic pattern and macular perfusion status in eyes with acute branch retinal vein occlusion

    PubMed Central

    Muraoka, Yuki; Uji, Akihito; Tsujikawa, Akitaka; Murakami, Tomoaki; Ooto, Sotaro; Suzuma, Kiyoshi; Takahashi, Ayako; Iida, Yuto; Miwa, Yuko; Hata, Masayuki; Yoshimura, Nagahisa

    2016-01-01

    This prospective study included 63 eyes with acute branch retinal vein occlusion (BRVO) to evaluate the retinal hemorrhagic patterns at the posterior poles and explore their clinical relevance in macular perfusion differentiation. Retinal hemorrhagic patterns and macular perfusion status were evaluated via fundus photography and fluorescein angiography, respectively. Macular perfusion was judged as nonischemic in 30, ischemic in 28, and undeterminable in 5 among the 63 eyes. Predominant hemorrhagic patterns were flame-shaped in 39 (67.2%) and non-flame-shaped in 19 (32.8%) eyes. All 39 eyes with a flame-shaped hemorrhage showed a nonischemic macula. Of the 19 eyes classified as having a non-flame-shaped hemorrhage, 13 (68.4%) had an ischemic macula and 6 (31.6%) had a nonischemic macula (P < 0.001). Parallelism in eyes with a flame-shaped hemorrhage was higher than in those with a non-flame-shaped hemorrhage (P < 0.001), and in those with a nonischemic macula versus those with an ischemic macula (P < 0.001). The area under the curve for parallelism was 0.975 (P < 0.001), suggesting an accurate diagnostic parameter for macular perfusion differentiation. In conclusion, we objectively evaluated retinal hemorrhagic patterns at the posterior pole in BRVO using the parallelism method, which was useful in differentiating macular perfusion status. PMID:27334338

  1. Retinal oximetry measures systemic hypoxia in central nervous system vessels in chronic obstructive pulmonary disease

    PubMed Central

    Bragason, David; Hardarson, Sveinn Hakon; Vacchiano, Charles; Gislason, Thorarinn; Kristjansdottir, Jona Valgerdur; Kristjansdottir, Gudrun; Stefánsson, Einar

    2017-01-01

    Background Determination of the blood oxyhemoglobin saturation in the retinal vessels of the eye can be achieved through spectrophotometric retinal oximetry which provides access to the state of oxyhemoglobin saturation in the central nervous system circulation. The purpose of this study was to test the capability of the Oxymap T1 oximeter to detect systemic hypoxemia and the effect of supplemental oxygen on retinal vessel oxyhemoglobin saturation. Methods Oxygen saturation of hemoglobin in retinal arterioles and venules was measured in 11 subjects with severe chronic obstructive pulmonary disease (COPD) on long term oxygen therapy. Measurements were made with and without their daily supplemental oxygen. Eleven healthy age and gender matched subjects were measured during ambient air breathing for comparison of oxyhemoglobin saturation in retinal arterioles and venules. Retinal arteriolar oxyhemoglobin saturation in COPD subjects inspiring ambient air was compared with finger pulse oximetry and blood samples from radial artery. Results COPD subjects had significantly lower oxyhemoglobin saturation during ambient air breathing than healthy controls in both retinal arterioles (87.2%±4.9% vs. 93.4%±4.3%, p = 0.02; n = 11) and venules (45.0%±10.3% vs. 55.2%±5.5%, p = 0.01). Administration of their prescribed supplemental oxygen increased oxyhemoglobin saturation in retinal arterioles (87.2%±4.9% to 89.5%±6.0%, p = 0.02) but not in venules (45.0%±10.3% to 46.7%±12.8%, p = 0.3). Retinal oximetry values were slightly lower than radial artery blood values (mean percentage points difference = -5.0±5.4, 95% CI: -15.68 to 5.67) and finger pulse oximetry values (-3.1±5.5, 95% CI: -14.05 to 7.84). Conclusions The noninvasive Oxymap T1 retinal oximetry detects hypoxemia in central nervous system vessels in patients with severe COPD compared with healthy controls. The instrument is sensitive to changes in oxygen breathing but displays slightly lower measures than finger

  2. Intra-arterial Thrombolysis for Central Retinal Artery Occlusion after the Coil Embolization of Paraclinoid Aneurysm

    PubMed Central

    Yoo, Minwook; Kim, Hae Yu; Choi, Byeong-Sam

    2016-01-01

    The most common complication of coil embolization for cerebral aneurysms is thrombo-embolic stroke; in rare cases, these strokes, can present with central retinal artery occlusion. At our institution, a 53-year-old woman underwent stent-assisted coiling of the aneurysm. The patient's vision was improved immediately after intra-arterial thrombolysis and had further improved 8 months later. This report describes our experience of a rare case of central retinal artery occlusion after coil embolization that was successfully treated by intra-arterial thrombolysis. PMID:28184347

  3. Central respiratory failure during acute organophosphate poisoning.

    PubMed

    Carey, Jennifer L; Dunn, Courtney; Gaspari, Romolo J

    2013-11-01

    Organophosphate (OP) pesticide poisoning is a global health problem with over 250,000 deaths per year. OPs affect neuronal signaling through acetylcholine (Ach) neurotransmission via inhibition of acetylcholinesterase (AChE), leading to accumulation of Ach at the synaptic cleft and excessive stimulation at post-synaptic receptors. Mortality due to OP agents is attributed to respiratory dysfunction, including central apnea. Cholinergic circuits are integral to many aspects of the central control of respiration, however it is unclear which mechanisms predominate during acute OP intoxication. A more complete understanding of the cholinergic aspects of both respiratory control as well as neural modification of pulmonary function is needed to better understand OP-induced respiratory dysfunction. In this article, we review the physiologic mechanisms of acute OP exposure in the context of the known cholinergic contributions to the central control of respiration. We also discuss the potential central cholinergic contributions to the known peripheral physiologic effects of OP intoxication.

  4. Acute Retinal Necrosis Presenting in Developmentally-delayed Patients with Neonatal Encephalitis: A Case Series and Literature Review.

    PubMed

    Okafor, Kingsley; Lu, Jonathan; Thinda, Sumeer; Schwab, Ivan; Morse, Lawrence S; Park, Susanna S; Moshiri, Ala

    2016-05-18

    We report three cases of patients with developmental-delay from neonatal herpetic encephalitis and/or meningitis who presented years later with acute retinal necrosis due to herpes simplex virus. The diagnosis was delayed in all cases due to the patients' inability to verbalize their ocular complaints and cooperate with eye examinations. This case series documents the clinical course, pathophysiologic mechanism, and treatment of acute retinal necrosis in this patient population. Clinicians should understand the importance of prudent consideration of acute retinal necrosis in patients with a history of neonatal herpetic encephalitis and/or meningitis presenting with a red eye.

  5. Activated protein C resistance in patients with central retinal vein occlusion

    PubMed Central

    Larsson, J; Sellman, A; Bauer, B

    1997-01-01

    AIM/BACKGROUND—A new defect in the anticoagulant system has recently been discovered—activated protein C resistance. The frequency of this disorder has been shown to be increased in young patients (<50 years of age) with central retinal vein occlusion. This study was carried out to determine if there was any overrepresentation of activated protein C resistance in patients >50 years of age with central retinal vein occlusion.
METHODS—Blood samples were obtained from 83 patients >50 years of age and with a history of central retinal vein occlusion. The blood samples were analysed for activated protein C resistance with standard clinical laboratory methods.
RESULTS—In this material 11% of the patients were resistant to activated protein C. The normal incidence of activated protein C resistance in the same geographical area is 10-11%.
CONCLUSION—Activated protein C resistance does not seem to be a cause of central retinal vein occlusion in people older than 50 years.

 PMID:9486021

  6. N-acetylcysteine and acute retinal laser lesions in the colubrid snake eye

    NASA Astrophysics Data System (ADS)

    Elliott, William R., III; Rentmeister-Bryant, Heike K.; Barsalou, Norman; Beer, Jeremy; Zwick, Harry

    2004-07-01

    This study examined the role of oxidative stress and the effect of a single dose treatment with N-Acetylcysteine (NAC) on the temporal development of acute laser-induced retinal injury. We used the snake eye/Scanning Laser Ophthalmoscope (SLO) model, an in vivo, non-invasive ocular imaging technique, which has the ability to image cellular retinal detail and allows for studying morphological changes of retinal injury over time. For this study 12 corn-snakes (Elaphe g. guttata) received 5 laser exposures per eye, followed by either a single dose of the antioxidant NAC (150mg/kg, IP in sterile saline) or placebo. Laser exposures were made with a Nd: VO4 DPSS, 532nm laser, coaxially aligned to the SLO. Shuttered pulses were 20msec x 50 mW; 1mJ each. Retinal images were taken using a Rodenstock cSLO and were digitally recorded at 1, 6, 24-hrs, and at 3-wks post-exposure. Lesions were assessed by two raters blind to the conditions of the study yielding measures of damaged area and counts of missing or damaged photoreceptors. Treated eyes showed a significant beneficial effect overall, and these results suggest that oxidative stress plays a role in laser-induced retinal injury. The use of NAC or a similar antioxidant shows promise as a therapeutic tool.

  7. Central retinal vein occlusion in a patient on hemodialysis secondary to antiphospholipid syndrome: Case report.

    PubMed

    Jabrane, Marouane; Ez-Zahraoui, Med Reda; Hajji, Ibtissam; Fadili, Wafaa; Moutaouakil, Abdeljalil; Laouad, Inass

    2017-02-08

    Central retinal vein occlusion (CRVO) is one of the most common retinal vascular disease. Macular edema associated is responsible of the major decrease in visual acuity. The main causes often implicated are high blood pressure and diabetes. Other etiologies should be sought including CRVO secondary to antiphospholipid syndrome (APS). This rare etiology is associated with a poor prognosis when late diagnosed. Owing to the high associated mortality, early diagnosis and prompt treatment are necessary. We describe a case of APS complicated by a catastrophic antiphospholipid syndrome in a patient who presented a decrease visual acuity.

  8. Central retinal artery occlusion following forehead injection with a corticosteroid suspension.

    PubMed

    Edwards, Albert O

    2008-01-01

    Intralesional injection of corticosteroid suspensions into or adjacent to the ocular adnexa is performed by a number of medical specialists including dermatologists. Although not widely known outside of the ophthalmic community, these injections can lead to blindness through embolization of the central retinal artery. A case of blindness following injection into the forehead lesion of a child with the rare dermatologic condition pyogenic arthritis and pyodermic gangrenosum syndrome is reported. Injection into or near the ocular adnexa may be performed in small boluses to reduce the chance of retinal embolization following entry into the arterial system.

  9. Central retinal artery occlusion in association with fibromuscular dysplasia

    PubMed Central

    Altun, Ahmet; Altun, Gulengul; Olcaysu, Osman Okan; Kurna, Sevda Aydin; Aki, Suat Fazil

    2013-01-01

    A 14 year-old female, whose chief complaint was severe vision loss in the right eye for 2 days, presented to the Clinic of Ophthalmology of Fatih Sultan Mehmet Education and Research Hospital. The patient had been attending follow-up visits for 4 years, following a diagnosis of fibromuscular dysplasia by the Clinic of Pediatrics. The patient underwent a complete ophthalmo-logic, angiographic, hematologic, and systemic evaluation. Fundus fluorescein angiography was performed immediately, because of the cherry-red spot sign in the macula of the right eye. Fundus fluorescein angiography revealed evidence of marked stasis of the retinal arterial circulation in the right eye. Best corrected visual acuity was 20/400 in the right eye and 20/20 in the left eye. PMID:24293990

  10. Central retinal artery occlusion in association with fibromuscular dysplasia.

    PubMed

    Altun, Ahmet; Altun, Gulengul; Olcaysu, Osman Okan; Kurna, Sevda Aydin; Aki, Suat Fazil

    2013-01-01

    A 14 year-old female, whose chief complaint was severe vision loss in the right eye for 2 days, presented to the Clinic of Ophthalmology of Fatih Sultan Mehmet Education and Research Hospital. The patient had been attending follow-up visits for 4 years, following a diagnosis of fibromuscular dysplasia by the Clinic of Pediatrics. The patient underwent a complete ophthalmo-logic, angiographic, hematologic, and systemic evaluation. Fundus fluorescein angiography was performed immediately, because of the cherry-red spot sign in the macula of the right eye. Fundus fluorescein angiography revealed evidence of marked stasis of the retinal arterial circulation in the right eye. Best corrected visual acuity was 20/400 in the right eye and 20/20 in the left eye.

  11. Comparison of optical coherence tomography findings in a patient with central retinal artery occlusion in one eye and end-stage glaucoma in the fellow eye.

    PubMed

    Greene, Daniel P; Richards, Charles P; Ghazi, Nicola G

    2012-01-01

    This case describes a patient with chronic central retinal artery occlusion in one eye and end-stage traumatic glaucoma in the fellow eye. Optical coherence tomography (OCT) of the macula of the chronic phase of central retinal artery occlusion of the right eye indicated loss of the normal foveal depression, extensive inner retinal atrophy, and marked retinal thinning. In contrast, scans of the left eye with end-stage glaucoma demonstrated an intact foveal depression and limited retinal thinning. The pattern of macular OCT findings in this patient illustrates distinguishing features between chronic central retinal artery occlusion and chronic optic neuropathy due to end-stage glaucoma.

  12. A serial study of retinal changes following optic neuritis with sample size estimates for acute neuroprotection trials.

    PubMed

    Henderson, Andrew P D; Altmann, Daniel R; Trip, Anand S; Kallis, Constantinos; Jones, Steve J; Schlottmann, Patricio G; Garway-Heath, David F; Plant, Gordon T; Miller, David H

    2010-09-01

    Following an episode of optic neuritis, thinning of the retinal nerve fibre layer, which indicates axonal loss, is observed using optical coherence tomography. The longitudinal course of the retinal changes has not been well characterized. We performed a serial optical coherence tomography study in patients presenting with optic neuritis in order to define the temporal evolution of retinal nerve fibre layer changes and to estimate sample sizes for proof-of-concept trials of neuroprotection using retinal nerve fibre layer loss as the outcome measure. Twenty-three patients (7 male, 16 female, mean age 31 years) with acute clinically isolated unilateral optic neuritis were recruited to undergo optical coherence tomography, visual assessments and visual evoked potentials at presentation (median 16 days from onset of visual loss) and after 3, 6, 12 and 18 months. Compared with the clinically unaffected fellow eye, the retinal nerve fibre layer thickness of the affected eye was significantly increased at presentation and significantly reduced at all later time points. The evolution of retinal nerve fibre layer changes in the affected eye fitted well with an exponential model, with thinning appearing a mean of 1.6 months from symptom onset and the rate of ongoing retinal nerve fibre layer loss decreasing thereafter. At presentation, increased retinal nerve fibre layer thickness was associated with impaired visual acuity and prolonged visual evoked potential latency. Visual function after 12 months was not related to the extent of acute retinal nerve fibre layer swelling but was significantly associated with the extent of concurrent retinal nerve fibre layer loss. Sample size calculations for placebo-controlled trials of acute neuroprotection indicated that the numbers needed after 6 months of follow up are smaller than those after 3 months and similar to those after 12 months of follow-up. Study power was greater when investigating differences between clinically

  13. Age and sex distribution of some retinal macular diseases: senile and presenile macular degeneration and central serous retinitis.

    PubMed

    Knave, B; Tengroth, B; Voss, M

    1984-01-01

    The age and sex distribution of senile macular degeneration (SMD) was investigated at the Low Vision Clinic in Stockholm. SMD increased with age and was found to be more common among women than men. This difference was not due to the fact that women live longer than men or related to women consulting ophthalmologists more often than men because of visual handicap. The age and sex distribution of presenile macular degeneration ( PSMD ) and central serous retinitis (CSR) was investigated at the Department of Ophthalmology of Falun Hospital. Also PSMD increased with age and was found to be more common among women than men, even if the sex difference was not as clear as for SMD. CSR was found to be more frequent at younger ages and, contrary to SMD and PSMD , more common among men. The reasons for these sex differences in frequencies of SMD, PSMD and CSR are not known.

  14. Central projections of intrinsically photosensitive retinal ganglion cells in the macaque monkey.

    PubMed

    Hannibal, J; Kankipati, L; Strang, C E; Peterson, B B; Dacey, D; Gamlin, P D

    2014-07-01

    Circadian rhythms generated by the suprachiasmatic nucleus (SCN) are entrained to the environmental light/dark cycle via intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment melanopsin and the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP). The ipRGCs regulate other nonimage-forming visual functions such as the pupillary light reflex, masking behavior, and light-induced melatonin suppression. To evaluate whether PACAP-immunoreactive retinal projections are useful as a marker for central projection of ipRGCs in the monkey brain, we characterized the occurrence of PACAP in melanopsin-expressing ipRGCs and in the retinal target areas in the brain visualized by the anterograde tracer cholera toxin subunit B (CtB) in combination with PACAP staining. In the retina, PACAP and melanopsin were found to be costored in 99% of melanopsin-expressing cells characterized as inner and outer stratifying melanopsin RGCs. Two macaque monkeys were anesthetized and received a unilateral intravitreal injection of CtB. Bilateral retinal projections containing colocalized CtB and PACAP immunostaining were identified in the SCN, the lateral geniculate complex including the pregeniculate nucleus, the pretectal olivary nucleus, the nucleus of the optic tract, the brachium of the superior colliculus, and the superior colliculus. In conclusion, PACAP-immunoreactive projections with colocalized CtB represent retinal projections of ipRGCs in the macaque monkey, supporting previous retrograde tracer studies demonstrating that melanopsin-containing retinal projections reach areas in the primate brain involved in both image- and nonimage-forming visual processing.

  15. Acute Retinal Necrosis Associated with Epstein-Barr Virus in a Patient Undergoing Immunosuppressive Therapy

    PubMed Central

    Oe, Chiaki; Hiraoka, Miki; Tanaka, Sachie; Ohguro, Hiroshi

    2016-01-01

    Acute retinal necrosis (ARN) is a rapidly progressive and severe retinitis resulting in a poor visual outcome. Infections caused by herpes viruses such as herpes simplex virus (HSV) types 1 and 2 or the varicella zoster virus (VZV) are known to be implicated in the development of ARN. In the present study, an 80-year-old female with ARN was examined. She had been affected with rheumatoid arthritis and had taken methotrexate for over 10 years. Her right eye showed clinical features of ARN, and her left eye showed mild retinitis. The genomic DNA in the aqueous humor and vitreous fluid from her right eye were analyzed by a comprehensive polymerase chain reaction (PCR) assay to screen infectious pathogens including viruses. The Epstein-Barr virus (EBV) was detected from both specimens, but neither HSV or VZV nor cytomegalovirus was detected. She underwent intraocular surgery following systemic corticosteroid and acyclovir applications. However, although the retinitis of her right eye was extinguished, the final visual outcome was blindness due to optic nerve atrophy. There are few reports indicating that EBV is associated with ARN development. The present findings suggest that EBV alone can be the causative agent of ARN. PMID:27194989

  16. Sulfur Mustard Exposure and Non-Ischemic Central Retinal Vein Occlusion

    PubMed Central

    Shoeibi, Nasser; Balali-Mood, Mahdi; Abrishami, Mojtaba

    2016-01-01

    A 41-year-old man was referred with a complaint of visual loss in his left eye and his best corrected visual acuity was 20/80. Slit lamp examination showed arborizing conjunctival vessels and dry eye. Fundus examination and fluorescein angiography revealed a non-ischemic central retinal vein occlusion. Cardiovascular, rheumatologic, and hematologic work up showed no abnormal findings. An ascertained history of exposure to sulfur mustard during the Iran-Iraq war was documented in his medical history. Four sessions of intravitreal bevacizumab injections were done as needed. After two-year follow-up, visual acuity in his left eye improved to 20/25 and macular edema was resolved without any need for further interventions. We conclude that sulfur mustard gas exposure may be considered as a predisposing factor for central retinal vein occlusion, as was found in our patient (an Iranian war veteran) by excluding all yet known etiologies and predisposing factors. PMID:26722147

  17. Epigenetic intervention with a BET inhibitor ameliorates acute retinal ganglion cell death in mice

    PubMed Central

    Li, Jun; Zhao, Lei; Urabe, Go; Fu, Yingmei

    2017-01-01

    Purpose The bromo and extraterminal (BET) epigenetic “reader” family is becoming an appealing new therapeutic target for several common diseases, yet little is known of its role in retinal neurodegeneration. We explored the potential of BET inhibition in the protection of retinal ganglion cells (RGCs). Methods To test the therapeutic effect of JQ1, an inhibitor highly selective for the BET family of proteins, we used an acute RGC damage model induced by N-methyl-D-aspartic acid (NMDA) excitotoxicity. Adult C57BL/6 mice received an intravitreal injection of NMDA with (or without) JQ1 in one eye and vehicle control in the contralateral eye; RGC loss was assessed on retinal sections and whole mounts. Gene expression and apoptosis were analyzed by quantitative real time (RT)-PCR and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), respectively. For counting RGCs, immunostaining of the marker protein BRN3A was performed on whole mounts. Results NMDA treatment eliminated RGCs (day 7 and day 14 post injection) and diminished the expression (mRNAs) of RGC-selective genes, including Thy1, Nrn1, Sncg, and Nfl (day 3 and day 7). In contrast, co-injection with JQ1 maintained the number and gene expression of RGCs at ~2 fold of the control (NMDA only, no JQ1), and it decreased NMDA-induced TUNEL-positive cells in the RGC layer by 35%. While NMDA treatment dramatically upregulated mRNAs of inflammatory cytokines (TNFα, IL-1β, MCP-1, RANTES) in retinal homogenates, co-injection with JQ1 suppressed their upregulation by ~50%. Conclusions Intravitreal injection of a BET inhibitor (JQ1) ameliorates NMDA-induced RGC death, revealing the RGC-protective potential of pharmacological blockage of the BET family. This new strategy of epigenetic intervention may be extended to other retinal degenerative conditions. PMID:28356707

  18. Treatment of recent onset central retinal vein occlusion with intravitreal tissue plasminogen activator: a pilot study

    PubMed Central

    Glacet-Bernard, A.; Kuhn, D.; Vine, A.; Oubraham, H.; Coscas, G.; Soubrane, G.

    2000-01-01

    AIMS—To study the effects of intravitreal tissue plasminogen activator (tPA) in recent onset central retinal vein occlusion (CRVO).
METHODS—15 patients with recent onset CRVO (from 1-21 days' duration, mean 8 days) were given 75-100 µg of tPA intravitreally associate with low dose low molecular weight heparin. CRVO was perfused in nine patients and with mild ischaemia not exceeding 100 disc diameters in six patients. Follow up ranged from 5 to 21 months for 14 patients (mean 8 months). Visual acuity measurement, macular threshold (Humphrey perimeter), fluorescein angiography with the scanning laser ophthalmoscope with special emphasis on retinal circulation times, and retinal perfusion were performed at days 0, 1, and 8 and months 1, 3, and 6.
RESULTS—Visual acuity was significantly improved on the first day after treatment in only one eye, and decreased transiently in six eyes (40%). Retinal blood velocity was not significantly modified by tPA injection. Retinal ischaemia developed in six eyes (43%), leading to panretinal photocoagulation in five eyes including one with rubeosis iridis. At the end of follow up, visual acuity had improved to 20/30 or better in five eyes (36%), including two with complete recovery; visual acuity was worse than 20/200 in three eyes (28%). No complication of tPA injection was observed.
CONCLUSION—Intravitreal tPA treatment for CRVO appears to be simple and safe, but did not significantly modify the course of the occlusion in our patients immediately after treatment. Final visual outcome did not differ significantly from that observed in the natural course of the disease, but final visual acuity seemed to be slightly better. A randomised study is required to determine if intravitreal tPA actually improves visual outcome in CRVO.

 PMID:10837386

  19. Hereditary retinal eye diseases in childhood and youth affecting the central retina.

    PubMed

    Nentwich, Martin M; Rudolph, Guenther

    2013-09-01

    Hereditary dystrophies affecting the central retina represent a heterogeneous group of diseases. Mutations in different genes may be responsible for changes of the choroid (choroideremia), of the retinal pigment epithelium [RPE] (Best's disease), of the photoreceptor outer segments (Stargardt's disease) and of the bipolar and Mueller cells (x-linked retinoschisis). The correct diagnosis of hereditary retinal dystrophies is important, even though therapeutic options are limited at the moment, as every patient should get a diagnosis and be informed about the expected prognosis. Furthermore, specific gene therapy of a number of diseases such as Leber congenital amaurosis, choroideremia, Stargardt's disease, Usher Syndrome and achromatopsia is being evaluated at present. Classic examinations for patients suffering from hereditary retinal dystrophies of the central retina are funduscopy - also using red-free light - visual-field tests, electrophysiologic tests as electro-retinogram [ERG] and multifocal ERG and tests evaluating color vision. Recently, new imaging modalities have been introduced into the clinical practice. The significance of these new methods such as high-resolution spectral-domain optic coherence tomography [SD-OCT] and fundus autofluorescence will be discussed as well as "next generation sequencing" as a new method for the analysis of genetic mutations in a larger number of patients.

  20. Are Preexisting Retinal and Central Nervous System-Related Comorbidities Risk Factors for Complications Following Robotic-Assisted Laparoscopic Prostatectomy?

    PubMed Central

    Chalmers, David; Cusano, Antonio; Haddock, Peter; Staff, Ilene; Wagner, Joseph

    2015-01-01

    ABSTRACT Purpose: To assess whether retinal and central nervous system (CNS) comorbidities are risk factors for complications following robotic assisted laparoscopic prostatectomy (RALP). Materials and Methods: A retrospective review of our RALP database identified 1868 patients who underwent RALP by a single surgeon between December 10, 2003-March 14, 2014. We hypothesized that patients with preexisting retinal or CNS comorbidities were at a greater risk of suffering retinal and CNS complications following RALP. Perioperative complications and risk of recurrence were graded using the Clavien and D'Amico systems, respectively. Results: 40 (2.1%) patients had retinal or CNS-related comorbidities, of which 15 had a history of retinal surgery and 24 had a history of cerebrovascular accident, aneurysm and/or neurosurgery. One additional patient had a history of both retinal and CNS events. Patients with retinal or CNS comorbidities were significantly older, had elevated PSA levels and CCI (Charlson Comorbidity Index) scores than the control group. Blood loss, length of stay, surgical duration, BMI, diagnostic Gleason score and T-stage were not statistically different between groups. No retinal or CNS complications occurred in either group. The distribution of patients between D'Amico risk categories was not statistically different between the groups. There was also no difference in the incidence of total complications between the groups. Conclusions: RALP-associated retinal and CNS complications are rare. While our RALP database is large, the cohort of patients with retinal or CNS-related comorbidities was relatively small. Our dataset suggests retinal and CNS pathology presents no greater risk of suffering from perioperative complications following RALP. PMID:26401857

  1. Calpain Inhibition Attenuates Apoptosis of Retinal Ganglion Cells in Acute Optic Neuritis

    PubMed Central

    Smith, Amena W.; Das, Arabinda; Guyton, M. Kelly; Ray, Swapan K.; Rohrer, Baerbel

    2011-01-01

    Purpose. Optic neuritis (ON), inflammation of the optic nerve, is strongly associated with the pathogenesis of multiple sclerosis (MS) and is initiated by the attack of autoreactive T cells against self-myelin antigens, resulting in demyelination, degeneration of retinal ganglion cells (RGCs), and cumulative visual impairment. Methods. Experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats on day 0, and animals received daily intraperitoneal injections of calpain inhibitor (calpeptin) or vehicle from day 1 until killed. Retinal cell death was analyzed by DNA fragmentation, and surviving ganglion cells were quantified after double labeling of retinal tissue with TUNEL and Brn3a. The expression of apoptotic and inflammatory proteins was determined by Western blotting. Results. It was demonstrated that calpain inhibition downregulates expression of proapoptotic proteins and the proinflammatory molecule nuclear factor-kappa B (NF-κB) in the retina of Lewis rats with acute EAE. Immunofluorescent labeling revealed that apoptotic cells in the RGC layer of vehicle-treated EAE animals were Brn3a positive, and a moderate dose of calpeptin dramatically reduced the frequency of apoptotic RGCs. Conclusions. These results suggest that calpain inhibition might be a useful supplement to immunomodulatory therapies such as corticosteroids in ON, due to its neuroprotective effect on RGCs. PMID:21613375

  2. Acute cyanide intoxication and central transmitter systems.

    PubMed

    Persson, S A; Cassel, G; Sellström, A

    1985-12-01

    In rats treated with sodium cyanide (5-20 mg/kg, ip) dopamine was dose dependently decreased in the striatum within 60 sec. One of the main metabolites of dopamine in the central nervous system, 3-methoxy-4-hydroxyphenylacetic acid (HVA), was decreased in striatum, olfactory tubercle, and hippocampus. However, the oxidatively deaminated metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), was not significantly altered in any of the brain regions studied. Naturally occurring levels of 3,4-dihydroxy-L-phenylalanine (L-dopa), as well as L-dopa accumulated after inhibition of the neuronal L-aromatic amino acid decarboxylase, increased in cyanide-treated rats. The dopamine receptor antagonist spiperone (0.05 mg/kg, ip) slightly increased the survival in acute cyanide intoxication. Sodium cyanide increased the levels of glutamine in frontal cortex and striatum at all doses studied. Glutamic acid was increased in the cerebellum, striatum, and hippocampus after sodium cyanide (5-10 mg/kg, ip). Higher doses decreased glutamic acid in the cerebellum, the frontal cortex, and the striatum. gamma-Aminobutyric acid (GABA) concentrations were diminished at high doses in all regions studied. Cyanide increased the levels of cyclic GMP in the cerebellum. In the striatum cyclic GMP was decreased after sodium cyanide (10 and 20 mg/kg). No significant alterations in the concentrations of acetylcholine or choline were seen in the striatum of cyanide-treated rats. The acetylcholinesterase inhibitor physostigmine and the muscarinic receptor antagonist atropine decreased the survival of mice given sodium cyanide. Acute cyanide intoxication thus produces rapid and fairly specific changes in central dopaminergic and GABA-ergic pathways.

  3. Acute intensive insulin therapy exacerbates diabetic blood-retinal barrier breakdown via hypoxia-inducible factor-1α and VEGF

    PubMed Central

    Poulaki, Vassiliki; Qin, Wenying; Joussen, Antonia M.; Hurlbut, Peter; Wiegand, Stanley J.; Rudge, John; Yancopoulos, George D.; Adamis, Anthony P.

    2002-01-01

    Acute intensive insulin therapy is an independent risk factor for diabetic retinopathy. Here we demonstrate that acute intensive insulin therapy markedly increases VEGF mRNA and protein levels in the retinae of diabetic rats. Retinal nuclear extracts from insulin-treated rats contain higher hypoxia-inducible factor-1α (HIF-1α) levels and demonstrate increased HIF-1α–dependent binding to hypoxia-responsive elements in the VEGF promoter. Blood-retinal barrier breakdown is markedly increased with acute intensive insulin therapy but can be reversed by treating animals with a fusion protein containing a soluble form of the VEGF receptor Flt; a control fusion protein has no such protective effect. The insulin-induced retinal HIF-1α and VEGF increases and the related blood-retinal barrier breakdown are suppressed by inhibitors of p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol (PI) 3-kinase, but not inhibitors of p42/p44 MAPK or protein kinase C. Taken together, these findings indicate that acute intensive insulin therapy produces a transient worsening of diabetic blood-retinal barrier breakdown via an HIF-1α–mediated increase in retinal VEGF expression. Insulin-induced VEGF expression requires p38 MAPK and PI 3-kinase, whereas hyperglycemia-induced VEGF expression is HIF-1α–independent and requires PKC and p42/p44 MAPK. To our knowledge, these data are the first to identify a specific mechanism for the transient worsening of diabetic retinopathy, specifically blood-retinal barrier breakdown, that follows the institution of intensive insulin therapy. PMID:11901189

  4. Frosted Branch Angiitis Secondary to Familial Mediterranean Fever Resembling Central Retinal Vein Occlusion

    PubMed Central

    Ozdal, Pınar Çakar; Teke, Mehmet Yasin

    2016-01-01

    Purpose. To report a case of unilateral frosted branch angiitis (FBA) resembling central retinal vein occlusion associated with Familial Mediterranean Fever (FMF). Case Report. A 32-year-old woman presented with progressive, painless vision loss in her left eye lasting for 2 days. She was clinically diagnosed with FMF 2 months ago. The best-corrected visual acuity (BCVA) was 20/20 in her right eye and there was light perception in the left. Ophthalmologic examination revealed severe retinal vasculitis showing clinical features of FBA in the left eye. 64 mg/day oral methylprednisolone was started. A significant improvement in retinal vasculitis was observed in two weeks. However, BCVA did not increase significantly due to subhyaloid premacular hemorrhage. Argon laser posterior hyaloidotomy was performed. One week after hyaloidotomy, visual acuity improved to 20/20 and intravitreal hemorrhage disappeared. Four months after the first attack, FBA recurred. Oral methylprednisolone dosage was increased to 64 mg/day and combined with azathioprine 150 mg. At the end of 12-month follow-up, the BCVA was 20/25 and development of epiretinal membrane was observed in the left eye. Conclusions. Frosted branch angiitis may occur with gene abnormalities as an underlying condition. Our case showed that FMF might be a causative disease. PMID:28044118

  5. Central Retinal Venous Pressure in Eyes of Normal-Tension Glaucoma Patients with Optic Disc Hemorrhage

    PubMed Central

    Kim, Ko Eun; Kim, Dong Myung; Flammer, Josef; Kim, Kyoung Nam

    2015-01-01

    Objective To compare central retinal venous pressure (CRVP) among eyes with and without optic disc hemorrhage (ODH) in bilateral normal-tension glaucoma (NTG) patients and NTG eyes without an episode of ODH. Methods In this prospective study, 22 bilateral NTG patients showing a unilateral ODH and 29 bilateral NTG patients without an episode of ODH were included. Eyes were categorized into group A (n = 22, eyes with ODH), group B (n = 22, fellow eyes without ODH), and group C (n = 29, NTG eyes without an episode of ODH). A contact lens ophthalmodynamometer was used to measure CRVP and central retinal arterial pressure (CRAP). Results Intraocular pressure (IOP) measured on the day of contact lens ophthalmodynamometry showed no difference among groups. However, the mean baseline IOP in group A was significantly lower than that in group C (P = .008). The CRVP in group A (29.1 ± 10.8 mmHg) was significantly lower than that in group C (40.1 ± 8.8 mmHg, P = .001), but similar to that in group B (30.5 ± 8.7 mmHg, P = .409). A similar relationship was noted for CRAP. No significant eye-associated variable for ODH was found in group A and B by conditional logistic regression analysis (all P > 0.05). However, multivariate logistic regression analysis in groups A and C revealed that low mean baseline IOP (odds ratio [OR] = 0.69, 95% confidence interval [CI] 0.49-0.98, P = 0.043) and low CRVP (OR = 0.88, 95% CI 0.80-0.95, P = 0.003) were associated with ODH. Conclusions CRVP was lower in NTG eyes with ODH than in eyes without an episode of ODH, but similar to that of fellow eyes without ODH. These imply less likelihood of association between increased central retinal venous resistance and ODH. PMID:25996599

  6. Acute retinal necrosis results in low vision in a young patient with a history of herpes simplex virus encephalitis.

    PubMed

    Shahi, Sanjeet K

    2016-08-31

    Acute retinal necrosis (ARN), secondary to herpes simplex encephalitis, is a rare syndrome that can present in healthy individuals, as well as immuno-compromised patients. Most cases are caused by a secondary infection from the herpes virus family, with varicella zoster virus being the leading cause of this syndrome. Potential symptoms include blurry vision, floaters, ocular pain and photophobia. Ocular findings may consist of severe uveitis, retinal vasculitis, retinal necrosis, papillitis and retinal detachment. Clinical manifestations of this disease may include increased intraocular pressure, optic disc oedema, optic neuropathy and sheathed retinal arterioles. A complete work up is essential to rule out cytomegalovirus retinitis, herpes simplex encephalitis, herpes virus, syphilis, posterior uveitis and other conditions. Depending on the severity of the disease, the treatment options consist of anticoagulation therapy, cycloplegia, intravenous acyclovir, systemic steroids, prophylactic laser photocoagulation and pars plana vitrectomy with silicon oil for retinal detachment. An extensive history and clinical examination is crucial in making the correct diagnosis. Also, it is very important to be aware of low vision needs and refer the patients, if expressing any sort of functional issues with completing daily living skills, especially reading. In this article, we report one case of unilateral ARN 20 years after herpetic encephalitis.

  7. Acute Retinal Ischemia Inhibits Endothelium-Dependent Nitric Oxide–Mediated Dilation of Retinal Arterioles via Enhanced Superoxide Production

    PubMed Central

    Ren, Yi; Potts, Luke B.; Yuan, Zhaoxu; Kuo, Enoch; Rosa, Robert H.; Kuo, Lih

    2012-01-01

    Purpose. Because retinal vascular disease is associated with ischemia and increased oxidative stress, the vasodilator function of retinal arterioles was examined after retinal ischemia induced by elevated intraocular pressure (IOP). The role of superoxide anions in the development of vascular dysfunction was assessed. Methods. IOP was increased and maintained at 80 to 90 mm Hg for 30, 60, or 90 minutes by infusing saline into the anterior chamber of a porcine eye. The fellow eye with normal IOP (10–20 mm Hg) served as control. In some pigs, superoxide dismutase mimetic TEMPOL (1 mM) or vehicle (saline) was injected intravitreally before IOP elevation. After enucleation, retinal arterioles were isolated and pressurized without flow for functional analysis by recording diameter changes using videomicroscopic techniques. Dihydroethidium (DHE) was used to detect superoxide production in isolated retinal arterioles. Results. Isolated retinal arterioles developed stable basal tone and the vasodilations to endothelium-dependent nitric oxide (NO)-mediated agonists bradykinin and L-lactate were significantly reduced only by 90 minutes of ischemia. However, vasodilation to endothelium-independent NO donor sodium nitroprusside was unaffected after all time periods of ischemia. DHE staining showed that 90 minutes of ischemia significantly increased superoxide levels in retinal arterioles. Intravitreal injection of membrane-permeable radical scavenger but not vehicle before ischemia prevented elevation of vascular superoxide and preserved bradykinin-induced dilation. Conclusions. Endothelium-dependent NO-mediated dilation of retinal arterioles is impaired by 90 minutes of ischemia induced by elevated IOP. The inhibitory effect appears to be mediated by the alteration of NO signaling via vascular superoxide. PMID:22110081

  8. Importance of Central Retinal Sensitivity for Prediction of Visual Acuity after Intravitreal Bevacizumb in Eyes with Macular Edema Associated with Branch Retinal Vein Occlusion

    PubMed Central

    Sugimoto, Masahiko; Ichio, Atsushi; Kondo, Mineo

    2016-01-01

    Objective To determine whether the baseline retinal sensitivity can predict the best-corrected visual acuity (BCVA) at 1 month after intravitreal bevacizumab (IVB) in eyes with macular edema (ME) associated with a branch retinal vein occlusion (BRVO). Subjects and Methods We evaluated 16 eyes of 16 patients who had ME associated with a BRVO. The mean ± standard deviation age was 69.1 ± 8.9 years, and all had a single IVB injection. The BCVA, central macular thickness (CMT), integrity of the ellipsoid zone (EZ) of the photoreceptors, and retinal sensitivity were determined before (baseline) and at 1 day, 1 week, and 1 month following the IVB. The average threshold retinal sensitivity (AT) within the central 10° was determined by Macular Integrity Assessment. The correlations between the BCVA at 1 month and the CMT, integrity of the EZ, and AT at each visit were determined. Results One month after IVB, the BCVA improved significantly from 0.56 ± 0.27 logMAR units to 0.32 ± 0.28 logMAR units, and the CMT from 611.4 ± 209.3 μm to 258.7 ± 64.0 μm (P <0.05). The AT improved significantly from 17.9 ± 5.3 dB to 21.2 ± 5.0 dB (P <0.05). At 1 day after the treatment, both the integrity of the EZ (r = 0.59) and the retinal sensitivity (r = 0.76) were moderately correlated with the BCVA at 1 month. Conclusion These results indicate that both the integrity of the EZ and the AT at 1 day after the IVB can predict the BCVA after treatment for ME associated with BRVO. There is a possibility that these parameters will predict the effectiveness of IVB for each case. PMID:26885822

  9. Central Retinal and Posterior Ciliary Artery Occlusion After Intralesional Injection of Sclerosant to Glabellar Subcutaneous Hemangioma

    SciTech Connect

    Matsuo, Toshihiko; Fujiwara, Hiroyasu; Gobara, Hideo; Mimura, Hidefumi; Kanazawa, Susumu

    2009-03-15

    The aim of this study is to describe vision loss caused by central retinal artery and posterior ciliary artery occlusion as a consequence of sclerotherapy with a polidocanol injection to a glabellar hemangioma. An 18-year-old man underwent direct injection with a 23-gauge needle of 1 mL of a polidocanol-carbon dioxide emulsion into the glabellar subcutaneous hemangioma under ultrasound visualization of the needle tip by radiologists. He developed lid swelling the next day, and 3 days later at referral, the visual acuity in the left eye was no light perception. Funduscopy revealed central retinal artery occlusion and fluorescein angiography disclosed no perfusion at all in the left fundus, indicating concurrent posterior ciliary artery occlusion. The patient also showed mydriasis, blepharoptosis, and total external ophthalmoplegia on the left side. Magnetic resonance imaging demonstrated the swollen medial rectus muscle. In a month, blepharoptosis and ophthalmoplegia resolved but the visual acuity remained no light perception. Sclerosing therapy for facial hemangioma may develop a severe complication such as permanent visual loss.

  10. Vitrectomy with complete posterior hyaloid removal for ischemic central retinal vein occlusion: Series of cases

    PubMed Central

    Leizaola-Fernández, Carlos; Suárez-Tatá, Luis; Quiroz-Mercado, Hugo; Colina-Luquez, Juner; Fromow-Guerra, J; Jiménez-Sierra, Juan M; Guerrero-Naranjo, Jose L; Morales-Cantón, Virgilio

    2005-01-01

    Background Central retinal vein occlusion (CRVO) is a common retinal vascular disorder with potentially complications: (1) persistent macular edema and (2) neovascular glaucoma. No safe treatment exists that promotes the return of lost vision. Eyes with CRVO may be predisposed to vitreous degeneration. It has been suggested that if the vitreous remains attached to the macula owing to a firm vitreomacular adhesion, the resultant vitreous traction can cause inflammation with retinal capillary dilation, leakage and subsequent edema6. The roll of vitrectomy in ischemic CRVO surgical procedures has not been evaluated. Case presentation This is a non comparative, prospective, longitudinal, experimental and descriptive series of cases. Ten eyes with ischemic CRVO. Vitrectomy with complete posterior hyaloid removal was performed. VA, rubeosis, intraocular pressure (IOP), and macular edema were evaluated clinically. Multifocal ERG (m-ERG), fluorescein angiography (FAG) and optic coherence tomography (OCT) were performed. Follow-up was at least 6 months. Moderate improvement of visual acuity was observed in 60% eyes and stabilized in 40%. IOP changed from 15.7 ± 3.05 mmHg to 14.9 ± 2.69 mmHg post-operative and macular edema from 976 ± 196 μm to 640 ± 191 μm to six month. The P1 wave amplitude changed from 25.46 ± 12.4 mV to 20.54 ± 11.2 mV. Conclusion A solo PPV with posterior hyaloid removal may help to improve anatomic and functional retina conditions in some cases. These results should be considered when analyzing other surgical maneuvers. PMID:15943889

  11. Successful treatment of central retinal artery thromboembolism with ocular massage and intravenous acetazolamide.

    PubMed

    Duxbury, Oliver; Bhogal, Pervinder; Cloud, Geoffrey; Madigan, Jeremy

    2014-12-05

    A 67-year-old woman presented with left-sided headache and blurred vision, worse during hypertensive episodes. CT angiography showed a 4 mm left internal carotid artery (ICA) aneurysm incorporating the ophthalmic artery. She passed a test balloon occlusion, so the aneurysm was coil occluded, without immediate complication. Four days postprocedure she experienced sudden loss of vision in the left eye and funduscopy showed central retinal artery occlusion secondary to emboli from the coiled aneurysm. She was treated promptly with intravenous acetazolamide and ocular massage and regained full visual acuity. Thromboembolism to the eye during or after neurointerventional treatment is a relatively rare but devastating complication. This report demonstrates the effectiveness of combined intravenous acetazolamide and ocular massage in dealing with this complication when delivered promptly.

  12. Central retinal vein occlusion in an otherwise healthy child treated successfully with a single injection of bevacizumab.

    PubMed

    Zheng, Linda; Gillies, Mark; Martin, Frank J

    2015-10-01

    We describe the case of an otherwise healthy 13-year-old boy who presented with blurred vision and deteriorating visual acuity in his left eye. Fundus examination showed left optic disk swelling, exudates, and hemorrhages. He was found to have an elevated left central retinal venous pressure to the level of arterial diastolic pressure, an elevated left central macular thickness and a prolonged disk-to-disk transit time on fluorescein angiography, which confirmed the diagnosis of unilateral central retinal vein occlusion (CRVO). The child was treated with one injection of bevacizumab. He has maintained visual acuity of 6/6 for 2 years following treatment, despite persistent elevated left central venous pressure and chronic optic disk edema.

  13. Retinal Disorders

    MedlinePlus

    ... be serious enough to cause blindness. Examples are Macular degeneration - a disease that destroys your sharp, central vision Diabetic eye disease Retinal detachment - a medical emergency, when the retina is ... children. Macular pucker - scar tissue on the macula Macular hole - ...

  14. Potential anti-vascular endothelial growth factor therapies for central retinal vein occlusion.

    PubMed

    Figueroa, Marta S; Contreras, Inés

    2012-11-12

    Central retinal vein occlusion (CRVO) remains an important cause of visual loss. Impaired venous drainage leads to retinal hypoxia with upregulation and release of vascular endothelial growth factor (VEGF). VEGF increases vascular permeability and leads to the breakdown of the blood-retinal barrier, with the development of macular oedema. Treatment strategies for macular oedema in CRVO currently under evaluation focus on VEGF blockage. Bevacizumab is a humanized monoclonal antibody that blocks VEGF. It has been evaluated in a clinical trial that compared intravitreal injections of bevacizumab 1.25 mg with sham injections every 6 weeks. At the end of a 24-week follow-up period, 60.0% of patients in the bevacizumab group had gained ≥ 15 letters compared with 20.0% in the control group (p=0.003). Aflibercept (previously VEGF Trap-Eye) is a 115  kD decoy receptor fusion protein. Aflibercept is capable of binding both VEGF and placental growth factor (PlGF). By blocking both VEGF and PlGF, aflibercept could be more effective than other anti-VEGF drugs. Two clinical trials have evaluated the efficacy of aflibercept for the treatment of macular oedema in CRVO: COPERNICUS and GALILEO. Both included a similar 6-month phase, during which patients were randomized to receive either an intravitreal injection of aflibercept 2 mg or a sham injection every month. In a second 6-month phase of the GALILEO study, patients in the treatment group were treated on an as needed (PRN) basis with aflibercept, while patients in the placebo group continued with sham injections. In the second 6-month phase in the COPERNICUS study, all patients were treated with aflibercept on a PRN basis. Treatment with aflibercept led to an improvement in visual acuity of ≥ 15 letters in 55.3% (COPERNICUS) and 60.2% of patients (GALILEO). Patients initially in the placebo group and then treated PRN gained only a mean of 3.8 letters, with 30.1% achieving a visual gain of ≥ 15 letters (COPERNICUS). The

  15. Optical coherence tomography angiography microvascular findings in macular edema due to central and branch retinal vein occlusions

    PubMed Central

    Rodolfo, Mastropasqua; Lisa, Toto; Luca, Di Antonio; Enrico, Borrelli; Alfonso, Senatore; Marta, Di Nicola; Giuseppe, Di Martino; Marco, Ciancaglini; Carpineto, Paolo

    2017-01-01

    The aim of this study was to evaluate retinal and choriocapillaris vessel density using optical coherence tomography angiography (OCTA) in eyes with central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO) complicated by macular edema (ME). Sixty eyes of 60 patients with CRVO or BRVO and ME and 40 healthy subjects underwent measurements of superficial and deep foveal and parafoveal vessel density (FVD, PFVD) and choricapillary density using OCTA at baseline and 60 days after intravitreal dexamethasone implant (IVDEX). FVD and PFVD of the superficial plexus were not significantly lower in CRVO group compared to the controls while in the BRVO group overall PFVD were significantly lower compared to control group (p < 0.001). Overall PFVD of the deep plexus was significantly lower in CRVO and BRVO groups compared to the control group (p < 0.001). FVD and overall PFVD of choriocapillaris were significantly reduced compared to controls in CRVO group (p < 0.001) and PFVD of choriocapillaris was significantly reduced compared to controls in the affected hemi fields in BRVO groups (p < 0.001). OCTA showed vessel density reduction in BRVO and CRVO with main involvement of the deep retinal plexus compared to the superficial retinal plexus due to ischemia that did not recover after intravitreal dexamethasone implant. PMID:28098203

  16. Acute retinal necrosis (ARN) in the context of neonatal HSV-2 exposure and subconjunctival dexamethasone: case report and literature review.

    PubMed

    McGrath, Lindsay; Woods, Marion; Lee, Lawrence; Conrad, Diana

    2013-01-01

    HSV-2 is an important cause of the acute retinal necrosis (ARN) syndrome in younger patients. We describe an atypical case of HSV-2 ARN in the context of neonatal exposure and subconjunctival steroid injection. Clinicians should be aware of the association of neonatal or congenital exposure to HSV-2 as a risk factor for this disease because early treatment may improve outcome and/or avoid involvement of both eyes.

  17. Assessing the Relationship between Central Corneal Thickness and Retinal Nerve Fiber Layer Thickness in Healthy Subjects

    PubMed Central

    Mumcuoglu, Tarkan; Townsend, Kelly A; Wollstein, Gadi; Ishikawa, Hiroshi; Bilonick, Richard A; Sung, Kyung Rim; Kagemann, Larry; Schuman, Joel S

    2008-01-01

    Purpose To determine the relationship between central corneal thickness (CCT) and retinal nerve fiber layer (RNFL) thickness obtained by scanning laser polarimetry (GDx-VCC; Carl Zeiss Meditec, Dublin, CA) confocal scanning laser ophthalmoscopy (HRT II; Heidelberg Engineering, Heidelberg, Germany) and optical coherence tomography (Stratus OCT; Carl Zeiss Meditec, Dublin, CA). Design Multi-center clinical trial, retrospective cross-sectional study. Methods One hundred and nine healthy subjects from the Advanced Imaging in Glaucoma Study were enrolled in this study. All subjects had a standard clinical examination, including visual field and good quality scans from all three imaging devices. Central corneal thickness was measured using an ultrasonic pachymeter. A linear mixed effects model was used to assess the relationship between RNFL thickness and CCT, accounting for clustering of eyes within subjects, testing site, ethnicity, family history of glaucoma, axial length intraocular pressure and visual field global indices. Results For OCT and GDx, there was a slight non-statistically significant positive relationship between CCT and RNFL thickness. For HRT, there was a slight non-statistically significant negative relationship between CCT and RNFL thickness. Relationships for each device were found to differ between sites. Conclusions CCT was not statistically significantly related to RNFL thickness in healthy eyes. PMID:18657796

  18. Arterial blood flow characteristics in central retinal vein occlusion and effects of panretinal photocoagulation treatment: an investigation by colour Doppler imaging

    PubMed Central

    Avunduk, A. M.; Dinc, H.; Kapicioglu, Z.; Ugurlu, S.; Dayanir, V.; Korkmaz, E.

    1999-01-01

    AIMS—To determine whether an increase in vascular resistance in the central retinal and ophthalmic arterial circulations contributes to the development of central retinal vein occlusion (CRVO), or haemodynamic alterations in central retinal and ophthalmic arteries occur secondary to the vein occlusion as increased intravascular pressure is transferred through the capillary bed to the arterial side and the effect of panretinal photocoagulation treatment on these circulations in ischaemic cases.
METHODS—The ophthalmic and central retinal arteries of the affected and non-affected eyes of 20 patients with non-ischaemic CRVO, 13 patients with ischaemic CRVO, and 22 control subjects were investigated by colour Doppler imaging. Panretinal photocoagulation (PRP) treatment was applied to the eyes with ischaemic CRVO. Maximum and minimum blood flow velocities, and resistivity indexes were calculated in the affected and healthy eyes of patients and in the control eyes.
RESULTS—Average blood flow velocity in the central retinal and ophthalmic arteries of patients with non-ischaemic CRVO did not differ from their fellow eyes, but a significantly lower average blood flow velocity was found in the ophthalmic and central retinal arteries of the patients with ischaemic CRVO compared with their fellow eyes. Patients with ischaemic CRVO had significantly lower blood flow velocities in their ophthalmic and central retinal arteries than non-ischaemic cases that were further reduced following PRP treatment.
CONCLUSION—This study suggests that impaired arterial blood flow observed in patients with CRVO may be partly related to secondary changes in the retrobulbar arterial circulation as a result of enhanced arterial resistance following CRVO. These data also demonstrate that PRP treatment decreases retinal and ophthalmic blood flow velocities in patients with ischaemic CRVO.

 Keywords: central retinal vein occlusion; panretinal photocoagulation; arterial circulation

  19. Central diabetes insipidus in children with acute brain insult.

    PubMed

    Yang, Yun-Hsuan; Lin, Jainn-Jim; Hsia, Shao-Hsuan; Wu, Chang-Teng; Wang, Huei-Shyong; Hung, Po-Cheng; Chou, Min-Liang; Hsieh, Meng-Ying; Lin, Kuang-Lin

    2011-12-01

    Central diabetes insipidus occurs in patients with overwhelming central nervous system injuries, and may be associated with brain death. The clinical picture of children with acquired central diabetes insipidus after acute brain insult is seldom reported. We retrospectively reviewed cases dating from January 2000-February 2008 at a tertiary pediatric intensive care unit. Fifty-four patients (28 girls, 26 boys), aged 3 months to 18 years, were enrolled. Etiologies included severe central nervous system infection (35.2%), hypoxic-ischemic events (31.5%), head injury (18.5%), and vascular lesions (14.8%). In 39 (72.2%) patients, diabetes insipidus was diagnosed during the first 2 days after acute central nervous system injury, and 40 (74.0%) developed maximum serum sodium concentrations of >160 mEq/L. In 16, sequential cerebral salt wasting syndrome developed after their initial diabetes insipidus presentation. Overall mortality at 2 months after admission was 77.8%. Our results demonstrate that patients who develop central diabetes insipidus after acute central nervous system injury manifest high mortality. Development of central diabetes insipidus within the first 2 days and a maximum plasma sodium >160 mEq/L were significant predictors of outcomes.

  20. Anti-vascular endothelial growth factor for macular oedema secondary to central retinal vein occlusion

    PubMed Central

    Braithwaite, Tasanee; Nanji, Afshan A; Lindsley, Kristina; Greenberg, Paul B

    2014-01-01

    Background Central retinal vein occlusion (CRVO) is a relatively common retinal vascular disorder in which macular oedema may develop, with a consequent reduction in visual acuity. Until recently there has been no treatment of proven benefit, but growing evidence supports the use of anti-vascular endothelial growth factor (anti-VEGF) agents. Objectives To investigate the effectiveness and safety of anti-VEGF therapies for the treatment of macular oedema secondary to CRVO. Search methods We searched CENTRAL (which contains the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 10), Ovid MEDLINE (January 1950 to October 2013), EMBASE (January 1980 to October 2013), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to October 2013), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (January 1937 to October 2013), OpenGrey, OpenSIGLE (January 1950 to October 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), Clinical-Trials.gov (www.clinicaltrials.gov), the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en) and Web of Science Conference Proceedings Citation Index-Science (CPCI-S). There were no language or date restrictions in the electronic search for trials. The electronic databases and clinical trials registers were last searched on 29th October 2013. Selection criteria We considered randomised controlled trials (RCTs) that compared intravitreal anti-VEGF agents of any dose or duration to sham injection or no treatment. We focused on studies that included individuals of any age or gender and a minimum of six months follow-up. Data collection and analysis Two review authors independently assessed trial quality and extracted data. The primary outcome was the proportion of participants with a gain in best-corrected visual acuity (BCVA) from baseline of

  1. Acute retinal necrosis in the United Kingdom: results of a prospective surveillance study

    PubMed Central

    Cochrane, T F; Silvestri, G; McDowell, C; Foot, B; McAvoy, C E

    2012-01-01

    Background To determine the incidence of acute retinal necrosis (ARN) in the United Kingdom and to describe the demographics, management, and visual outcome in these patients. Methods This was a prospective study carried out by the British Ophthalmological Surveillance Unit (BOSU) between September 2007 and October 2008. Initial and 6-month questionnaires were sent to UK ophthalmologists who reported cases of ARN via the monthly BOSU report card system. Results In all, 45 confirmed cases (52 eyes) of ARN were reported in the 14-month study period, giving a minimum incidence of 0.63 cases per million population per year. There were 20 females and 25 males. Age ranged from 10 to 94 years. Eight patients had a history of herpetic CNS disease. Aqueous sampling was carried out in 13 patients, vitreous in 27, and cerebrospinal fluid (CSF) in 4. Varicella-zoster virus followed by herpes simplex were the most common causative agents. Treatment in 76% of the cases was with intravenous antivirals; however, 24% received only oral antivirals. In all, 47% of patients had intravitreal antiviral therapy. Visual outcome at 6 months was <6/60 in 48% of the affected eyes. Conclusion The minimum incidence of ARN in the UK is 0.63 cases per million. Patients with a history of herpetic CNS disease should be warned to immediately report any visual symptoms. There is increased use of oral and intravitreal antivirals in initial treatment. PMID:22281865

  2. The Relationship of Central Foveal Thickness to Urinary Iodine Concentration in Retinitis Pigmentosa Patients with or without Cystoid Macular Edema

    PubMed Central

    Sandberg, Michael A.; Pearce, Elizabeth N.; Harper, Shyana; Weigel-DiFranco, Carol; Hart, Lois; Rosner, Bernard; Berson, Eliot L.

    2014-01-01

    Importance Current treatments for cystoid macular edema in retinitis pigmentosa are not always effective, may lead to adverse side effects, and may not restore loss of visual acuity. The present research lays the rationale for evaluating whether an iodine supplement could reduce cystoid macular edema in retinitis pigmentosa. Objective To determine whether central foveal thickness in the presence of cystoid macular edema is related to dietary iodine intake inferred from urinary iodine concentration in non-smoking adults with retinitis pigmentosa. Design Cross-sectional study. Setting Institutional referral center. Participants Non-smoking adult patients with retinitis pigmentosa (n = 212, ages 18 to 69 years) with a visual acuity ≥ 20/200 in at least one eye. Main outcome measure The relationship of log central foveal thickness measured by optical coherence tomography to urinary iodine concentration measured from multiple spot samples and represented as a 3-level classification variable (< 100 μg/L, 100 μg/L - 199 μg/L, and ≥ 200 μg/L), assigning greater weight to patients with more reliable urinary iodine concentration estimates. Results Analyses were limited to 199 patients after excluding 11 patients who failed to return urine samples for measuring urinary iodine concentration and 2 outliers for urinary iodine concentration. Thirty-six percent of these patients had cystoid macular edema in one or both eyes. Although log central foveal thickness was inversely related to urinary iodine concentration based on all patients (p = 0.02), regression of log central foveal thickness on urinary iodine concentration separately for patients with and without cystoid macular edema showed a strong inverse significant relationship for the former group (p < 0.001) and no significant relationship for the latter group as tested (p = 0.66). In contrast, we found no significant association between cystoid macular edema prevalence and urinary iodine concentration based on the

  3. Central retinal artery occlusion following laser treatment for ocular ischemic aortic arch syndrome

    PubMed Central

    Shah, Payal J.; Ellis, Brian; DiGiovine, Lauren R.; Hogg, Jeffery P.; Leys, Monique J.

    2015-01-01

    Objective: Ocular ischemic syndrome is a rare blinding condition generally caused by disease of the carotid artery. We describe a 69-year-old female with a 50 pack-year smoking history with aortic arch syndrome causing bilateral ocular ischemic syndrome. Methods: The patient presented with progressive visual loss and temple pain. Slit lamp biomicroscopy revealed bilateral iris neovascularization. This finding prompted a cardiovascular work up. Panretinal photocoagulation with retrobulbar block was performed in the right eye. Results: A temporal artery biopsy was negative. The carotid duplex ultrasound showed only a 1–39% stenosis. MRA revealed a more proximal occlusion of the aortic branch for which she underwent subclavian carotid bypass surgery. At the one month follow up, the right eye suffered profound vision loss secondary to a central retinal artery occlusion. Conclusion: Ocular neovascularization may be one of the clinical manifestations of aortic arch syndrome. This case also illustrates the limitations of relying solely on carotid duplex ultrasound testing. We caution against overly aggressive panretinal photocoagulation utilizing retrobulbar anesthesia. PMID:27625958

  4. Selective thrombolysis performed through meningo-ophthalmic artery in central retinal artery occlusion.

    PubMed

    Cohen, José E; Moscovici, Samuel; Halpert, Michael; Itshayek, Eyal

    2012-03-01

    The poor natural history of central retinal artery occlusion (CRAO) is usually not modified with conventional, conservative management techniques. Guidelines for selective intraarterial ophthalmic thrombolysis are still lacking. While many centers continue to perform this procedure with promising results, others are reluctant due to conflicting findings in recent studies. We present our experience in a 36-year-old male with CRAO. Based on the patient's clinical presentation, we planned to perform selective intraarterial ophthalmic thrombolysis via the ophthalmic artery. When angiography demonstrated that the retina was not supplied by the ophthalmic artery, but by a meningo-ophthalmic artery branching from the internal maxillary artery, we instead administered thrombolytic agents via the meningo-ophthalmic artery. The patient's vision recovered completely, with visual acuity and visual field examination at 30 day follow up comparable to his pre-treatment status. This case emphasizes the need for external carotid artery examination in cases of nonvisualization of the ophthalmic artery. In addition, it illustrates the successful use of the meningo-ophthalmic artery to perform selective intraarterial thrombolysis for CRAO.

  5. Risk factors for central and branch retinal vein occlusion: a meta-analysis of published clinical data.

    PubMed

    Kolar, Petr

    2014-01-01

    Retinal vein occlusion (RVO) is a major cause of vision loss. Of the two main types of RVO, branch retinal vein occlusion (BRVO) is 4 to 6 times more prevalent than central retinal vein occlusion (CRVO). A basic risk factor for RVO is advancing age. Further risk factors include systemic conditions like hypertension, arteriosclerosis, diabetes mellitus, hyperlipidemia, vascular cerebral stroke, blood hyperviscosity, and thrombophilia. A strong risk factor for RVO is the metabolic syndrome (hypertension, diabetes mellitus, and hyperlipidemia). Individuals with end-organ damage caused by diabetes mellitus and hypertension have greatly increased risk for RVO. Socioeconomic status seems to be a risk factor too. American blacks are more often diagnosed with RVO than non-Hispanic whites. Females are, according to some studies, at lower risk than men. The role of thrombophilic risk factors in RVO is still controversial. Congenital thrombophilic diseases like factor V Leiden mutation, hyperhomocysteinemia and anticardiolipin antibodies increase the risk of RVO. Cigarette smoking also increases the risk of RVO as do systemic inflammatory conditions like vasculitis and Behcet disease. Ophthalmic risk factors for RVO are ocular hypertension and glaucoma, higher ocular perfusion pressure, and changes in the retinal arteries.

  6. ASSESSMENT OF VISUAL FUNCTION AND RETINAL STRUCTURE FOLLOWING ACUTE LIGHT EXPOSURE IN THE LIGHT SENSITIVE T4R RHODOPSIN MUTANT DOG

    PubMed Central

    Iwabe, Simone; Ying, Gui-Shuang; Aguirre, Gustavo D.; Beltran, William A.

    2016-01-01

    severe damage at 36 weeks post LE in all four meridians. The RHOT4R/T4R retina exposed to the high dose showed at 2 weeks after LE extensive ONL damage in all four meridians. This light intensity did not cause any retinal damage in WT dogs even after repeated (up to 3) LE. Analysis of ONL thickness in heterozygous mutant dogs exposed to the moderate dose of light confirmed the increased sensitivity to light damage of the superior/tapetal retina, and the occurrence of an ongoing cell death process several weeks after the acute LE. In conclusion, a short single exposure to a dose of white light that is not retinotoxic in WT dogs causes in the T4R RHO retina an acute loss of ONL in the central to mid peripheral region that keeps progressing over the course of several weeks. However, this severe retinal damage does not affect visual behavior presumably because of islands of surviving photoreceptors found in the area centralis including the newly discovered canine fovea-like area, and the lack of damage to peripheral photoreceptors. PMID:27085210

  7. Concise Review: Dental Pulp Stem Cells: A Novel Cell Therapy for Retinal and Central Nervous System Repair.

    PubMed

    Mead, Ben; Logan, Ann; Berry, Martin; Leadbeater, Wendy; Scheven, Ben A

    2017-01-01

    Dental pulp stem cells (DPSC) are neural crest-derived ecto-mesenchymal stem cells that can relatively easily and non-invasively be isolated from the dental pulp of extracted postnatal and adult teeth. Accumulating evidence suggests that DPSC have great promise as a cellular therapy for central nervous system (CNS) and retinal injury and disease. The mode of action by which DPSC confer therapeutic benefit may comprise multiple pathways, in particular, paracrine-mediated processes which involve a wide array of secreted trophic factors and is increasingly regarded as the principal predominant mechanism. In this concise review, we present the current evidence for the use of DPSC to repair CNS damage, including recent findings on retinal ganglion cell neuroprotection and regeneration in optic nerve injury and glaucoma. Stem Cells 2017;35:61-67.

  8. Acute Psychosis as Main Manifestation of Central Pontine Myelinolysis

    PubMed Central

    Gopal, Mangala; Patel, Harsh

    2017-01-01

    Central pontine myelinolysis (CPM) is an acute demyelinating neurological disorder affecting primarily the central pons and is frequently associated with rapid correction of hyponatremia. Common clinical manifestations of CPM include spastic quadriparesis, dysarthria, pseudobulbar palsy, and encephalopathy of various degrees; however, coma, “locked-in” syndrome, or death can occur in most severe cases. Rarely, CPM presents with neuropsychiatric manifestations, such as personality changes, acute psychosis, paranoia, hallucinations, or catatonia, typically associated with additional injury to the brain, described as extrapontine myelinolysis (EPM). We present a patient with primarily neuropsychiatric manifestations of CPM, in the absence of focal neurologic deficits or radiographic extrapontine involvement. A 51-year-old female without significant medical history presented with dizziness, frequent falls, diarrhea, generalized weakness, and weight loss. Physical examination showed no focal neurological deficits. Laboratory data showed severe hyponatremia, which was corrected rather rapidly. Subsequently, the patient developed symptoms of an acute psychotic illness. Initial brain magnetic resonance imaging (MRI) was unremarkable, although a repeat MRI two weeks later revealed changes compatible with CPM. This case demonstrates that acute psychosis might represent the main manifestation of CPM, especially in early stages of the disease, which should be taken into consideration when assessing patients with acute abnormalities of sodium metabolism. PMID:28392953

  9. Interventions for asymptomatic retinal breaks and lattice degeneration for preventing retinal detachment

    PubMed Central

    Wilkinson, Charles P

    2016-01-01

    Background Asymptomatic retinal breaks and lattice degeneration are visible lesions that are risk factors for later retinal detachment. Retinal detachments occur when fluid in the vitreous cavity passes through tears or holes in the retina and separates the retina from the underlying retinal pigment epithelium. Creation of an adhesion surrounding retinal breaks and lattice degeneration, with laser photocoagulation or cryotherapy, has been recommended as an effective means of preventing retinal detachment. This therapy is of value in the management of retinal tears associated with the symptoms of flashes and floaters and persistent vitreous traction upon the retina in the region of the retinal break, because such symptomatic retinal tears are associated with a high rate of progression to retinal detachment. Retinal tears and holes unassociated with acute symptoms and lattice degeneration are significantly less likely to be the sites of retinal breaks that are responsible for later retinal detachment. Nevertheless, treatment of these problems is frequently recommended, in spite of the fact that the effectiveness of this therapy is unproven. Objectives The purpose of this review was to evaluate the effectiveness of interventions for asymptomatic retinal breaks and lattice degeneration. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 1), MEDLINE (January 1950 to January 2012), EMBASE (January 1980 to January 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 28 January 2012. Textbooks regarding retinal detachment and the reference lists of relevant reports were reviewed for additional

  10. Macular Cone Abnormalities in Retinitis Pigmentosa with Preserved Central Vision Using Adaptive Optics Scanning Laser Ophthalmoscopy

    PubMed Central

    Makiyama, Yukiko; Ooto, Sotaro; Hangai, Masanori; Takayama, Kohei; Uji, Akihito; Oishi, Akio; Ogino, Ken; Nakagawa, Satoko; Yoshimura, Nagahisa

    2013-01-01

    Purpose To assess macular photoreceptor abnormalities in eyes with retinitis pigmentosa (RP) with preserved central vision using adaptive optics scanning laser ophthalmoscopy (AO-SLO). Methods Fourteen eyes of 14 patients with RP (best-corrected visual acuity 20/20 or better) and 12 eyes of 12 volunteers underwent a full ophthalmologic examination, fundus autofluorescence, spectral-domain optical coherence tomography (SD-OCT), and imaging with a prototype AO-SLO system. Cone density and spatial organization of the cone mosaic were assessed using AO-SLO images. Results In 3 eyes with RP and preserved central vision, cones formed a mostly regular mosaic pattern with small patchy dark areas, and in 10 eyes, the cone mosaic patterns were less regular, and large dark regions with missing cones were apparent. Only one eye with RP demonstrated a normal, regular cone mosaic pattern. In eyes with RP, cone density was significantly lower at 0.5 mm and 1.0 mm from the center of the fovea compared to normal eyes (P<0.001 and 0.021, respectively). At 0.5 mm and 1.0 mm from the center of the fovea, a decreased number of cones had 6 neighbors in eyes with RP (P = 0.002 for both). Greater decrease in cone density was related to disruption of the photoreceptor inner segment (IS) ellipsoid band on SD-OCT images (P = 0.044); however, dark regions were seen on AO-SLO even in areas of continuous IS ellipsoid on SD-OCT. Decreased cone density correlated thinner outer nuclear layer (P = 0.029) and thinner inner segment and outer segment thickness (P = 0.011) on SD-OCT. Conclusions Cone density is decreased and the regularity of the cone mosaic spatial arrangement is disrupted in eyes with RP, even when visual acuity and foveal sensitivity are good. AO-SLO imaging is a sensitive quantitative tool for detecting photoreceptor abnormalities in eyes with RP. PMID:24260224

  11. Changes in central retinal artery blood flow after ocular warming and cooling in healthy subjects

    PubMed Central

    Shamshad, M A; Amitava, A K; Ahmad, I; Wahab, S

    2010-01-01

    Context: Retinal perfusion variability impacts ocular disease and physiology. Aim: To evaluate the response of central retinal artery (CRA) blood flow to temperature alterations in 20 healthy volunteers. Setting and Design: Non-interventional experimental human study. Materials and Methods: Baseline data recorded: Ocular surface temperature (OST) in °C (thermo-anemometer), CRA peak systolic velocity (PSV) and end diastolic velocity (EDV) in cm/s using Color Doppler. Ocular laterality and temperature alteration (warming by electric lamp/cooling by ice-gel pack) were randomly assigned. Primary outcomes recorded were: OST and intraocular pressure (IOP) immediately after warming or cooling and ten minutes later; CRA-PSV and EDV at three, six and nine minutes warming or cooling. Statistical Analysis: Repeated measures ANOVA. Results: (n = 20; μ ± SD): Pre-warming values were; OST: 34.5 ± 1.02°C, CRA-PSV: 9.3 ± 2.33 cm/s, CRA-EDV: 4.6 ± 1.27 cm/s. OST significantly increased by 1.96°C (95% CI: 1.54 to 2.37) after warming, but returned to baseline ten minutes later. Only at three minutes, the PSV significantly rose by 1.21 cm/s (95% CI: 0.51to1.91). Pre-cooling values were: OST: 34.5 ± 0.96°C, CRA-PSV: 9.7 ± 2.45 cm/s, CRA-EDV: 4.7 ± 1.12 cm/s. OST significantly decreased by 2.81°C (95% CI: −2.30 to −3.37) after cooling, and returned to baseline at ten minutes. There was a significant drop in CRA-PSV by 1.10cm/s (95% CI: −2.05 to −0.15) and CRA-EDV by 0.81 (95% CI: −1.47 to −0.14) at three minutes. At six minutes both PSV (95% CI: −1.38 to −0.03) and EDV (95% CI: −1.26 to −0.02) were significantly lower. All values at ten minutes were comparable to baseline. The IOP showed insignificant alteration on warming (95% CI of difference: −0.17 to 1.57mmHg), but was significantly lower after cooling (95% CI: −2.95 to −4.30mmHg). After ten minutes, IOP had returned to baseline. Conclusion: This study confirms that CRA flow significantly

  12. Retinitis Pigmentosa

    MedlinePlus

    ... Action You are here Home › Retinal Diseases Listen Retinitis Pigmentosa What is retinitis pigmentosa? What are the symptoms? ... is available? What treatment is available? What is retinitis pigmentosa? Retinitis pigmentosa, also known as RP, refers to ...

  13. Inducible ablation of melanopsin-expressing retinal ganglion cells reveals their central role in non-image forming visual responses.

    PubMed

    Hatori, Megumi; Le, Hiep; Vollmers, Christopher; Keding, Sheena Racheal; Tanaka, Nobushige; Buch, Thorsten; Waisman, Ari; Schmedt, Christian; Jegla, Timothy; Panda, Satchidananda

    2008-06-11

    Rod/cone photoreceptors of the outer retina and the melanopsin-expressing retinal ganglion cells (mRGCs) of the inner retina mediate non-image forming visual responses including entrainment of the circadian clock to the ambient light, the pupillary light reflex (PLR), and light modulation of activity. Targeted deletion of the melanopsin gene attenuates these adaptive responses with no apparent change in the development and morphology of the mRGCs. Comprehensive identification of mRGCs and knowledge of their specific roles in image-forming and non-image forming photoresponses are currently lacking. We used a Cre-dependent GFP expression strategy in mice to genetically label the mRGCs. This revealed that only a subset of mRGCs express enough immunocytochemically detectable levels of melanopsin. We also used a Cre-inducible diphtheria toxin receptor (iDTR) expression approach to express the DTR in mRGCs. mRGCs develop normally, but can be acutely ablated upon diphtheria toxin administration. The mRGC-ablated mice exhibited normal outer retinal function. However, they completely lacked non-image forming visual responses such as circadian photoentrainment, light modulation of activity, and PLR. These results point to the mRGCs as the site of functional integration of the rod/cone and melanopsin phototransduction pathways and as the primary anatomical site for the divergence of image-forming and non-image forming photoresponses in mammals.

  14. Infiltration of central nervous system in adult acute myeloid leukaemia.

    PubMed Central

    Pippard, M J; Callender, S T; Sheldon, P W

    1979-01-01

    Out of 64 consecutive unselected patients with acute myeloid leukaemia studied during 1973-6, five developed clinical evidence of spread to the central nervous system (CNS). Neuroradiological examination showed cerebral deposits in three, in whom rapid symptomatic relief was obtained with radiotherapy. In two of these patients who developed solid intracranial deposits haematological remission could be reinduced or maintained; they were still alive 86 and 134 weeks later. When patients presented with spread to the CNS complicating generalised uncontrolled leukaemia they had short survivals. CNS infiltration may respond dramatically to appropriate treatment provided that it is not associated with generalised uncontrolled leukaemia, which has a poor prognosis. In view of this, routine "prophylaxis" of the CNS in adult acute myeloid leukaemia does not seem justified at present. Images FIG 1 FIG 2 FIG 3 PMID:283873

  15. The Relationship between OCT-measured Central Retinal Thickness and Visual Acuity in Diabetic Macular Edema

    PubMed Central

    2008-01-01

    Objective To compare optical coherence tomography (OCT)-measured retinal thickness and visual acuity in eyes with diabetic macular edema (DME) both before and after macular laser photocoagulation. Design Cross-sectional and longitudinal study. Participants 210 subjects (251 eyes) with DME enrolled in a randomized clinical trial of laser techniques. Methods Retinal thickness was measured with OCT and visual acuity was measured with the electronic-ETDRS procedure. Main Outcome Measures OCT-measured center point thickness and visual acuity Results The correlation coefficients for visual acuity versus OCT center point thickness were 0.52 at baseline and 0.49, 0.36, and 0.38 at 3.5, 8, and 12 months post-laser photocoagulation. The slope of the best fit line to the baseline data was approximately 4.4 letters (95% C.I.: 3.5, 5.3) better visual acuity for every 100 microns decrease in center point thickness at baseline with no important difference at follow-up visits. Approximately one-third of the variation in visual acuity could be predicted by a linear regression model that incorporated OCT center point thickness, age, hemoglobin A1C, and severity of fluorescein leakage in the center and inner subfields. The correlation between change in visual acuity and change in OCT center point thickening 3.5 months after laser treatment was 0.44 with no important difference at the other follow-up times. A subset of eyes showed paradoxical improvements in visual acuity with increased center point thickening (7–17% at the three time points) or paradoxical worsening of visual acuity with a decrease in center point thickening (18%–26% at the three time points). Conclusions There is modest correlation between OCT-measured center point thickness and visual acuity, and modest correlation of changes in retinal thickening and visual acuity following focal laser treatment for DME. However, a wide range of visual acuity may be observed for a given degree of retinal edema and paradoxical

  16. Quantification of the outer retinal layers: correlation to visual acuity in healthy subjects and patients with central serous chorioretinopathy

    NASA Astrophysics Data System (ADS)

    Sander, Birgit; Christensen, Ulrik; Larsen, Michael; Jørgensen, Thomas M.

    2007-07-01

    Purpose: Quantification of outer retinal layers in humans. Method: 11 eyes in healthy subjects and 3 eyes in patients after resolution of central serous chorioretinopathy (CSCR). Multiple line scans were obtained using OCT Stratus and scans were registered and averaged to enhance contrast. The distance from the inner-outer segment junction to the posterior part of the retinal pigment epithelium (RPE-OS complex) was calculated. In addition, the reflectance of the outer photoreceptor layer in the foveal center was compared to that peripheral to the fovea. Results: Mean thickness of the RPE-OS complex in healthy subjects was 77.3 μm, in CSCR 52.9 μm. The thickness of the RPE-OS complex was significantly correlated to visual acuity (r=0.95, p<0.01). The ratio of reflectance (fovea/parafovea) was 1.06 in healthy subjects, 1.18 in CSCR eyes. Conclusion: The RPE-OS complex thickness was markedly reduced in eyes after resolution of CSCR and highly correlated to the visual acuity, the correlation to total foveal thickness was less. An increased backscatter was seen in CSCR, probably due to photoreceptor disorganization and atrophy.

  17. An Unusual Case of Central Retinal Vein Occlusion and Review of the Toxicity Profile of Regorafenib in GIST Patients.

    PubMed

    Schvartsman, Gustavo; Wagner, Michael J; Zobniw, Chrystia M; Trinh, Van Anh; Patel, Shreyaskumar; Somaiah, Neeta

    2016-08-01

    Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the gastrointestinal tract with around 5000 new cases per year. Outcomes for patients with GIST dramatically improved after the development of tyrosine kinase inhibitors targeted against the aberrant signaling pathways that drive GIST oncogenesis. Majority of patients derive benefit from first-line imatinib, and the type of driver mutation is predictive of response. However, almost half of the patients eventually develop resistance to initial targeted therapy and further lines of treatment do not have the same impact. Regorafenib is an oral multi-kinase inhibitor approved as a third-line therapy for advanced GIST and though its efficacy is limited in comparison to imatinib, it has activity across the various driver mutation categories in GIST even in the setting of imatinib resistance. Herein, we describe a case of central retinal vein occlusion (CRVO) secondary to regorafenib and review regorafenib's efficacy and toxicity profile.

  18. Neuroprotective and antiapoptotic activity of lineage-negative bone marrow cells after intravitreal injection in a mouse model of acute retinal injury.

    PubMed

    Machalińska, Anna; Rogińska, Dorota; Pius-Sadowska, Ewa; Kawa, Miłosz P; Paczkowska, Edyta; Rudnicki, Michał; Lejkowska, Renata; Baumert, Bartłomiej; Wiszniewska, Barbara; Machaliński, Bogusław

    2015-01-01

    We investigated effects of bone marrow-derived, lineage-negative cell (Lin(-)BMC) transplantation in acute retinal injury. Lin(-)BMCs were intravitreally injected into murine eyes at 24 h after NaIO3-induced injury. Morphology, function, and expression of apoptosis-related genes, including brain-derived neurotrophic factor (BDNF) and its receptor, were assessed in retinas at 7 days, 28 days, and 3 months after transplantation. Moreover, global gene expression at day 7 was analyzed by RNA arrays. We observed that Lin(-)BMCs integrated into outer retinal layers improving morphological retinal structure and induced molecular changes such as downregulation of proapoptotic caspase-3 gene, a decrease in BAX/BCL-2 gene ratio, and significant elevation of BDNF expression. Furthermore, transplanted Lin(-)BMCs differentiated locally into cells with a macrophage-like phenotype. Finally, Lin(-)BMCs treatment was associated with generation of two distinct transcriptomic patterns. The first relates to downregulated genes associated with regulation of neuron cell death and apoptosis, response to oxidative stress/hypoxia and external stimuli, and negative regulation of cell proliferation. The second relates to upregulated genes associated with neurological system processes and sensory perception. Collectively, our data demonstrate that transplanted Lin(-)BMCs exert neuroprotective function against acute retinal injury and this effect may be associated with their antiapoptotic properties and ability to express neurotrophic factors.

  19. Neuroprotective and Antiapoptotic Activity of Lineage-Negative Bone Marrow Cells after Intravitreal Injection in a Mouse Model of Acute Retinal Injury

    PubMed Central

    Machalińska, Anna; Pius-Sadowska, Ewa; Kawa, Miłosz P.; Paczkowska, Edyta; Rudnicki, Michał; Lejkowska, Renata; Baumert, Bartłomiej; Wiszniewska, Barbara; Machaliński, Bogusław

    2015-01-01

    We investigated effects of bone marrow-derived, lineage-negative cell (Lin−BMC) transplantation in acute retinal injury. Lin−BMCs were intravitreally injected into murine eyes at 24 h after NaIO3-induced injury. Morphology, function, and expression of apoptosis-related genes, including brain-derived neurotrophic factor (BDNF) and its receptor, were assessed in retinas at 7 days, 28 days, and 3 months after transplantation. Moreover, global gene expression at day 7 was analyzed by RNA arrays. We observed that Lin−BMCs integrated into outer retinal layers improving morphological retinal structure and induced molecular changes such as downregulation of proapoptotic caspase-3 gene, a decrease in BAX/BCL-2 gene ratio, and significant elevation of BDNF expression. Furthermore, transplanted Lin−BMCs differentiated locally into cells with a macrophage-like phenotype. Finally, Lin−BMCs treatment was associated with generation of two distinct transcriptomic patterns. The first relates to downregulated genes associated with regulation of neuron cell death and apoptosis, response to oxidative stress/hypoxia and external stimuli, and negative regulation of cell proliferation. The second relates to upregulated genes associated with neurological system processes and sensory perception. Collectively, our data demonstrate that transplanted Lin−BMCs exert neuroprotective function against acute retinal injury and this effect may be associated with their antiapoptotic properties and ability to express neurotrophic factors. PMID:25810725

  20. Acute rheumatic fever outbreak in southern central European country.

    PubMed

    Kočevar, Urška; Toplak, Nataša; Kosmač, Blaž; Kopač, Luka; Vesel, Samo; Krajnc, Natalija; Homan, Matjaž; Rus, Rina; Avčin, Tadej

    2017-01-01

    A decline in the incidence of acute rheumatic fever (ARF) in developed countries over the past century can be attributed to the improved public hygiene and to widespread use of antibiotics. ARF seemed to be a rare disease in southern central European country, Slovenia, up to 2010 when we noticed an increase in the number of patients with ARF. In order to assess the current incidence of ARF, we performed a retrospective study of all patients with ARF treated at the University Children's Hospital Ljubljana from January 2008 until the end of December 2014. In a period of 7 years, 19 patients with ARF were identified. The estimated annual incidence of ARF during the study period was 1.25 cases per 100,000 children. Carditis was present in all patients, arthritis in 37 % and Sydenham chorea in 32 %.

  1. Neuropathy optic glaucomatosa induced by systemic hypertension through activation endothelin-1 signaling pathway in central retinal artery in rats

    PubMed Central

    Prayitnaningsih, Seskoati; Sujuti, Hidayat; Effendi, Maksum; Abdullah, Aulia; Anandita, Nanda Wahyu; Yohana, Febriani; Permatasari, Nur; Widodo, Mohamad Aris

    2016-01-01

    AIM To evaluate effect of hypertension on retinal ganglion cell (RGC) apoptosis, intraocular pressure (IOP), and the activation of endothelin-1 (ET-1) signaling pathway in central retinal artery (CRA) in rats. METHODS The experimental study was performed on 20 male Sprague Dawley rats that were divided into control group, and hypertension groups. The hypertension was induced by subcutaneous deoxycorticoacetate (DOCA) 10 mg/kg twice a week and administered 0.9% NaCl solution daily for 2, 6, and 10wk. Blood pressure (BP) was measured using animal BP analyzer. IOP was measured by handheld tonometry. Retinal tissue preparations by paraffin blocks were made after enucleation. The expression of ET-1, eNOS, ET-1 receptor A (ETRA), ET-1 receptor B (ETRB), and phosphorylated myosin light chain kinase (MLCK), and caldesmon (CaD) in CRA and RGC apoptosis were evaluated through immunofluorescent staining method then observed using laser scanning confocal microscopy. RESULTS BP significantly increased in all of the hypertension groups compared to control (P=0.001). Peak IOP elevation (7.78±4.14 mm Hg) and RGC apoptosis (576.15±33.28 Au) occurred on 2wk of hypertension. ET-1 expression (1238.6±55.1 Au) and eNOS expression (2814.2±70.7 Au) were found highest in 2wk of hypertension, although the ratio of ET-1/eNOS decreased since 2wk. ETRA reached peak expression in 10wk of hypertension (1219.4±6.3 Au), while ETRB significantly increased only in 2 weeks group (1069.2±9.6 Au). The highest MLCK expression (1190.09±58.32 Au), CaD (1670.28±18.36 Au) were also found in 2wk of hypertension. CONCLUSION Hypertension effects to activation of ET-1 signaling pathway significantly in CRA, elevation of IOP, and RGC apoptosis. The highest value was achieved at 2wk, which is the development phase of hypertension. PMID:27990358

  2. Retinal pathways influence temporal niche

    PubMed Central

    Doyle, Susan E.; Yoshikawa, Tomoko; Hillson, Holly; Menaker, Michael

    2008-01-01

    In mammals, light input from the retina entrains central circadian oscillators located in the suprachiasmatic nuclei (SCN). The phase of circadian activity rhythms with respect to the external light:dark cycle is reversed in diurnal and nocturnal species, although the phase of SCN rhythms relative to the light cycle remains unchanged. Neural mechanisms downstream from the SCN are therefore believed to determine diurnality or nocturnality. Here, we report a switch from nocturnal to diurnal entrainment of circadian activity rhythms in double-knockout mice lacking the inner-retinal photopigment melanopsin (OPN4) and RPE65, a key protein used in retinal chromophore recycling. These mice retained only a small amount of rod function. The change in entrainment phase of Rpe65−/−;Opn4−/− mice was accompanied by a reversal of the rhythm of clock gene expression in the SCN and a reversal in acute masking effects of both light and darkness on activity, suggesting that the nocturnal to diurnal switch is due to a change in the neural response to light upstream from the SCN. A switch from nocturnal to diurnal activity rhythms was also found in wild-type mice transferred from standard intensity light:dark cycles to light:dark cycles in which the intensity of the light phase was reduced to scotopic levels. These results reveal a novel mechanism by which changes in retinal input can mediate acute temporal-niche switching. PMID:18695249

  3. Retinal oximetry in patients with ischaemic retinal diseases.

    PubMed

    Rilvén, Sandra; Torp, Thomas Lee; Grauslund, Jakob

    2017-03-01

    The retinal oximeter is a new tool for non-invasive measurement of retinal oxygen saturation in humans. Several studies have investigated the associations between retinal oxygen saturation and retinal diseases. In the present systematic review, we examine whether there are associations between retinal oxygen saturation and retinal ischaemic diseases. We used PubMed and Embase to search for retinal oxygen saturation and retinal ischaemic diseases. Three separate searches identified a total of 79 publications. After two levels of manual screening, 10 studies were included: six about diabetic retinopathy (DR) and four about retinal vein occlusion. No studies about retinal artery occlusion were included. In diabetes, all studies found that increases in retinal venous oxygen saturation (rvSatO2 ) were associated with present as well as increasing levels of DR. Four of six studies also found increased retinal arterial oxygen saturation (raSatO2 ) in patients with DR. In patients with central retinal vein occlusion (CRVO), all studies found that rvSatO2 was reduced, but raSatO2 remained unchanged. Branch retinal vein occlusion was not associated with changes in retinal oxygen saturation, but this was based on a single study. In conclusion, DR is associated with increased rvSatO2 and might also be related to increased raSatO2 . Central retinal vein occlusion (CRVO) is correlated with increased rvSatO2 but unrelated to raSatO2 . Prospective studies are needed to expand these findings. These would tell whether retinal oximetry could be a potential tool for screening or a biomarker of treatment outcome in patients with ischaemic retinal diseases.

  4. Receptor mediated disruption of retinal pigment epithelium function in acute glycated-albumin exposure

    PubMed Central

    Dahrouj, Mohammad; Desjardins, Danielle M.; Liu, Yueying; Crosson, Craig E.; Ablonczy, Zsolt

    2015-01-01

    Diabetic macular edema (DME) is a major cause of visual impairment. Although DME is generally believed to be a microvascular disease, dysfunction of the retinal pigment epithelium (RPE) can also contribute to its development. Advanced glycation end-products (AGE) are thought to be one of the key factors involved in the pathogenesis of diabetes in the eye, and we have previously demonstrated a rapid breakdown of RPE function following glycated-albumin (Glyc-alb, a common AGE mimetic) administration in monolayer cultures of fetal human RPE cells. Here we present new evidence that this response is attributed to apically oriented AGE receptors (RAGE). Moreover, time-lapse optical coherence tomography in Dutch-belted rabbits 48 hours post intravitreal Glyc-alb injections demonstrated a significant decrease in RPE-mediated fluid resorption in vivo. In both the animal and tissue culture models, the response to Glyc-alb was blocked by the relatively selective RAGE antagonist, FPS-ZM1 and was also inhibited by ZM323881, a relatively selective vascular endothelial growth factor receptor 2 (VEGF-R2) antagonist. Our data establish that the Glyc-alb-induced breakdown of RPE function is mediated via specific RAGE and VEGF-R2 signaling both in vitro and in vivo. These results are consistent with the notion that the RPE is a key player in the pathogenesis of DME. PMID:26070987

  5. Retinal vein occlusion and the risk of acute myocardial infarction development: a 12-year nationwide cohort study.

    PubMed

    Rim, Tyler Hyungtaek; Han, John Seungsoo; Oh, Jaewon; Kim, Dong Wook; Kang, Seok-Min; Chung, Eun Jee

    2016-02-29

    The goal of this study was to evaluate the risk of developing acute myocardial infarction (AMI) following retinal vein occlusion (RVO). A retrospective cohort study was performed from the National Health Insurance Service and comprised 1,025,340 random subjects who were followed from 2002 to 2013. Patients with RVO in 2002 were excluded. The RVO group was composed of patients who received an initial RVO diagnosis between January 2003 and December 2007 (n = 1677). The comparison group was selected (five patients per RVO patient; n = 8367) using propensity score matching according to sociodemographic factors and the year of enrolment. Each patient was tracked until 2013. The Cox proportional hazard regression model was used. AMI developed in 7.6% of the RVO group and 5.3% of the comparison group (p < 0.001) for 7.7 median follow-up periods. RVO increased the risk of AMI development [hazard ratio (HR) = 1.25; 95% Confidence Interval (CI) 1.02 to 1.52]. In the subgroup analysis, RVO patients aged <65 years and the males within this age group had an adjusted HR of 1.47 (95% CI 1.10 to 1.98) and an adjusted HR of 2.00 (95% CI 1.38 to 2.91) for AMI development, respectively. RVO was significantly associated with AMI development.

  6. Acute retinal necrosis caused by herpes simplex virus type 2 in children: reactivation of an undiagnosed latent neonatal herpes infection.

    PubMed

    Grose, Charles

    2012-09-01

    Herpes simplex virus type 2 (HSV-2) is known to cause acute retinal necrosis (ARN). The availability of HSV-2-specific polymerase chain reaction tests for diagnostic analysis has greatly increased our ability to discriminate ARN caused by HSV-2 from ARN caused by either herpes simplex virus type 1 or varicella zoster virus (VZV). Of great interest, HSV-2 appears to be the most common cause of viral ARN in children and adolescents. Although a few children with ARN are known to have had neonatally acquired herpes infection, most children lack a history of known herpes disease. Thus, the origin of the HSV-2 infection is a mystery. The hypothesis of this review is that HSV-2 ARN in children and adolescents may be the first sign of a previously undiagnosed and asymptomatic neonatal HSV-2 infection, which has reactivated several years later from latency in a cranial nerve and entered the retina. The review brings together 7 previously published ARN cases, plus one new case is added. Thus, this review also expands the spectrum of complications from neonatal HSV-2 infection.

  7. Assessment of Central Retinal Sensitivity Employing Two Types of Microperimetry Devices

    PubMed Central

    Liu, Hongting; Bittencourt, Millena G.; Wang, Jiangxia; Sophie, Raafay; Annam, Rachel; Ibrahim, Mohamed A.; Sepah, Yasir J.; Moradi, Ahmadreza; Scholl, Hendrik P. N.; Nguyen, Quan Dong

    2014-01-01

    Purpose To compare the retinal sensitivity measurements obtained with two microperimeters, the Micro-Perimeter 1 (MP-1) and the Optos optical coherence tomography (OCT)/scanning laser ophthalmoscope (SLO) in subjects with and without maculopathies. Methods Forty-five eyes with no known ocular disease and 47 eyes with maculopathies were examined using both microperimeters. A contrast-adjusted scale was applied to resolve the different stimuli and background luminance existing between the two devices. Results There was a strong ceiling effect with the MP-1 in the healthy group, with 90.1% (1136 of 1260) test points clustered at 20 dB. The mean sensitivity for the corresponding points in the OCT/SLO was 25.8 ± 1.9 dB. A floor effect was also observed with the OCT/SLO in the maculopathy group with 9.7% (128 of 1316) points clustered at 9-dB values. The corresponding mean sensitivity in the MP-1 was 1.7 ± 3.9 dB. A regression equation between the two microperimeters was established in the common 10 to19 dB intervals as: OCT/SLO = 15.6 + 0.564 × MP-1 − 0.009 × MP-12 + k (k is an individual point constant; MP-1 coefficient P < 0.001; MP-12 coefficient P = 0.006). Conclusion The OCT/SLO and the MP-1 provide two different ranges of contrasts for microperimetry examination. Broadening the dynamic range may minimize the constraint of the ceiling and floor effect. There is a significant mathematical relationship in the common interval of the contrast scale. Translational Relevance Applying a unified and broadened dynamic range in different types of microperimeters will help to generate consistent clinical reference for measurements. PMID:25237592

  8. [Application of retinal oximeter in ophthalmology].

    PubMed

    Li, Jing; Ma, Jianmin; Wang, Ningli

    2015-11-01

    Retinal oximeter is a new machine which has been used in the diagnose, treatment and research of several ophthalmic diseases for recent years. It allows ophthalmologists to gain retinal oxygen saturation directly. Therefore, retinal oximeter might be useful for ophthalmologists to understand ophthalmic diseases more deeper and clarify the impact of ischemia on retinal function. It has been reported in the literatures that retinal oximeter has potentially useful diagnostic and therapeutic indications in various eye diseases such as diabetic retinopathy, central retinal vein and artery occlusion, retinitis pigmentosa, glaucomatous optic neuropathy, et al. In this thesis, the application of retinal oximeter in ophthalmology is reviewed.

  9. Intracellular Signalling in Retinal Ischemia

    DTIC Science & Technology

    1990-07-01

    36) However, vascularization of the RPE is not known to occur in human diseases of photoreceptor degeneration, such as retinitis pigmentosa ...A.C. (1986) Retinitis pigmentosa and retinal neovascularization. Ophthalmology 91, 1599- 1603. Figure la: Control rat retina, 8 weeks of age, central...TITLE (Include Security Classification) Intracellular Signalling in Retinal Ischemia 12. PERSONAL AUTHOR(S) Burns, Margaret Sue; Bellhorn, Roy William

  10. So-called "central retinal vein occlusion". II. Venous stasis retinopathy.

    PubMed

    Hayreh, S S

    1976-01-01

    28 patients (29 eyes) with venous stasis retinopathy (VSR) were studied. This study indicates that VSR is a self-limited, chronic and comparatively benign condition as compared to hemorrhagic retinopathy. No patient with VSR progressed to hemorrhagic retinopathy. The main complication which required management in VSR was the deterioration of central visual acuity (VA) due to development of macular edema which, if untreated, ended in cystoid macular degeneration and permanent central scotoma. Thus the indication for treatment in these cases was the fall of central VA. Ten eyes showed no deterioration of vision throughout follow-up (group I) and hence required no treatment. The remaining 19 eyes developed deterioration of vision: 5 eyes (4 patients) amongst these were not treated (group II) while the other 14 eyes (group III) were treated by systemic corticosteroids, to control the macula edema starting with a dose of 40-60 mg of oral prednisolone daily and gradually tapering to a maintenance dose. The results of group III cases strongly suggested that adequate doses of systemic steroids have a distinct beneficial effect on the VA -they help to prevent deterioration of vision and in the recovery of deteriorated vision. However, these patients require therapy for months or even longer during the course of VSR; on stopping the therapy, poor VA recurred in ten of these eyes. This factor may limit the usefulness of this therapy, if contraindications to such prolonged steriod therapy or serious side-effects of steroid therapy exist in a patient. In such cases one may be confronted with the dilemma of either not treating them and running a fairly high risk of permanent loss of central vision, or treating them with adequate doses of systemic steriods, retaining good VA but running the risk of side effects. While evaluating the effectiveness of steroid therapy, the improvement in VA should be the primary criterion because the fundus appearances almost always show no

  11. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells

    PubMed Central

    Di Lauro, Salvatore; Rodriguez-Crespo, David; Gayoso, Manuel J.; Garcia-Gutierrez, Maria T.; Pastor, J. Carlos; Srivastava, Girish K.

    2016-01-01

    Purpose To develop and standardize a novel organ culture model using porcine central neuroretina explants and RPE cells separated by a cell culture membrane. Methods RPE cells were isolated from porcine eyes, expanded, and seeded on the bottom of cell culture inserts. Neuroretina explants were obtained from the area centralis and cultured alone (controls) on cell culture membranes or supplemented with RPE cells in the same wells but physically separated by the culture membrane. Finally, cellular and tissue specimens were processed for phase contrast, cyto-/histological, and immunochemical evaluation. Neuroretina thickness was also determined. Results Compared to the neuroretinas cultured alone, the neuroretinas cocultured with RPE cells maintained better tissue structure and cellular organization, displayed better preservation of photoreceptors containing rhodopsin, lower levels of glial fibrillary acidic protein immunoexpression, and preservation of cellular retinaldehyde binding protein both markers of reactive gliosis. Neuroretina thickness was significantly greater in the cocultures. Conclusions A coculture model of central porcine neuroretina and RPE cells was successfully developed and standardized. This model mimics a subretinal space and will be useful in studying interactions between the RPE and the neuroretina and to preclinically test potential therapies. PMID:27081295

  12. Hyperoxia causes reduced density of retinal astrocytes in the central avascular zone in the mouse model of oxygen-induced retinopathy.

    PubMed

    Bucher, Felicitas; Stahl, Andreas; Agostini, Hansjürgen T; Martin, Gottfried

    2013-09-01

    The mouse model of oxygen-induced retinopathy (OIR) is commonly used to investigate various aspects of the pathogenesis of the retinopathy of prematurity (ROP) as well as angiogenesis in general. Retinal astrocytes were suggested to be involved in retinal angiogenesis. This study aimed to describe their localization and cell density during the course of physiological vascularization and pathological revascularization. Mice expressing H2B-GFP (green fluorescent protein fused to histone 2B) from the endogenous Pdgfra promoter were kept in 75% oxygen from P7 (post natal day 7) to P12 (mouse model of OIR). Retinal flatmounts or cryosections were immunostained for glial fibrillary acidic protein (Gfap), glutamine synthetase (Glul), collagen IV (Col IV), desmin (Des), caspase 3 (Casp3), paired box 2 (Pax2), or Ki67. Astrocytic nuclei were counted with the ImageJ macro AuTOCellQuant. The hypoxic state of the retina was investigated by Hypoxyprobe. The GFP signal of the Pdgfra reporter mice co-localized with Pax2, a nuclear marker for retinal astrocytes. This bright label was much easier to quantify than Gfap or Pax2 staining. Quantification of the cell density of astrocytes during physiological development specified the spreading of astrocytes in a concentrical wave from the optic nerve head towards the periphery. Astrocyte density was reduced during the remodelling of the primary vascular plexus into a hierarchical vascular tree (maximal astrocyte density at P1: 2800 astrocytes/mm2, final astrocyte density: 800 astrocytes/mm2). In the OIR model, cell density of astrocytes was elevated in the peripheral vascularized zone. In contrast, astrocyte density dropped to a half (400 astrocytes/mm2) of the normal value in the central avascular zone during the hyperoxic phase between P8 and P10 by apoptosis and rose only after P17 as the retinal network normalized. An additional drop of astrocyte density was observed within the angles between the large vessels of the central

  13. Retinal locus for scanning text.

    PubMed

    Timberlake, George T; Sharma, Manoj K; Grose, Susan A; Maino, Joseph H

    2006-01-01

    A method of mapping the retinal location of text during reading is described in which text position is plotted cumulatively on scanning laser ophthalmoscope retinal images. Retinal locations that contain text most often are the brightest in the cumulative plot, and locations that contain text least often are the darkest. In this way, the retinal area that most often contains text is determined. Text maps were plotted for eight control subjects without vision loss and eight subjects with central scotomas from macular degeneration. Control subjects' text maps showed that the fovea contained text most often. Text maps of five of the subjects with scotomas showed that they used the same peripheral retinal area to scan text and fixate. Text maps of the other three subjects with scotomas showed that they used separate areas to scan text and fixate. Retinal text maps may help evaluate rehabilitative strategies for training individuals with central scotomas to use a particular retinal area to scan text.

  14. The role of ZAP70 kinase in acute lymphoblastic leukemia infiltration into the central nervous system.

    PubMed

    Alsadeq, Ameera; Fedders, Henning; Vokuhl, Christian; Belau, Nele M; Zimmermann, Martin; Wirbelauer, Tim; Spielberg, Steffi; Vossen-Gajcy, Michaela; Cario, Gunnar; Schrappe, Martin; Schewe, Denis M

    2017-02-01

    Central nervous system infiltration and relapse are poorly understood in childhood acute lymphoblastic leukemia. We examined the role of zeta-chain-associated protein kinase 70 in preclinical models of central nervous system leukemia and performed correlative studies in patients. Zeta-chain-associated protein kinase 70 expression in acute lymphoblastic leukemia cells was modulated using short hairpin ribonucleic acid-mediated knockdown or ectopic expression. We show that zeta-chain-associated protein kinase 70 regulates CCR7/CXCR4 via activation of extracellular signal-regulated kinases. High expression of zeta-chain-associated protein kinase 70 in acute lymphoblastic leukemia cells resulted in a higher proportion of central nervous system leukemia in xenografts as compared to zeta-chain-associated protein kinase 70 low expressing counterparts. High zeta-chain-associated protein kinase 70 also enhanced the migration potential towards CCL19/CXCL12 gradients in vitro CCR7 blockade almost abrogated homing of acute lymphoblastic leukemia cells to the central nervous system in xenografts. In 130 B-cell precursor acute lymphoblastic leukemia and 117 T-cell acute lymphoblastic leukemia patients, zeta-chain-associated protein kinase 70 and CCR7/CXCR4 expression levels were significantly correlated. Zeta-chain-associated protein kinase 70 expression correlated with central nervous system disease in B-cell precursor acute lymphoblastic leukemia, and CCR7/CXCR4 correlated with central nervous system involvement in T-cell acute lymphoblastic leukemia patients. In multivariate analysis, zeta-chain-associated protein kinase 70 expression levels in the upper third and fourth quartiles were associated with central nervous system involvement in B-cell precursor acute lymphoblastic leukemia (odds ratio=7.48, 95% confidence interval, 2.06-27.17; odds ratio=6.86, 95% confidence interval, 1.86-25.26, respectively). CCR7 expression in the upper fourth quartile correlated with central

  15. The role of ZAP70 kinase in acute lymphoblastic leukemia infiltration into the central nervous system

    PubMed Central

    Alsadeq, Ameera; Fedders, Henning; Vokuhl, Christian; Belau, Nele M.; Zimmermann, Martin; Wirbelauer, Tim; Spielberg, Steffi; Vossen-Gajcy, Michaela; Cario, Gunnar; Schrappe, Martin; Schewe, Denis M.

    2017-01-01

    Central nervous system infiltration and relapse are poorly understood in childhood acute lymphoblastic leukemia. We examined the role of zeta-chain-associated protein kinase 70 in preclinical models of central nervous system leukemia and performed correlative studies in patients. Zeta-chain-associated protein kinase 70 expression in acute lymphoblastic leukemia cells was modulated using short hairpin ribonucleic acid-mediated knockdown or ectopic expression. We show that zeta-chain-associated protein kinase 70 regulates CCR7/CXCR4 via activation of extracellular signal-regulated kinases. High expression of zeta-chain-associated protein kinase 70 in acute lymphoblastic leukemia cells resulted in a higher proportion of central nervous system leukemia in xenografts as compared to zeta-chain-associated protein kinase 70 low expressing counterparts. High zeta-chain-associated protein kinase 70 also enhanced the migration potential towards CCL19/CXCL12 gradients in vitro. CCR7 blockade almost abrogated homing of acute lymphoblastic leukemia cells to the central nervous system in xenografts. In 130 B-cell precursor acute lymphoblastic leukemia and 117 T-cell acute lymphoblastic leukemia patients, zeta-chain-associated protein kinase 70 and CCR7/CXCR4 expression levels were significantly correlated. Zeta-chain-associated protein kinase 70 expression correlated with central nervous system disease in B-cell precursor acute lymphoblastic leukemia, and CCR7/CXCR4 correlated with central nervous system involvement in T-cell acute lymphoblastic leukemia patients. In multivariate analysis, zeta-chain-associated protein kinase 70 expression levels in the upper third and fourth quartiles were associated with central nervous system involvement in B-cell precursor acute lymphoblastic leukemia (odds ratio=7.48, 95% confidence interval, 2.06–27.17; odds ratio=6.86, 95% confidence interval, 1.86–25.26, respectively). CCR7 expression in the upper fourth quartile correlated with

  16. No influence of acute RF exposure (GSM-900, GSM-1800, and UMTS) on mouse retinal ganglion cell responses under constant temperature conditions.

    PubMed

    Ahlers, Malte T; Ammermüller, Josef

    2014-01-01

    Possible non-thermal effects of radio frequency electromagnetic fields (RF-EMF) on retinal ganglion cells were studied in vitro under conditions of constant temperature. Isolated mouse retinae were exposed to GSM-900, GSM-1800, and universal mobile telecommunication system (UMTS) RF-EMF applying specific absorption rates (SAR) of 0 (sham), 0.02, 0.2, 2, and 20 W/kg. Temperature was kept constant within ±0.5 to 1 °C for GSM-900 and ±0.5 °C for GSM-1800 and UMTS. Responses of retinal ganglion cells to light stimuli of three intensities (0.5, 16, and 445 lx) were recorded before, during, and up to 35 min after exposure. Experiments were performed under double-blind conditions. Changes in light responses during and after exposure were determined for each condition (RF-EMF; SAR value; light intensity) with respect to the responses before exposure, respectively. Changes were calculated using the Euclidian distance of the n-dimensional response vectors, respectively. Some changes already occurred during sham (0 W/kg) exposure, reflecting the intrinsic variability in retinal ganglion cell responses. Comparison of the distance values from sham exposure with those from actual exposure yielded no significant differences. In addition, linear regression analysis of the distance values versus SAR values yielded no consistent dependence of light response changes. From these results we conclude that RF-EMF exposure at three mobile phone frequencies (GSM-900, GSM-1800, UMTS) and SARs up to 20 W/kg has no acute effects on retinal ganglion cell responses under constant temperature conditions.

  17. α-Aminoadipic acid protects against retinal disruption through attenuating Müller cell gliosis in a rat model of acute ocular hypertension

    PubMed Central

    Wang, Xiaolei; Su, Jier; Ding, Jingwen; Han, Song; Ma, Wei; Luo, Hong; Hughes, Guy; Meng, Zhaoyang; Yin, Yi; Wang, Yanling; Li, Junfa

    2016-01-01

    Objective Ocular hypertension is an important risk factor for glaucoma. The purpose of this study was to investigate the gliotoxic effects of α-aminoadipic acid (AAA) in a rat model of AOH and its underlying mechanisms. Materials and methods In the rat model of acute ocular hypertension (AOH), intraocular pressure was increased to 110 mmHg for 60 minutes. Animals were divided into four groups: sham operation (Ctrl), AOH, AOH + phosphate-buffered saline (PBS), and AOH + AAA. Cell apoptosis in the ganglion cell layer was detected with the terminal deoxynucleotidyl transferase-mediated uridine 5′-triphosphate-biotin nick end labeling (TUNEL) assay, and retinal ganglion cells (RGCs) immunostained with Thy-1 were counted. Müller cell activation was detected using immunostaining with glutamine synthetase and glial fibrillary acidic protein. Tumor necrosis factor-α (TNF-α) was examined using Western blot. Results In the rat model of AOH, cell apoptosis was induced in the ganglion cell layer and the number of RGCs was decreased. Müller cell gliosis in the retinas of rats was induced, and retinal protein levels of TNF-α were increased. Intravitreal treatment of AAA versus PBS control attenuated these retinal abnormalities to show protective effects in the rat model of AOH. Conclusion In the retinas of the rat model of AOH, AAA treatment attenuated retinal apoptosis in the ganglion cell layer and preserved the number of RGCs, likely through the attenuation of Müller cell gliosis and suppression of TNF-α induction. Our observations suggest that AAA might be a potential therapeutic target in glaucoma. PMID:27799744

  18. Factors Associated with the Retinal Nerve Fiber Layer Loss after Acute Primary Angle Closure: A Prospective EDI-OCT Study

    PubMed Central

    Lee, Kyoung Min; Lee, Seung Hyen; Kim, Hyunjoong

    2017-01-01

    Purpose To determine the factors associated with retinal nerve fiber layer (RNFL) loss in eyes with acute primary angle-closure (APAC), particularly focusing on the influence of the change in the anterior lamina cribrosa surface depth (LCD). Methods After the initial presentation, 30 eyes with unilateral APAC were followed up at the following specific time points over a 12-month period: 1 week, 1~2 months, 2~3 months, 5~6 months, and 11~12 months. These follow-ups involved intraocular pressure measurements, enhanced depth-imaging spectral-domain optical coherence tomography (SD-OCT) scanning of the optic disc, and measurements of the circumpapillary RNFL thickness. The prelaminar tissue thickness (PLT) and LCD were determined in the SD-OCT images obtained at each follow-up visit. Results Repeated measures analysis of variance revealed a significant pattern of decrease in the global RNFL thickness, PLT, and LCD (all p<0.001). The global RNFL thickness decreased continuously throughout the follow-up period, while the PLT decreased until 5~6 months and did not change thereafter. The LCD reduced until 2~3 months and then also remained steady. Multivariable regression analysis revealed that symptoms with a longer duration before receiving laser peripheral iridotomy (LI) (p = 0.049) and a larger LCD reduction (p = 0.034) were significant factors associated with the conversion to an abnormal RNFL thickness defined using OCT normative data. Conclusion Early short-term decreases in the PLT and LCD and overall long-term decrease in the peripapillary RNFL were observed during a 12-month follow-up after an APAC episode. A longer duration of symptoms before receiving LI treatment and larger LCD reduction during follow-up were associated with the progressive RNFL loss. The LCD reduction may indicate a prior presence of significant pressure-induced stress that had been imposed on the optic nerve head at the time of APAC episode. Glaucomatous progression should be suspected in

  19. Retinitis Pigmentosa and Other Dystrophies.

    PubMed

    Mrejen, Sarah; Audo, Isabelle; Bonnel, Sébastien; Sahel, José-Alain

    2017-01-01

    Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal degenerations characterized by progressive degeneration of rod and cone cells that affects predominantly peripheral visual fields. Macular edema may cause additional central visual acuity decrease. Cystoid macular edema (CME) is one of the few treatable causes of visual loss in RP. The prevalence of CME in RP has been found to be between 10 and 20% on fluorescein angiography-based studies, and as high as 49% on reports based on optical coherence tomography. Macular edema can manifest at any stage of the disease and may be unilateral or bilateral. It can be found in any genetic form, but is more often associated with RP caused by CRB1 mutations. The origin of macular edema in RP patients still remains poorly understood. Some mechanisms have been suggested, including antiretinal antibodies (retinal, carbonic anhydrase, and enolase antibodies), vitreous traction, retinal pigment epithelium dysfunction, and Müller cell edema. There is no gold standard therapeutic strategy. Drug therapy is the primary treatment. Systemic carbonic anhydrase inhibitors, such as oral acetazolamide or topical dorzolamide, are still the mainstays of initial therapy. If CME is refractory to acetazolamide, intravitreal corticosteroid injections may be a therapeutic option. However, antivascular endothelium growth factor injections have limited effect and should be avoided. Vitrectomy has also been evaluated, but its exact role remains to be determined. The benefits of these therapies are variable among patients. The establishment of therapeutic approaches is limited by our poor understanding of the pathophysiology of CME in patients with RP. Autoimmune retinopathies (AIRs) are a group of rare diseases characterized by acute or subacute progressive vision loss and are thought to be mediated by autoantibodies specific to retinal antigens. The AIRs encompass paraneoplastic syndromes, such as cancer-associated retinopathy and

  20. Cross-sectional study of the retinal nerve fiber layer thickness at 7 years after an acute episode of unilateral primary acute angle closure.

    PubMed

    Lee, Jacky W Y; Woo, Tiffany T Y; Yau, Gordon S K; Yip, Stan; Yick, Doris W F; Wong, Jasper; Wong, Raymond L M; Wong, Ian Y H

    2015-01-01

    The purpose of this article is to investigate the long-term retinal nerve fiber layer (RNFL) status and determinants of RNFL thinning after an episode of unilateral primary acute angle closure (AAC). This cross-sectional study analyzed the medical records of consecutive patients with a single episode of unilateral AAC from 1999 to 2009 in Hong Kong. The peripapillary RNFL thickness was correlated with age, gender, presenting intraocular pressure (IOP), time to laser iridotomy, time to cataract extraction, follow-up duration, as well as the last IOP, vertical cup-to-disc ratio (CDR), and vision. The fellow uninvolved eye was used as a proxy comparison of RNFL loss in the attack eye. In 40 eligible patients, the mean age was 68.3 ± 8.7 years with a male-to-female ratio of 1:7. The mean presenting IOP was 49.2 ± 14.0 mm Hg and the time from presentation to laser iridotomy was 6.7 ± 6.9 days. Forty percent of subjects received a cataract extraction at 3.2 ± 2.9 years after the attack. The last IOP, CDR, and LogMAR vision were 16.0 ± 3.8 mm Hg, 0.6 ± 0.2, and 0.6 ± 0.6 LogMAR units, respectively, at 7.9 ± 2.4 years. The RNFL thickness in the attack eye (69.2 ± 19.1 μm) was 25.2 ± 17.9% thinner than the fellow eye (93.0 ± 17.8 μm) at 7.5 ± 2.9 years post-AAC. Using univariate analysis, the last vertical CDR (odds ratio [OR] = 17.2, P = 0.049) and LogMAR visual acuity (VA) (OR = 6.6, P = 0.03) were the only significant predictors for RNFL thinning whereas none of the other covariates showed significant associations (P > 0.1). At 7.5 years following unilateral AAC, the RNFL thickness was 25% thinner than the fellow eye. CDR enlargement and poor VA were the only significant predictors for RNFL loss.

  1. Retinal proteins associated with redox regulation and protein folding play central roles in response to high glucose conditions.

    PubMed

    Wang, Ssu-Han; Lee, Wen-Chi; Chou, Hsiu-Chuan

    2015-03-01

    Diabetic retinopathy typically causes poor vision and blindness. A previous study revealed that a high blood glucose concentration induces glycoxidation and weakens the retinal capillaries. Nevertheless, the molecular mechanisms underlying the effects of high blood glucose induced diabetic retinopathy remain to be elucidated. In the present study, we cultured the retinal pigmented epithelial cell line ARPE-19 in mannitol-balanced 5.5, 25, and 100 mM glucose media and investigated protein level alterations. Proteomic analysis revealed significant changes in 137 protein features, of which 124 demonstrated changes in a glucose concentration dependent manner. Several proteins functionally associated with redox regulation, protein folding, or the cytoskeleton are affected by increased glucose concentrations. Additional analyses also revealed that cellular oxidative stress, including endoplasmic reticulum stress, was significantly increased after treatment with high glucose concentrations. However, the mitochondrial membrane potential and cell survival remained unchanged during treatment with high glucose concentrations. To summarize, in this study, we used a comprehensive retinal pigmented epithelial cell based proteomic approach for identifying changes in protein expression associated retinal markers induced by high glucose concentrations. Our results revealed that a high glucose condition can induce cellular oxidative stress and modulate the levels of proteins with functions in redox regulation, protein folding, and cytoskeleton regulation; however, cell viability and mitochondrial integrity are not significantly disturbed under these high glucose conditions.

  2. Phosphatase control of 4E-BP1 phosphorylation state is central for glycolytic regulation of retinal protein synthesis.

    PubMed

    Gardner, Thomas W; Abcouwer, Steven F; Losiewicz, Mandy K; Fort, Patrice E

    2015-09-15

    Control of protein synthesis in insulin-responsive tissues has been well characterized, but relatively little is known about how this process is regulated in nervous tissues. The retina exhibits a relatively high protein synthesis rate, coinciding with high basal Akt and metabolic activities, with the majority of retinal ATP being derived from aerobic glycolysis. We examined the dependency of retinal protein synthesis on the Akt-mTOR signaling and glycolysis using ex vivo rat retinas. Akt inhibitors significantly reduced retinal protein synthesis but did not affect glycolytic lactate production. Surprisingly, the glycolytic inhibitor 2-deoxyglucose (2-DG) markedly inhibited Akt1 and Akt3 activities, as well as protein synthesis. The effects of 2-DG, and 2-fluorodeoxyglucose (2-FDG) on retinal protein synthesis correlated with inhibition of lactate production and diminished ATP content, with all these effects reversed by provision of d-mannose. 2-DG treatment was not associated with increased AMPK, eEF2, or eIF2α phosphorylation; instead, it caused rapid dephosphorylation of 4E-BP1. 2-DG reduced total mTOR activity by 25%, but surprisingly, it did not reduce mTORC1 activity, as indicated by unaltered raptor-associated mTOR autophosphorylation and ribosomal protein S6 phosphorylation. Dephosphorylation of 4E-BP1 was largely prevented by inhibition of PP1/PP2A phosphatases with okadaic acid and calyculin A, and inhibition of PPM1 phosphatases with cadmium. Thus, inhibition of retinal glycolysis diminished Akt and protein synthesis coinciding with accelerated dephosphorylation of 4E-BP1 independently of mTORC1. These results demonstrate a novel mechanism regulating protein synthesis in the retina involving an mTORC1-independent and phosphatase-dependent regulation of 4E-BP1.

  3. Acute Hemorrhagic Retinopathy following Intravitreal Melphalan Injection for Retinoblastoma: A Report of Two Cases and Technical Modifications to Enhance the Prevention of Retinal Toxicity

    PubMed Central

    Aziz, Hassan A.; Kim, Jonathan W.; Munier, Francis L.; Berry, Jesse L.

    2017-01-01

    Aims To report the occurrence of acute hemorrhagic retinopathy following intravitreal melphalan injection for retinoblastoma. Methods This is a retrospective case series of 2 patients with retinoblastoma treated with intravitreal melphalan for vitreous seeding who developed acute hemorrhagic retinopathy. Results Patient 1 is a 6-month-old female with bilateral retinoblastoma (Group D right eye and Group B left eye) treated with 4 cycles of systemic chemotherapy and 2 intravitreal melphalan injections in each eye. Patient 2 is a 10-month-old male with unilateral Group D retinoblastoma treated with 6 cycles of systemic chemotherapy and 2 injections of intravitreal melphalan. At the 1-week follow-up after the second injection, both patients had an acute hemorrhagic retinopathy that resulted in chorioretinal toxicity with a sharp demarcation line between the normal and abnormal retina. At the last follow-up (22 and 12 months, respectively), there was total tumor control and resolution of vitreous seeding in both patients. Conclusions Although intravitreal melphalan injection is effective for vitreous seeding in eyes with retinoblastoma, acute hemorrhagic retinopathy and diffuse chorioretinal atrophy is a possible complication of this treatment modality. Given the clinical findings observed in these patients, the development of this retinal toxicity most likely results from a retrohyaloid overdose. Consequently we suggest preventive measures aimed at limiting the risk of retrohyaloid injection.

  4. Retinitis Pigmentosa.

    ERIC Educational Resources Information Center

    Carr, Ronald E.

    1979-01-01

    The author describes the etiology of retinitis pigmentosa, a visual dysfunction which results from progressive loss of the retinal photoreceptors. Sections address signs and symptoms, ancillary findings, heredity, clinical diagnosis, therapy, and research. (SBH)

  5. Retinitis pigmentosa

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/001029.htm Retinitis pigmentosa To use the sharing features on this page, please enable JavaScript. Retinitis pigmentosa is an eye disease in which there is ...

  6. Retinal Detachment

    MedlinePlus

    ... men more than women and whites more than African Americans. A retinal detachment is also more likely to occur in people who Are extremely nearsighted Have had a retinal detachment in the other eye Have a family history of retinal detachment Have had cataract surgery Have ...

  7. Acute pesticide poisoning and pesticide registration in Central America

    SciTech Connect

    Wesseling, Catharina . E-mail: cwesseli@una.ac.cr; Corriols, Marianela; Bravo, Viria

    2005-09-01

    The International Code of Conduct on the Distribution and Use of Pesticides of the Food and Agriculture Organization (FAO) of the United Nations has been for 20 years the most acknowledged international initiative for reducing negative impact from pesticide use in developing countries. We analyzed pesticide use and poisoning in Central America, particularly in Costa Rica and Nicaragua, and evaluated whether registration decisions are based on such data, in accordance with the FAO Code. Extensive use of very hazardous pesticides continues in Central America and so do poisonings with organophosphates, carbamates, endosulfan and paraquat as the main causative agents. Central American governments do not carry out or commission scientific risk assessments. Instead, guidelines from international agencies are followed for risk management through the registration process. Documentation of pesticide poisonings during several decades never induced any decision to ban or restrict a pesticide. However, based on the official surveillance systems, in 2000, the ministers of health of the seven Central American countries agreed to ban or restrict twelve of these pesticides. Now, almost 4 years later, restrictions have been implemented in El Salvador and in Nicaragua public debate is ongoing. Chemical and agricultural industries do not withdraw problematic pesticides voluntarily. In conclusion, the registration processes in Central America do not comply satisfactorily with the FAO Code. However, international regulatory guidelines are important in developing countries, and international agencies should strongly extend its scope and influence, limiting industry involvement. Profound changes in international and national agricultural policies, steering towards sustainable agriculture based on non-chemical pest management, are the only way to reduce poisonings.

  8. Ruptured retinal arterial macroaneurysm: diagnosis and management.

    PubMed

    Speilburg, Ashley M; Klemencic, Stephanie A

    2014-01-01

    Retinal arterial macroaneurysm is an acquired, focal dilation of a retinal artery, typically occurring within the first three bifurcations of the central retinal artery. The clinical presentation of a retinal arterial macroaneurysm is highly variable, making initial diagnosis difficult and differentials many. Identification of retinal arterial macroaneurysms is crucial to appropriately co-manage with the primary care physician for hypertension control. Prognosis is generally good and observation is often an adequate treatment. However, in cases of macular threat or involvement, some treatment options are available and referral to a retinal specialist is indicated.

  9. The visual system of a palaeognathous bird: visual field, retinal topography and retino-central connections in the Chilean tinamou (Nothoprocta perdicaria).

    PubMed

    Krabichler, Quirin; Vega-Zuniga, Tomas; Morales, Cristian; Luksch, Harald; Marín, Gonzalo J

    2015-02-01

    Most systematic studies of the avian visual system have focused on Neognathous species, leaving virtually unexplored the Palaeognathae, comprised of the flightless ratites and the South American tinamous. We investigated the visual field, the retinal topography, and the pattern of retinal and centrifugal projections in the Chilean tinamou, a small Palaeognath of the family Tinamidae. The tinamou has a panoramic visual field with a small frontal binocular overlap of 20°. The retina possesses three distinct topographic specializations: a horizontal visual streak, a dorsotemporal area, and an area centralis with a shallow fovea. The maximum ganglion cell density is 61,900/ mm(2) , comparable to Falconiformes. This would provide a maximal visual acuity of 14.0 cycles/degree, in spite of relatively small eyes. The central retinal projections generally conform to the characteristic arrangement observed in Neognathae, with well-differentiated contralateral targets and very few ipsilateral fibers. The centrifugal visual system is composed of a considerable number of multipolar centrifugal neurons, resembling the "ectopic" neurons described in Neognathae. They form a diffuse nuclear structure, which may correspond to the ancestral condition shared with other sauropsids. A notable feature is the presence of terminals in deep tectal layers 11-13. These fibers may represent either a novel retinotectal pathway or collateral branches from centrifugal neurons projecting to the retina. Both types of connections have been described in chicken embryos. Our results widen the basis for comparative studies of the vertebrate visual system, stressing the conserved character of the visual projections' pattern within the avian clade.

  10. Acute Sheehan's syndrome presenting as central diabetes insipidus

    PubMed Central

    Robalo, Raquel; Pedroso, Célia; Agapito, Ana; Borges, Augusta

    2012-01-01

    Sheehan's syndrome occurs as a result of ischaemic pituitary necrosis due to severe postpartum haemorrhage. Improvements in obstetrical care have significantly reduced its incidence in developed countries, but postpartum pituitary infarction remains a common cause of hypopituitarism in developing countries. We report a case of severe postpartum haemorrhage followed by headache, central diabetes insipidus and failure to lactate, which prompted us to investigate and identify both anterior and posterior pituitary deficiency compatible with Sheehan's syndrome. A timely diagnosis allowed us to implement an adequate treatment and follow-up plan, which are known to improve clinical status and patient outcome. PMID:23131607

  11. Acute Sheehan's syndrome presenting as central diabetes insipidus.

    PubMed

    Robalo, Raquel; Pedroso, Célia; Agapito, Ana; Borges, Augusta

    2012-11-06

    Sheehan's syndrome occurs as a result of ischaemic pituitary necrosis due to severe postpartum haemorrhage. Improvements in obstetrical care have significantly reduced its incidence in developed countries, but postpartum pituitary infarction remains a common cause of hypopituitarism in developing countries. We report a case of severe postpartum haemorrhage followed by headache, central diabetes insipidus and failure to lactate, which prompted us to investigate and identify both anterior and posterior pituitary deficiency compatible with Sheehan's syndrome. A timely diagnosis allowed us to implement an adequate treatment and follow-up plan, which are known to improve clinical status and patient outcome.

  12. Central Venous Line and Acute Neurological Deficit: A Case Series

    PubMed Central

    Ahmadi, Seyed Hossein; Shirzad, Mahmood; Zeraatian, Sam; Salehiomran, Abbas; Abbasi, Seyed Hesameddin; Ghiasi, Atefeh

    2014-01-01

    Abstract Central venous catheter (CVC) insertion is a practical way to assess patients hemodynamic specially in cardiovascular surgery but this relatively simple junior level procedure is not risk free and its common reported complications include; pneumothorax, hydrothorax, hemothorax, local hematoma, cardiac tamponade, vascular injury, thrombosis, embolism, and catheter disruption. Here in this article we are going to present 6 patients with very unusual presentation of CVC complication which was neurological deficit presented by agitation, unconsciousness, disorientation to time and place and hemiparesis. All patients undergone neurologic consult and brain computed tomography. Final diagnosis was brain ischemic damage and finally we kept them on conservative management; fortunately we did not have any permanent damage. PMID:25870645

  13. Learning about Retinitis Pigmentosa

    MedlinePlus

    ... genetic terms used on this page Learning About Retinitis Pigmentosa What is retinitis pigmentosa? What are the symptoms ... Pigmentosa Additional Resources for Retinitis Pigmentosa What is retinitis pigmentosa? Retinitis pigmentosa (RP) is the name given to ...

  14. Driving with Central Visual Field Loss II: How Scotomas above or below the Preferred Retinal Locus (PRL) Affect Hazard Detection in a Driving Simulator

    PubMed Central

    Bowers, Alex R.; Goldstein, Robert; Peli, Eli

    2015-01-01

    We determined whether binocular central scotomas above or below the preferred retinal locus affect detection of hazards (pedestrians) approaching from the side. Seven participants with central field loss (CFL), and seven age-and sex-matched controls with normal vision (NV), each completed two sessions of 5 test drives (each approximately 10 minutes long) in a driving simulator. Participants pressed the horn when detecting pedestrians that appeared at one of four eccentricities (-14°, -4°, left, 4°, or 14°, right, relative to car heading). Pedestrians walked or ran towards the travel lane on a collision course with the participant’s vehicle, thus remaining in the same area of the visual field, assuming participant's steady forward gaze down the travel lane. Detection rates were nearly 100% for all participants. CFL participant reaction times were longer (median 2.27s, 95% CI 2.13 to 2.47) than NVs (median 1.17s, 95%CI 1.10 to 2.13; difference p<0.01), and CFL participants would have been unable to stop for 21% of pedestrians, compared with 3% for NV, p<0.001. Although the scotomas were not expected to obscure pedestrian hazards, gaze tracking revealed that scotomas did sometimes interfere with detection; late reactions usually occurred when pedestrians were entirely or partially obscured by the scotoma (time obscured correlated with reaction times, r = 0.57, p<0.001). We previously showed that scotomas lateral to the preferred retinal locus delay reaction times to a greater extent; however, taken together, the results of our studies suggest that any binocular CFL might negatively impact timely hazard detection while driving and should be a consideration when evaluating vision for driving. PMID:26332315

  15. Driving with Central Visual Field Loss II: How Scotomas above or below the Preferred Retinal Locus (PRL) Affect Hazard Detection in a Driving Simulator.

    PubMed

    Bronstad, P Matthew; Albu, Amanda; Bowers, Alex R; Goldstein, Robert; Peli, Eli

    2015-01-01

    We determined whether binocular central scotomas above or below the preferred retinal locus affect detection of hazards (pedestrians) approaching from the side. Seven participants with central field loss (CFL), and seven age-and sex-matched controls with normal vision (NV), each completed two sessions of 5 test drives (each approximately 10 minutes long) in a driving simulator. Participants pressed the horn when detecting pedestrians that appeared at one of four eccentricities (-14°, -4°, left, 4°, or 14°, right, relative to car heading). Pedestrians walked or ran towards the travel lane on a collision course with the participant's vehicle, thus remaining in the same area of the visual field, assuming participant's steady forward gaze down the travel lane. Detection rates were nearly 100% for all participants. CFL participant reaction times were longer (median 2.27s, 95% CI 2.13 to 2.47) than NVs (median 1.17s, 95%CI 1.10 to 2.13; difference p<0.01), and CFL participants would have been unable to stop for 21% of pedestrians, compared with 3% for NV, p<0.001. Although the scotomas were not expected to obscure pedestrian hazards, gaze tracking revealed that scotomas did sometimes interfere with detection; late reactions usually occurred when pedestrians were entirely or partially obscured by the scotoma (time obscured correlated with reaction times, r = 0.57, p<0.001). We previously showed that scotomas lateral to the preferred retinal locus delay reaction times to a greater extent; however, taken together, the results of our studies suggest that any binocular CFL might negatively impact timely hazard detection while driving and should be a consideration when evaluating vision for driving.

  16. Synergistic action of hypoosmolarity and glutamine in inducing acute swelling of retinal glial (Müller) cells.

    PubMed

    Karl, Anett; Wurm, Antje; Pannicke, Thomas; Krügel, Katja; Obara-Michlewska, Marta; Wiedemann, Peter; Reichenbach, Andreas; Albrecht, Jan; Bringmann, Andreas

    2011-02-01

    High blood ammonia, elevated glutamine, and hyponatremia are pathogenic factors contributing to astrocytic swelling and brain edema in liver failure. We investigated the effects of hypoosmolarity, ammonia, and glutamine on the induction of glial cell swelling in freshly isolated slices of the rat retina. Glutamine, but not ammonia or hypoosmolarity per se, evoked a rapid (within one minute) swelling of retinal glial (Müller) cell bodies under hypoosmotic conditions. Under isoosmotic conditions, glutamine evoked a delayed swelling after 10 min of exposure. The effect of glutamine was concentration-dependent, with half-maximal and maximal effects at ∼ 0.1 and 0.5 mM. Glutamine in hypoosmotic solution induced a dissipation of the mitochondrial membrane potential. The effects on the mitochondrial membrane potential and the glial soma size were reduced by (i) agents which inhibit the transfer of glutamine into mitochondria and its hydrolysis there, (ii) inhibition of the mitochondrial permeability transition, (iii) inhibitors of oxidative-nitrosative stress, and (iv) inhibitors of phospholipase A(2) and cyclooxygenase. Glutamine-induced glial swelling was also prevented by ATP and adenosine, acting at adenosine A(1) receptors. The data suggest that hypoosmolarity accelerates the swelling-inducing effect of glutamine on retinal glial cells, and that swelling induction by glutamine is mediated by inducing oxidative-nitrosative stress, inflammatory lipid mediators, and mitochondrial dysfunction.

  17. Retinal remodeling.

    PubMed

    Jones, B W; Kondo, M; Terasaki, H; Lin, Y; McCall, M; Marc, R E

    2012-07-01

    Retinal photoreceptor degeneration takes many forms. Mutations in rhodopsin genes or disorders of the retinal pigment epithelium, defects in the adenosine triphosphate binding cassette transporter, ABCR gene defects, receptor tyrosine kinase defects, ciliopathies and transport defects, defects in both transducin and arrestin, defects in rod cyclic guanosine 3',5'-monophosphate phosphodiesterase, peripherin defects, defects in metabotropic glutamate receptors, synthetic enzymatic defects, defects in genes associated with signaling, and many more can all result in retinal degenerative disease like retinitis pigmentosa (RP) or RP-like disorders. Age-related macular degeneration (AMD) and AMD-like disorders are possibly due to a constellation of potential gene targets and gene/gene interactions, while other defects result in diabetic retinopathy or glaucoma. However, all of these insults as well as traumatic insults to the retina result in retinal remodeling. Retinal remodeling is a universal finding subsequent to retinal degenerative disease that results in deafferentation of the neural retina from photoreceptor input as downstream neuronal elements respond to loss of input with negative plasticity. This negative plasticity is not passive in the face of photoreceptor degeneration, with a phased revision of retinal structure and function found at the molecular, synaptic, cell, and tissue levels involving all cell classes in the retina, including neurons and glia. Retinal remodeling has direct implications for the rescue of vision loss through bionic or biological approaches, as circuit revision in the retina corrupts any potential surrogate photoreceptor input to a remnant neural retina. However, there are a number of potential opportunities for intervention that are revealed through the study of retinal remodeling, including therapies that are designed to slow down photoreceptor loss, interventions that are designed to limit or arrest remodeling events, and

  18. Central effect of histamine in a rat model of acute trigeminal pain.

    PubMed

    Tamaddonfard, Esmaeal; Khalilzadeh, Emad; Hamzeh-Gooshchi, Nasrin; Seiednejhad-Yamchi, Sona

    2008-01-01

    In conscious rats implanted with an intracerebroventricular (icv) cannula, effect of icv injections of histamine, chlorpheniramine (H(1)-receptor antagonist) and ranitidine (H(2)-receptor blocker) was investigated in a rat model of acute trigeminal pain. Acute trigeminal pain was induced by putting a drop of 5 M NaCl solution on the corneal surface of the eye and the numbers of eye wipes were counted during the first 30 s. Histamine (20, 40 microg) and chlorpheniramine (80 microg) significantly decreased the numbers of eye wipes. Ranitidine alone had no effect. Pretreatment with chlorpheniramine did not change the histamine-induced analgesia, whereas the histamine effect on pain was inhibited with ranitidine pretreatment. These results indicate that the brain histamine, through central H(2) receptors, may be involved in the modulation of the acute trigeminal pain in rats.

  19. Infectious etiologies of acute febrile illness among patients seeking health care in south-central Cambodia.

    PubMed

    Kasper, Matthew R; Blair, Patrick J; Touch, Sok; Sokhal, Buth; Yasuda, Chadwick Y; Williams, Maya; Richards, Allen L; Burgess, Timothy H; Wierzba, Thomas F; Putnam, Shannon D

    2012-02-01

    The agents of human febrile illness can vary by region and country suggesting that diagnosis, treatment, and control programs need to be based on a methodical evaluation of area-specific etiologies. From December 2006 to December 2009, 9,997 individuals presenting with acute febrile illness at nine health care clinics in south-central Cambodia were enrolled in a study to elucidate the etiologies. Upon enrollment, respiratory specimens, whole blood, and serum were collected. Testing was performed for viral, bacterial, and parasitic pathogens. Etiologies were identified in 38.0% of patients. Influenza was the most frequent pathogen, followed by dengue, malaria, and bacterial pathogens isolated from blood culture. In addition, 3.5% of enrolled patients were infected with more than one pathogen. Our data provide the first systematic assessment of the etiologies of acute febrile illness in south-central Cambodia. Data from syndromic-based surveillance studies can help guide public health responses in developing nations.

  20. Evaluation of Retinal Nerve Fiber Layer Thickness and Axonal Transport 1 and 2 Weeks After 8 Hours of Acute Intraocular Pressure Elevation in Rats

    PubMed Central

    Abbott, Carla J.; Choe, Tiffany E.; Lusardi, Theresa A.; Burgoyne, Claude F.; Wang, Lin; Fortune, Brad

    2014-01-01

    Purpose. To compare in vivo retinal nerve fiber layer thickness (RNFLT) and axonal transport at 1 and 2 weeks after an 8-hour acute IOP elevation in rats. Methods. Forty-seven adult male Brown Norway rats were used. Procedures were performed under anesthesia. The IOP was manometrically elevated to 50 mm Hg or held at 15 mm Hg (sham) for 8 hours unilaterally. The RNFLT was measured by spectral-domain optical coherence tomography. Anterograde and retrograde axonal transport was assessed from confocal scanning laser ophthalmoscopy imaging 24 hours after bilateral injections of 2 μL 1% cholera toxin B-subunit conjugated to AlexaFluor 488 into the vitreous or superior colliculi, respectively. Retinal ganglion cell (RGC) and microglial densities were determined using antibodies against Brn3a and Iba-1. Results. The RNFLT in experimental eyes increased from baseline by 11% at 1 day (P < 0.001), peaked at 19% at 1 week (P < 0.0001), remained 11% thicker at 2 weeks (P < 0.001), recovered at 3 weeks (P > 0.05), and showed no sign of thinning at 6 weeks (P > 0.05). There was no disruption of anterograde transport at 1 week (superior colliculi fluorescence intensity, 75.3 ± 7.9 arbitrary units [AU] for the experimental eyes and 77.1 ± 6.7 AU for the control eyes) (P = 0.438) or 2 weeks (P = 0.188). There was no obstruction of retrograde transport at 1 week (RCG density, 1651 ± 153 per mm2 for the experimental eyes and 1615 ± 135 per mm2 for the control eyes) (P = 0.63) or 2 weeks (P = 0.25). There was no loss of Brn3a-positive RGC density at 6 weeks (P = 0.74) and no increase in microglial density (P = 0.92). Conclusions. Acute IOP elevation to 50 mm Hg for 8 hours does not cause a persisting axonal transport deficit at 1 or 2 weeks or a detectable RNFLT or RGC loss by 6 weeks but does lead to transient RNFL thickening that resolves by 3 weeks. PMID:24398096

  1. Molecular Diagnostic Testing by eyeGENE: Analysis of Patients With Hereditary Retinal Dystrophy Phenotypes Involving Central Vision Loss

    PubMed Central

    Alapati, Akhila; Goetz, Kerry; Suk, John; Navani, Mili; Al-Tarouti, Amani; Jayasundera, Thiran; Tumminia, Santa J.; Lee, Pauline; Ayyagari, Radha

    2014-01-01

    Purpose. To analyze the genetic test results of probands referred to eyeGENE with a diagnosis of hereditary maculopathy. Methods. Patients with Best macular dystrophy (BMD), Doyne honeycomb retinal dystrophy (DHRD), Sorsby fundus dystrophy (SFD), or late-onset retinal degeneration (LORD) were screened for mutations in BEST1, EFEMP1, TIMP3, and CTRP5, respectively. Patients with pattern dystrophy (PD) were screened for mutations in PRPH2, BEST1, ELOVL4, CTRP5, and ABCA4; patients with cone-rod dystrophy (CRD) were screened for mutations in CRX, ABCA4, PRPH2, ELOVL4, and the c.2513G>A p.Arg838His variant in GUCY2D. Mutation analysis was performed by dideoxy sequencing. Impact of novel variants was evaluated using the computational tool PolyPhen. Results. Among the 213 unrelated patients, 38 had BMD, 26 DHRD, 74 PD, 8 SFD, 6 LORD, and 54 CRD; six had both PD and BMD, and one had no specific clinical diagnosis. BEST1 variants were identified in 25 BMD patients, five with novel variants of unknown significance (VUS). Among the five patients with VUS, one was diagnosed with both BMD and PD. A novel EFEMP1 variant was identified in one DHRD patient. TIMP3 novel variants were found in two SFD patients, PRPH2 variants in 14 PD patients, ABCA4 variants in four PD patients, and p.Arg838His GUCY2D mutation in six patients diagnosed with dominant CRD; one patient additionally had a CRX VUS. ABCA4 mutations were identified in 15 patients with recessive CRD. Conclusions. Of the 213 samples, 55 patients (26%) had known causative mutations, and 13 (6%) patients had a VUS that was possibly pathogenic. Overall, selective screening for mutations in BEST1, PRPH2, and ABCA4 would likely yield the highest success rate in identifying the genetic basis for macular dystrophy phenotypes. Because of the overlap in phenotypes between BMD and PD, it would be beneficial to screen genes associated with both diseases. PMID:25082885

  2. Retinal Prosthesis

    PubMed Central

    Weiland, James D.; Humayun, Mark S.

    2015-01-01

    Retinal prosthesis have been translated from the laboratory to the clinical over the past two decades. Currently, two devices have regulatory approval for the treatment of retinitis pigmentosa. These devices provide partial sight restoration and patients use this improved vision in their everyday lives. Improved mobility and object detection are some of the more notable findings from the clinical trials. However, significant vision restoration will require both better technology and improved understanding of the interaction between electrical stimulation and the retina. This paper reviews the recent clinical trials, highlights technology breakthroughs that will contribute to next generation of retinal prostheses. PMID:24710817

  3. Retinal Detachment

    MedlinePlus

    ... immediately. Treatment How is retinal detachment treated? Small holes and tears are treated with laser surgery or ... laser surgery tiny burns are made around the hole to “weld” the retina back into place. Cryopexy ...

  4. Comparison of Serum Cortisol and Testosterone Levels in Acute and Chronic Central Serous Chorioretinopathy

    PubMed Central

    Natung, Tanie

    2015-01-01

    Purpose To compare the levels of serum cortisol and testosterone in acute and chronic central serous chorio-retinopathy (CSC). Methods Serum cortisol and testosterone levels in 30 patients with either acute or chronic CSC were evaluated using chemiluminescent immunoassay. Results The mean age was 42.43 ± 6.37 years (range, 32 to 56 years). The mean 8:00 to 9.00 a.m. serum cortisol level was 12.61 ± 4.74 µg/dL (range, 6.58 to 27.42 µg/dL). The mean serum testosterone level was 5.88 ± 1.57 ng/dL (range, 2.81 to 9.94 ng/dL). The mean visual acuity was 20 / 65.07 ± 40.56 (range, 20 / 25 to 20 / 200). There was no statistically significant difference in the mean levels of serum cortisol and testosterone between the acute and chronic cases (p > 0.05), but there was a statistically significant difference in the mean presenting visual acuity in the two groups (p < 0.05). Conclusions All except one patient in the acute group had normal levels of serum cortisol. Testosterone levels were within the normal range in both the acute and chronic cases of CSC. There is unlikely to be any statistically significant difference in the mean levels of serum cortisol and testosterone between the acute and chronic cases, but there may be a statistically significant difference in the mean presenting visual acuity in these groups. PMID:26635454

  5. Functional biomarkers for the acute effects of alcohol on the central nervous system in healthy volunteers

    PubMed Central

    Zoethout, Remco W M; Delgado, Wilson L; Ippel, Annelies E; Dahan, Albert; van Gerven, Joop M A

    2011-01-01

    The central nervous system (CNS) effects of acute alcohol administration have been frequently assessed. Such studies often use a wide range of methods to study each of these effects. Unfortunately, the sensitivity of these tests has not completely been ascertained. A literature search was performed to recognize the most useful tests (or biomarkers) for identifying the acute CNS effects of alcohol in healthy volunteers. All tests were grouped in clusters and functional domains. Afterwards, the effect of alcohol administration on these tests was scored as improvement, impairment or as no effect. Furthermore, dose–response relationships were established. A total number of 218 studies, describing 342 different tests (or test variants) were evaluated. Alcohol affected a wide range of CNS domains. Divided attention, focused attention, visuo-motor control and scales of feeling high and of subjective drug effects were identified as the most sensitive functional biomarkers for the acute CNS effects of alcohol. The large number of CNS tests that are used to determine the effects of alcohol interferes with the identification of the most sensitive ones and of drug–response relationships. Our results may be helpful in selecting rational biomarkers for studies investigating the acute CNS effects of alcohol or for future alcohol- interaction studies. PMID:21284693

  6. Bird eyes distinguish summer from winter: Retinal response to acute photoperiod change in the night-migratory redheaded bunting.

    PubMed

    Majumdar, Gaurav; Yadav, Garima; Rani, Sangeeta; Kumar, Vinod

    2015-10-01

    Eyes are the part of the circadian timekeeping system but not involved in the photoperiod regulated seasonal physiology in songbirds. Here, two experiments tested whether eyes detect and respond to seasonal change in the photoperiod environment, by examining gene and protein expressions in the retinas of redheaded buntings exposed to a single long day (LD, 16L:8D), with controls on short days (SD, 8L:16D). In the first experiment, mRNA expression of genes implicated in the light perception (opsins, rhodopsin, neuropsin, melanopsin, peropsin) and photoperiod induction (eya3, tsh-β, dio2, dio3) was measured at hours 15 and 19 (hour 0 = light on) on the first long day. There was a significant increase in the eya3, tsh-β and dio2 mRNA expression, albeit with a temporal difference, and decrease in the neuropsin mRNA expression in buntings on the first long day. There was no change in the dio3, rhodopsin, melanopsin and peropsin mRNA expressions on exposure to long days. The second experiment immunohistochemically examined the eya3, tsh-β and rhodopsin peptide expressions. eya3 was expressed in both light conditions, but with a significant higher levels in the retinal photoreceptor layer (PRL) under LD, as compared to SD. Similarly, tsh-β was expressed in the PRL of LD retinas only. Rhodopsin levels were not significantly different between SD and LD conditions, however. These results for the first time show photoperiod-dependent molecular switches in the bunting retina, similar to the well documented thyroid hormone response genes based molecular cascades in the avian hypothalamus.

  7. A Validated System for Centralized Grading of Retinopathy of Prematurity: Telemedicine Approaches to Evaluating Acute Phase ROP (e-ROP) Study

    PubMed Central

    Daniel, Ebenezer; Quinn, Graham E.; Hildebrand, P. Lloyd; Ells, Anna; Hubbard, Baker; Capone, Antonio; Martin, Revell W.; Ostroff, Candace P.; Smith, Eli; Pistilli, Maxwell; Ying, Gui-Shuang

    2016-01-01

    Importance Measurable competence derived from comprehensive and advanced training in grading digital images is critical in studies using a Reading Center to evaluate retinal fundus images from infants at risk for Retinopathy of Prematurity (ROP). Details of certification for non-physician Trained Readers (TR) have not yet been described. Objective Describe a centralized system for grading ROP digital images by TRs in the “Telemedicine Approaches to evaluating acute-phase Retinopathy of Prematurity (e-ROP) Study”. Design Multi-center observational cohort study. Setting TRs were trained by experienced ROP specialists and certified to detect ROP morphology in digital retinal images under supervision of an ophthalmologist Reading Center Director (RCD). An ROP Reading Center was developed with standard hardware, secure Internet access and customized image viewing software with an electronic grading form. A detailed protocol for grading was developed. Based on results of TR gradings, a computerized algorithm determined whether Referral-Warranted ROP (RW-ROP, defined as presence of plus disease, zone I ROP, and stage 3 or worse ROP) was present. Independent double grading was done by the TRs with adjudication of discrepant fields performed by the RCD. Participants Infants with birth weights <1251g. Interventions/Exposures Digital retinal images Main Outcome Measure(s) Intra- and inter-grader variability, and monitoring for temporal drift. Results Four TRs underwent rigorous training and certification. 5,520 image sets were double graded with 25% requiring adjudication for at least one component of RW-ROP. The weighted kappas for inter-grader agreement (N= 80 image sets) were 0.72 (0.52 – 0.93) for RW-ROP, 0.57(95% CI: 0.37 – 0.77) for plus disease, 0.43 (0.24 – 0.63) for zone I ROP and 0.67(0.47 – 0.88) for Stage 3 or worse ROP. The weighted kappa for grade re-grade agreement were 0.77(0.57 – 0.97) for RW- ROP, 0.87(0.67 – 1.00) for plus disease, 0

  8. [Autochthonous acute viral and bacterial infections of the central nervous system (meningitis and encephalitis)].

    PubMed

    Pérez-Ruiz, Mercedes; Vicente, Diego; Navarro-Marí, José María

    2008-07-01

    Rapid diagnosis of acute viral and bacterial infections of the central nervous system (meningitis and encephalitis) is highly important for the clinical management of the patient and helps to establish early therapy that may solve life-threatening situations, to avoid unnecessary empirical treatments, to reduce hospital stay, and to facilitate appropriate interventions in the context of public health. Molecular techniques, especially real-time polymerase chain reaction, have become the fastest and most sensitive diagnostic procedures for autochthonous viral meningitis and encephalitis, and their role is becoming increasingly important for the diagnosis and control of most frequent acute bacterial meningitides. Automatic and closed systems may encourage the widespread and systematic use of molecular techniques for the diagnosis of these neurological syndromes in most laboratories.

  9. The acute effects of smokeless tobacco on central aortic blood pressure and wave reflection characteristics

    PubMed Central

    Martin, Jeffrey S; Beck, Darren T; Gurovich, Alvaro N; Braith, Randy W

    2010-01-01

    The main objectives of this study were to examine the acute effect of a single dose of smokeless tobacco (ST) on central aortic blood pressure and wave reflection characteristics. Fifteen apparently healthy male subjects (aged 30.6 ± 6.2 y) were given a 2.5 g oral dose of ST after baseline measurements were recorded. Pulse wave analysis using radial artery applanation tonometry was performed in triplicate at baseline (0 min) and at 10-min intervals during (10, 20 and 30 min) and after (40, 50 and 60 min) ST use. An acute dose of ST was associated with a significant increase in heart rate (HR), central aortic systolic and diastolic blood pressure, peripheral brachial systolic and diastolic blood pressure, and aortic augmentation index normalized to a fixed heart rate of 75 bpm (AIx@75). Furthermore, ejection duration and round trip travel time of the reflected pressure wave (Δtp) were significantly decreased as a result of one time ST use. As a result of changes in aortic pressure wave reflection characteristics, there was a significant increase in wasted left ventricular pressure energy (LVEw) and the tension–time index (TTI) as a result of ST use. In conclusion, one time use of ST elicits significant transient increases in HR, central aortic pressures, AIx@75, the TTI and LVEw. Chronic users subjected to decades of elevated central pressures and left ventricular work may have an increased cardiovascular risk as central aortic pressures are even more strongly related to cardiovascular outcomes than peripheral blood pressures. PMID:20719817

  10. The acute effects of smokeless tobacco on central aortic blood pressure and wave reflection characteristics.

    PubMed

    Martin, Jeffrey S; Beck, Darren T; Gurovich, Alvaro N; Braith, Randy W

    2010-10-01

    The main objectives of this study were to examine the acute effect of a single dose of smokeless tobacco (ST) on central aortic blood pressure and wave reflection characteristics. Fifteen apparently healthy male subjects (aged 30.6 ± 6.2 y) were given a 2.5 g oral dose of ST after baseline measurements were recorded. Pulse wave analysis using radial artery applanation tonometry was performed in triplicate at baseline (0 min) and at 10-min intervals during (10, 20 and 30 min) and after (40, 50 and 60 min) ST use. An acute dose of ST was associated with a significant increase in heart rate (HR), central aortic systolic and diastolic blood pressure, peripheral brachial systolic and diastolic blood pressure, and aortic augmentation index normalized to a fixed heart rate of 75 bpm (AIx@75). Furthermore, ejection duration and round trip travel time of the reflected pressure wave (Δt(p)) were significantly decreased as a result of one time ST use. As a result of changes in aortic pressure wave reflection characteristics, there was a significant increase in wasted left ventricular pressure energy (LVE(w)) and the tension-time index (TTI) as a result of ST use. In conclusion, one time use of ST elicits significant transient increases in HR, central aortic pressures, AIx@75, the TTI and LVE(w). Chronic users subjected to decades of elevated central pressures and left ventricular work may have an increased cardiovascular risk as central aortic pressures are even more strongly related to cardiovascular outcomes than peripheral blood pressures.

  11. Retinal abnormalities in β-thalassemia major

    PubMed Central

    Bhoiwala, Devang L.; Dunaief, Joshua L.

    2015-01-01

    Patients with beta (β)-thalassemia (β-TM: thalassemia major, β-TI: thalassemia intermedia) have a variety of complications that may affect all organs, including the eye. Ocular abnormalities include retinal pigment epithelium degeneration, angioid streaks, venous tortuosity, night blindness, visual field defects, decreased visual acuity, color vision abnormalities, and acute visual loss. Patients with β-TM are transfusion dependent and require iron chelation therapy (ICT) in order to survive. Retinal degeneration may result from either retinal iron accumulation from transfusion-induced iron overload or retinal toxicity induced by ICT. Some who were never treated with ICT exhibited retinopathy, and others receiving ICT had chelator-induced retinopathy. We will focus on retinal abnormalities present in individuals with β-TM viewed in light of new findings on the mechanisms and manifestations of retinal iron toxicity. PMID:26325202

  12. Retine revisited.

    PubMed

    Douglas, D E

    2002-10-01

    Retine, so named by Albert Szent-Györgyi, an inhibitor of the growth of transplanted malignant tumours in animals, is present in all mammalian tissues and in urine. Its inhibitory activity was extensively investigated by Szent-Györgyi, but its exact chemical identity was not determined. Details of the reported physical and chemical properties of retine and its ubiquitous occurrence identify it as being identical to a complex mixture of lipid 2,4-diketones of similar ubiquitous occurrence. This lipid mixture has been extensively studied, and individual members have been synthesized.

  13. Effect of acute stress on sexual behavior in female rats: participation of the central angiotensinergic system.

    PubMed

    Cecconello, Ana Lúcia; Raineki, Charlis; Sebben, Vanise; Lucion, Aldo Bolten; Sanvitto, Gilberto Luiz

    2010-03-05

    Stress might influence the reproductive behavior in females, and central angiotensin II (Ang II) is a peptide that plays a role in stress response and in the modulation of sexual behavior. The medial amygdala (MeA), an important structure that regulates this behavior, is strongly involved in stress response. The aim of the present study was to evaluate the effect of acute restraint stress on the night of proestrus on sexual receptivity in female rats and the participation of Ang II and MeA in this effect. Adult female Wistar rats with regular estrous cycles were utilized. The acute stress protocol utilized was the restraint stress for 15 min on the night of proestrus. The participation of Ang II was evaluated by injecting Ang II and Ang II receptor antagonists (losartan and PD12319) into the MeA. The lordosis quotient was recorded. The stress or the microinjection of Ang II into the MeA significantly reduced sexual behavior. The blockade of AT(1) or AT(2) receptors in the MeA prevented the effect of stress and the effect of Ang II microinjection into this nucleus on sexual receptivity. We concluded that acute restraint stress on the night of proestrus reduces sexual behavior in rats, and this effect is mediated by both AT(1) and AT(2) receptors in the MeA.

  14. Central nervous insulin administration does not potentiate the acute glucoregulatory impact of concurrent mild hyperinsulinemia.

    PubMed

    Ott, Volker; Lehnert, Hendrik; Staub, Josefine; Wönne, Kathrin; Born, Jan; Hallschmid, Manfred

    2015-03-01

    Experiments in rodents suggest that hypothalamic insulin signaling essentially contributes to the acute control of peripheral glucose homeostasis. Against this background, we investigated in healthy humans whether intranasal (IN) insulin, which is known to effectively reach the brain compartment, impacts systemic glucose metabolism. Twenty overnight-fasted healthy, normal-weight men were IN administered 210 and 420 international units [IU] (10 and 20 IU every 15 min) of the insulin analog aspart (ins-asp) and placebo, respectively, during experimental sessions lasting 6 h. The use of ins-asp rather than human insulin enabled us to disentangle exogenous and endogenous insulin kinetics. IN insulin dose-dependently decreased plasma glucose concentrations while reducing C-peptide and attenuating endogenous insulin levels. However, we also observed a slight dose-dependent permeation of ins-asp into the circulation. In control experiments mimicking the systemic but not the central nervous uptake of the IN 210 IU dose via intravenous infusion of ins-asp at a dose of 0.12 IU/kg/24 h (n = 10), we obtained essentially identical effects on fasting plasma glucose concentrations. This pattern indicates that sustained IN insulin administration to the human brain to enhance central nervous insulin signaling does not acutely alter systemic glucose homeostasis beyond effects accounted for by concurrent mild hyperinsulinemia.

  15. Acute Papillitis in Young Female with Toxoplasmosis

    PubMed Central

    Alipanahi, Rakhshandeh; Sayyahmelli, Sima

    2011-01-01

    Papillitis and complicating acute toxoplasma retinochoroiditis, are unusual and atypical features of toxoplasmosis. This report presents a female with unusual acute papillitis. This patient had an active toxoplasmic chorioretinitis lesion that appeared to involve the optic nerve head and a major blood vessel as well as central nervous systems (CNS). Papillitis may be secondary to juxtapapillary retinitis (Jensen choroiditis). Very rarely, the optic nerve head may be the primary site of involvement. This case report illustrates a rare presentation of acute papillitis in a young immunocompetent female. PMID:21887084

  16. Retinal Vascular Changes are a Marker for Cerebral Vascular Diseases.

    PubMed

    Moss, Heather E

    2015-07-01

    The retinal circulation is a potential marker of cerebral vascular disease because it shares origin and drainage with the intracranial circulation and because it can be directly visualized using ophthalmoscopy. Cross-sectional and cohort studies have demonstrated associations between chronic retinal and cerebral vascular disease, acute retinal and cerebral vascular disease, and chronic retinal vascular disease and acute cerebral vascular disease. In particular, certain qualitative features of retinopathy, retinal artery occlusion, and increased retinal vein caliber are associated with concurrent and future cerebrovascular events. These associations persist after accounting for confounding variables known to be disease-causing in both circulations, which supports the potential use of retinal vasculature findings to stratify individuals with regards to cerebral vascular disease risk.

  17. Microsystems Technology for Retinal Implants

    NASA Astrophysics Data System (ADS)

    Weiland, James

    2005-03-01

    The retinal prosthesis is targeted to treat age-related macular degeneration, retinitis pigmentosa, and other outer retinal degenerations. Simulations of artificial vision have predicted that 600-1000 individual pixels will be needed if a retinal prosthesis is to restore function such as reading large print and face recognition. An implantable device with this many electrode contacts will require microsystems technology as part of its design. An implantable retinal prosthesis will consist of several subsystems including an electrode array and hermetic packaging. Microsystems and microtechnology approaches are being investigated as possible solutions for these design problems. Flexible polydimethylsiloxane (PDMS) substrate electrode arrays and silicon micromachined electrode arrays are under development. Inactive PDMS electrodes have been implanted in 3 dogs to assess mechanical biocompatibility. 3 dogs were followed for 6 months. The implanted was securely fastened to the retina with a single retinal tack. No post-operative complications were evident. The array remained within 100 microns of the retinal surface. Histological evaluation showed a well preserved retina underneath the electrode array. A silicon device with electrodes suspended on micromachined springs has been implanted in 4 dogs (2 acute implants, 2 chronic implants). The device, though large, could be inserted into the eye and positioned on the retina. Histological analysis of the retina from the spring electrode implants showed that spring mounted posts penetrated the retina, thus the device will be redesigned to reduce the strength of the springs. These initial implants will provide information for the designers to make the next generation silicon device. We conclude that microsystems technology has the potential to make possible a retinal prosthesis with 1000 individual contacts in close proximity to the retina.

  18. A Randomized Trial Comparing the Efficacy and Safety of Intravitreal Triamcinolone With Observation to Treat Vision Loss Associated With Macular Edema Secondary to Central Retinal Vein Occlusion

    PubMed Central

    Ip, Michael S.; Scott, Ingrid U.; VanVeldhuisen, Paul C.; Oden, Neal L.; Blodi, Barbara A.; Fisher, Marian; Singerman, Lawrence J.; Tolentino, Michael; Chan, Clement K.; Gonzalez, Victor H.

    2009-01-01

    Objective: To compare the efficacy and safety of 1-mg and 4-mg doses of preservative-free intravitreal triamcinolone with observation for eyes with vision loss associated with macular edema secondary to perfused central retinal vein occlusion (CRVO). Methods: Multicenter, randomized, clinical trial of 271 participants. Main Outcome Measure: Gain in visual acuity letter score of 15 or more from baseline to month 12. Results: Seven percent, 27%, and 26% of participants achieved the primary outcome in the observation, 1-mg, and 4-mg groups, respectively. The odds of achieving the primary outcome were 5.0 times greater in the 1-mg group than the observation group (odds ratio [OR],5.0; 95% confidence interval [CI], 1.8-14.1; P=.001) and 5.0 times greater in 4-mg group than the observation group (OR,5.0; 95% CI, 1.8-14.4; P=.001); there was no difference identified between the 1-mg and 4-mg groups (OR, 1.0; 95% CI, 0.5-2.1; P=.97). The rates of elevated intraocular pressure and cataract were similar for the observation and 1-mg groups, but higher in the 4-mg group. Conclusions: Intravitreal triamcinolone is superior to observation for treating vision loss associated with macular edema secondary to CRVO in patients who have characteristics similar to those in the SCORE-CRVO trial. The 1-mg dose has a safety profile superior to that of the 4-mg dose. Application to Clinical Practice: Intravitreal triamcinolone in a 1-mg dose, following the retreatment criteria applied in the SCORE Study, should be considered for up to 1 year, and possibly 2 years, for patients with characteristics similar to those in the SCORE-CRVO trial. Trial Registration: clinicaltrials.gov Identifier: NCT00105027 PMID:19752419

  19. Poliomyelitis: immunoglobulin-containing cells in the central nervous system in acute and convalescent phases of the human disease.

    PubMed Central

    Esiri, M M

    1980-01-01

    The immunoperoxidase method has been used to demonstrate the presence of immunoglobulin-containing cells in the central nervous system in acute and convalescent phases of poliomyelitis. These cells were found in considerable numbers in the areas of damage during the acute phase, and persisted at the same sites, though in smaller numbers, during the convalescent phase for at least 8 months. Most of the positively stained cells were plasma cells. IgA was the commonest heavy chain type demonstrated, with lesser amounts also of IgG and, during the acute phase, IgM. In the acute phase more lambda than kappa light chain was demonstrated but in the convalescent phase this ratio was reversed. More light chain than heavy chain was demonstrable during the acute phase. The significance of these results is briefly discussed. Images Fig. 2 PMID:6771081

  20. Incidence and risk factors for central nervous system relapse in children and adolescents with acute lymphoblastic leukemia

    PubMed Central

    Cancela, Camila Silva Peres; Murao, Mitiko; Viana, Marcos Borato; de Oliveira, Benigna Maria

    2012-01-01

    Background Despite all the advances in the treatment of childhood acute lymphoblastic leukemia, central nervous system relapse remains an important obstacle to curing these patients. This study analyzed the incidence of central nervous system relapse and the risk factors for its occurrence in children and adolescents with acute lymphoblastic leukemia. Methods This study has a retrospective cohort design. The studied population comprised 199 children and adolescents with a diagnosis of acute lymphoblastic leukemia followed up at Hospital das Clinicas, Universidade Federal de Minas Gerais (HC-UFMG) between March 2001 and August 2009 and submitted to the Grupo Brasileiro de Tratamento de Leucemia da Infância - acute lymphoblastic leukemia (GBTLI-LLA-99) treatment protocol. Results The estimated probabilities of overall survival and event free survival at 5 years were 69.5% (± 3.6%) and 58.8% (± 4.0%), respectively. The cumulative incidence of central nervous system (isolated or combined) relapse was 11.0% at 8 years. The estimated rate of isolated central nervous system relapse at 8 years was 6.8%. In patients with a blood leukocyte count at diagnosis ≥ 50 x 109/L, the estimated rate of isolated or combined central nervous system relapse was higher than in the group with a count < 50 x 109/L (p-value = 0.0008). There was no difference in cumulative central nervous system relapse (isolated or combined) for the other analyzed variables: immunophenotype, traumatic lumbar puncture, interval between diagnosis and first lumbar puncture and place where the procedure was performed. Conclusions These results suggest that a leukocyte count > 50 x 109/L at diagnosis seems to be a significant prognostic factor for a higher incidence of central nervous system relapse in childhood acute lymphoblastic leukemia. PMID:23323068

  1. Filling in the retinal image

    NASA Technical Reports Server (NTRS)

    Larimer, James; Piantanida, Thomas

    1990-01-01

    The optics of the eye form an image on a surface at the back of the eyeball called the retina. The retina contains the photoreceptors that sample the image and convert it into a neural signal. The spacing of the photoreceptors in the retina is not uniform and varies with retinal locus. The central retinal field, called the macula, is densely packed with photoreceptors. The packing density falls off rapidly as a function of retinal eccentricity with respect to the macular region and there are regions in which there are no photoreceptors at all. The retinal regions without photoreceptors are called blind spots or scotomas. The neural transformations which convert retinal image signals into percepts fills in the gaps and regularizes the inhomogeneities of the retinal photoreceptor sampling mosaic. The filling-in mechamism plays an important role in understanding visual performance. The filling-in mechanism is not well understood. A systematic collaborative research program at the Ames Research Center and SRI in Menlo Park, California, was designed to explore this mechanism. It was shown that the perceived fields which are in fact different from the image on the retina due to filling-in, control some aspects of performance and not others. Researchers have linked these mechanisms to putative mechanisms of color coding and color constancy.

  2. Protective effect of central thyrotropin-releasing hormone analog on cerulein-induced acute pancreatitis in rats.

    PubMed

    Yoneda, Masashi; Goto, Manabu; Nakamura, Kimihide; Shimada, Tadahito; Hiraishi, Hideyuki; Terano, Akira; Haneda, Masakazu

    2005-02-15

    Central neuropeptides play a role in many physiological functions through the autonomic nervous system. We have recently demonstrated that central injection of a thyrotropin-releasing hormone (TRH) analog increases pancreatic blood flow through vagal and nitric oxide-dependent pathways. In this study, the central effect of a TRH analog on experimental acute pancreatitis was investigated in rats. Acute pancreatitis was induced by two intraperitoneal injections of cerulein (40 microg/kg) at 1-h interval. Either stable TRH analog, RX 77368 (5-100 ng), or saline was injected intracisternally 15 min before the first cerulein injection under ether anesthesia. Serum amylase level was measured before and 5 h after the first cerulein injection. Pancreatic wet/dry weight ratio and histological changes were also evaluated. Intracisternal TRH analog inhibited cerulean-induced elevation of serum amylase level, increase in pancreatic wet/dry weight ratio and pancreatic histological changes, such as interstitial edema, inflammation and vacuolization. The pancreatic cytoprotection induced by central TRH analog was abolished by subdiaphragmatic vagotomy and N(G)-nitro-L-arginine-methyl ester (L-NAME), but not by 6-hydroxydopamine (6-OHDA). Intravenous administration of the TRH analog did not influence cerulein-induced acute pancreatitis. These results indicate that the TRH analog acts in the central nervous system to protect against acute pancreatitis through vagal and nitric oxide-dependent pathways.

  3. Molecular Analysis of Central Nervous System Disease Spectrum in Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Hicks, Chindo; Sitthi-Amorn, Jitsuda; Douglas, Jessica; Ramani, Ritika; Miele, Lucio; Vijayakumar, Vani; Karlson, Cynthia; Chipeta, James; Megason, Gail

    2016-01-01

    Treatment of the central nervous system (CNS) is an essential therapeutic component in childhood acute lymphoblastic leukemia (ALL). The goal of this study was to identify molecular signatures distinguishing patients with CNS disease from those without the disease in pediatric patients with ALL. We analyzed gene expression data from 207 pediatric patients with ALL. Patients without CNS were classified as CNS1, while those with mild and advanced CNS disease were classified as CNS2 and CNS3, respectively. We compared gene expression levels among the three disease classes. We identified gene signatures distinguishing the three disease classes. Pathway analysis revealed molecular networks and biological pathways dysregulated in response to CNS disease involvement. The identified pathways included the ILK, WNT, B-cell receptor, AMPK, ERK5, and JAK signaling pathways. The results demonstrate that transcription profiling could be used to stratify patients to guide therapeutic decision-making in pediatric ALL. PMID:26997880

  4. Molecular evidence for central nervous system involvement in children with newly diagnosed acute lymphoblastic leukemia.

    PubMed

    Januszkiewicz, D A; Nowak, J S

    1995-01-01

    Central nervous system (CNS) involvement in children with newly diagnosed acute lymphoblastic leukemia (ALL) would have profound implication for the prognosis and accurate stratification of CNS prophylactic therapy. Using PCR technique with specific primers for V, D and J segments of TCRD gene, the pattern of TCRD gene rearrangements in bone marrow lymphoblasts and in cells from cerebrospinal fluid (CSF) have been investigated. The study involved 21 children at the time of diagnosis with B-lineage ALL. In nine of 21 patients incomplete TCRDVD gene rearrangement has been found in CSF cells, which was identical to that observed in bone marrow of the same children. It can be concluded that at least in 43 per cent of all analysed cases, there were signs of CNS involvement in newly diagnosed ALL patients.

  5. Central autonomic network mediates cardiovascular responses to acute inflammation: Relevance to increased cardiovascular risk in depression?

    PubMed Central

    Harrison, Neil A.; Cooper, Ella; Voon, Valerie; Miles, Ken; Critchley, Hugo D.

    2013-01-01

    Inflammation is a risk factor for both depression and cardiovascular disease. Depressed mood is also a cardiovascular risk factor. To date, research into mechanisms through which inflammation impacts cardiovascular health rarely takes into account central effects on autonomic cardiovascular control, instead emphasizing direct effects of peripheral inflammatory responses on endothelial reactivity and myocardial function. However, brain responses to inflammation engage neural systems for motivational and homeostatic control and are expressed through depressed mood state and changes in autonomic cardiovascular regulation. Here we combined an inflammatory challenge, known to evoke an acute reduction in mood, with neuroimaging to identify the functional brain substrates underlying potentially detrimental changes in autonomic cardiovascular control. We first demonstrated that alterations in the balance of low to high frequency (LF/HF) changes in heart rate variability (a measure of baroreflex sensitivity) could account for some of the inflammation-evoked changes in diastolic blood pressure, indicating a central (rather than solely local endothelial) origin. Accompanying alterations in regional brain metabolism (measured using 18FDG-PET) were analysed to localise central mechanisms of inflammation-induced changes in cardiovascular state: three discrete regions previously implicated in stressor-evoked blood pressure reactivity, the dorsal anterior and posterior cingulate and pons, strongly mediated the relationship between inflammation and blood pressure. Moreover, activity changes within each region predicted the inflammation-induced shift in LF/HF balance. These data are consistent with a centrally-driven component originating within brain areas supporting stressor evoked blood pressure reactivity. Together our findings highlight mechanisms binding psychological and physiological well-being and their perturbation by peripheral inflammation. PMID:23416033

  6. [Retinal vein occlusion in a young patient].

    PubMed

    Zemba, Mihail; Ochinciuc, Uliana; Sarbu, Laura; Avram, Corina; Camburu, Raluca; Stamate, Alina

    2013-01-01

    We present a case report of a 27 years old pacient with central retinal vein occlussion and macular edema. The pacient has a significant reduction of the macular aedema with complete recovery of vision after the treatment.

  7. Evidence Report: Risk of Acute and Late Central Nervous System Effects from Radiation Exposure

    NASA Technical Reports Server (NTRS)

    Nelson, Gregory A.; Simonsen, Lisa; Huff, Janice L.

    2016-01-01

    Possible acute and late risks to the central nervous system (CNS) from galactic cosmic rays (GCR) and solar particle events (SPE) are concerns for human exploration of space. Acute CNS risks may include: altered cognitive function, reduced motor function, and behavioral changes, all of which may affect performance and human health. Late CNS risks may include neurological disorders such as Alzheimer's disease (AD), dementia and premature aging. Although detrimental CNS changes are observed in humans treated with high-dose radiation (e.g., gamma rays and 9 protons) for cancer and are supported by experimental evidence showing neurocognitive and behavioral effects in animal models, the significance of these results on the morbidity to astronauts has not been elucidated. There is a lack of human epidemiology data on which to base CNS risk estimates; therefore, risk projection based on scaling to human data, as done for cancer risk, is not possible for CNS risks. Research specific to the spaceflight environment using animal and cell models must be compiled to quantify the magnitude of CNS changes in order to estimate this risk and to establish validity of the current permissible exposure limits (PELs). In addition, the impact of radiation exposure in combination with individual sensitivity or other space flight factors, as well as assessment of the need for biological/pharmaceutical countermeasures, will be considered after further definition of CNS risk occurs.

  8. Evaluation of the acute cardiac and central nervous system effects of the fluorocarbon trifluoromethane in baboons

    SciTech Connect

    Branch, C.A.; Goldberg, D.A.; Ewing, J.R.; Butt, S.S.; Gayner, J.; Fagan, S.C.

    1994-12-31

    The gaseous fluorocarbon trifluoromethane has recently been investigated for its potential as an in vivo gaseous indicator for nuclear magnetic resonance studies of brain perfusion. Trifluoromethane may also have significant value as a replacement for chlorofluorocarbon fire retardants. Because of possible species-specific cardiotoxic and anesthetic properties, the toxicological evaluation of trifluoromethane in primates (Papio anubis) is necessary prior to its evaluation in humans. We report the acute cardiac and central nervous system effects of trifluoromethane in eight anesthetized baboons. A dose-response effect was established for respiratory rate, electroencephalogram, and cardiac sinus rate, which exhibited a stepwise decrease from 10% trifluoromethane. No spontaneous arrhythmias were noted, and arterial blood pressure remained unchanged at any inspired level. Intravenous epinephrine infusions (1 {mu}g/kg) induced transient cardiac arrhythmia in 1 animal only at 70% FC-23 (v/v) trifluoromethane. Trifluoromethane appears to induce mild dose-related physiological changes at inspired levels of 30% or more, indicative of an anesthetic effect. These data suggest that trifluoromethane may be safe to use in humans, without significant adverse acute effects, at an inspired level of 30%. 23 refs., 3 figs., 3 tabs.

  9. The effects of prophylactic treatment of the central nervous system on the intellectual functioning of children with acute lymphocytic leukemia

    SciTech Connect

    Moss, H.A.; Nannis, E.D.; Poplack, D.G.

    1981-07-01

    The effect of central nervous system prophylaxis (cranial radiation and intrathecal chemotherapy) on intellectual function was studied in 24 children with acute lymphocytic leukemia. The Wechsler Intelligence tests were administered to these children and to a sample of their healthy siblings, who served as a comparison group. The mean Full Scale lQ was 98.6 for the patients and 112.5 for the sibling controls (p less than 0.001 level). Those patients who received central nervous system preventive treatment at a young age exhibited a greater decrement in intellectual abilities than did patients who were older when they received this treatment. In contrast, leukemia patients who had not received central nervous system prophylaxis had IQs that did not differ statistically from those of their siblings. These data suggest that central nervous system prophylaxis may have an adverse effect on the intellectual capability of children with acute lymphocytic leukemia.

  10. Retinitis pigmentosa

    PubMed Central

    Hamel, Christian

    2006-01-01

    Retinitis pigmentosa (RP) is an inherited retinal dystrophy caused by the loss of photoreceptors and characterized by retinal pigment deposits visible on fundus examination. Prevalence of non syndromic RP is approximately 1/4,000. The most common form of RP is a rod-cone dystrophy, in which the first symptom is night blindness, followed by the progressive loss in the peripheral visual field in daylight, and eventually leading to blindness after several decades. Some extreme cases may have a rapid evolution over two decades or a slow progression that never leads to blindness. In some cases, the clinical presentation is a cone-rod dystrophy, in which the decrease in visual acuity predominates over the visual field loss. RP is usually non syndromic but there are also many syndromic forms, the most frequent being Usher syndrome. To date, 45 causative genes/loci have been identified in non syndromic RP (for the autosomal dominant, autosomal recessive, X-linked, and digenic forms). Clinical diagnosis is based on the presence of night blindness and peripheral visual field defects, lesions in the fundus, hypovolted electroretinogram traces, and progressive worsening of these signs. Molecular diagnosis can be made for some genes, but is not usually performed due to the tremendous genetic heterogeneity of the disease. Genetic counseling is always advised. Currently, there is no therapy that stops the evolution of the disease or restores the vision, so the visual prognosis is poor. The therapeutic approach is restricted to slowing down the degenerative process by sunlight protection and vitaminotherapy, treating the complications (cataract and macular edema), and helping patients to cope with the social and psychological impact of blindness. However, new therapeutic strategies are emerging from intensive research (gene therapy, neuroprotection, retinal prosthesis). PMID:17032466

  11. Clinical research of fenofibrate and spironolactone for acute central serous chorioretinopathy

    PubMed Central

    Chai, Yong; Liu, Rong-Qiang; Yi, Jing-Lin; Ye, Ling-Hong; Zou, Jing; Jiang, Nan; Shao, Yi

    2016-01-01

    AIM To compare the effectiveness of combined fenofibrate and spironolactone with fenofibrate alone for treatment of central serous chorioretinopathy (CSCR). METHODS Totally 60 patients (60 eyes) with a history of acute CSCR were randomed into two groups: group A with combination of fenofibrate (200 mg) and spironolactone (100 mg), and group B with only fenofibrate (200 mg). They were taken half an hour before meals and once per day for 8wk. The changes of the visual acuity, subjective symptom, ocular surface disease index (OSDI), the tear film and optical coherence tomography were observed at 2, 4, 6, and 8wk before and after treatment. RESULTS The best corrected visual acuity (BCVA, logMAR) was improved to 0.22 and 0.27 after treatment from baseline of 0.35 and 0.36 in groups A and B (P<0.05), respectively. After 8wk treatment, the central subfield thickness (CST), and subretinal fluid volumn (SFV) decreased significantly to 49.5% and 78.8% in group A and 37.0% and 57.2% in group B. There were significant differences of CST and SFV in both groups (all P<0.05). CONCLUSION Fenofibrate combined with spironolactone may have more clinical efficacy in the treatment of CSCR than fenofibrate only. PMID:27803862

  12. Neuropsychological sequelae of central nervous system prophylaxis in survivors of childhood acute lymphoblastic leukemia

    SciTech Connect

    Said, J.A.; Waters, B.G.; Cousens, P.; Stevens, M.M.

    1989-04-01

    We assessed neuropsychologically 106 children with acute lymphoblastic leukemia (ALL) who had all received cranial irradiation for the prevention of central nervous system (CNS) leukemia 1-13 years previously. Children were assessed for adverse late effects of their therapy, using age-appropriate Wechsler measures of overall intellectual ability and supplementary tests. Forty-five siblings near in age to the patients were tested as controls. The patients who had had the most intensive central nervous system (CNS) prophylaxis were found to have a WISC-R Full Scale IQ 17 points lower than the sibling control group. Performance IQ was more affected than verbal IQ. The patients were more easily distracted and less able to concentrate. The severity of the aftereffects was related to younger age at the time of CNS prophylaxis and to a higher dose of cranial irradiation but not to time since CNS prophylaxis. CNS prophylaxis using a combination of cranial irradiation and intrathecal methotrexate has lowered the incidence of CNS relapse in childhood ALL but is associated with considerable long-term morbidity in survivors.

  13. Hickman to central venous catheter: A case of difficult venous access in a child suffering from acute lymphoblastic leukemia

    PubMed Central

    Chakraborty, Arunangshu; Agrawal, Sanjit; Datta, Taniya; Mitra, Suparna; Khemka, Rakhi

    2016-01-01

    Chemotherapy in children suffering from cancer usually requires placement of an indwelling central venous catheter (CVC). A child may need to undergo repeated procedures because of infection and occlusion of previous access devices. We present a case of CVC insertion in a child suffering from acute lymphoblastic leukemia where an innovative technique was employed. PMID:27695218

  14. Is the outcome in acute aortic dissection type A influenced by of femoral versus central cannulation?

    PubMed Central

    Bucsky, Bence S.; Richardt, Doreen; Petersen, Michael; Sievers, Hans H.

    2016-01-01

    Background The purpose of this study was to evaluate the single-center experience in initial femoral versus central cannulation of the extracorporeal circulation for acute aortic dissection type A (AADA). Methods Between January 2003 and December 2015, 235 patients underwent repair of AADA. All patients were evaluated for the type of arterial cannulation (femoral vs. central) for initial bypass. Demographic data and outcome parameters were accessed. Results One hundred and twenty seven (54.0%) were initially cannulated in the central aortic vessels (ascending aorta or subclavian/axillary artery) and 108 (46.0%) in the femoral artery. Patients were comparable between age (62.4±14.4 vs. 62.9±14.4 years, P=0.805), gender (male, 62.2 vs. 69.4%, P=0.152) and previous sternotomy (15.7 vs. 16.7%, P=0.861) between both cannulation groups; while EuroSCORE I (11.5±4.0 vs. 12.7±4.2, P=0.031) and ASA Score (3.5±0.81 vs. 3.8±0.57, P=0.011) were significantly higher in the femoral artery cannulation group. Bypass (249±102 vs. 240±81 min, P=0.474), X-clamp (166±85 vs. 157±67 min, P=0.418) and circulatory arrest time (51.6±28.7 vs. 48.3±21.7 min, P=0.365) were similar between the groups as were lowest temperature (18.1±2.0 vs. 18.1±2.2, P=0.775). Postoperative neurologic deficit and 30-day mortality were comparable between both cannulation groups (11.7 vs. 7.2%, P=0.449 and 20.2 vs. 16.9%, P=0.699, central vs. peripheral cannulation). Multivariate analysis revealed only EuroScore I above 13 as single preoperative predictor for mortality. Conclusions AADA can be operated with both femoral and central cannulation with similar results. Risk for early mortality was driven by the preoperative clinical and hemodynamic status before operation rather than the cannulation technique. PMID:27563543

  15. [Study on preferred retinal locus].

    PubMed

    Dai, Bing-Fa; Hu, Jian-Min; Xu, Duan-Lian

    2012-03-01

    Preferred retinal locus (PRL) is always found in the age-related macular degeneration and other macular damages in patients with low vision, and it is a very important anatomic position in patients with central vision impairment to achieve the rehabilitation. In recent years, the training of preferred retinal locus (PRL) has become a research hotspot of low vision rehabilitation, it can clearly improve functional vision and quality of life. The authors reviewed relevant literatures, and summarized the definition, position, characteristics, training and clinical implications of the PRL.

  16. Congestive kidney failure in cardiac surgery: the relationship between central venous pressure and acute kidney injury.

    PubMed

    Gambardella, Ivancarmine; Gaudino, Mario; Ronco, Claudio; Lau, Christopher; Ivascu, Natalia; Girardi, Leonard N

    2016-11-01

    Acute kidney injury (AKI) in cardiac surgery has traditionally been linked to reduced arterial perfusion. There is ongoing evidence that central venous pressure (CVP) has a pivotal role in precipitating acute renal dysfunction in cardiac medical and surgical settings. We can regard this AKI driven by systemic venous hypertension as 'kidney congestive failure'. In the cardiac surgery population as a whole, when the CVP value reaches the threshold of 14 mmHg in postoperative period, the risk of AKI increases 2-fold with an odds ratio (OR) of 1.99, 95% confidence interval (95% CI) of 1.16-3.40. In cardiac surgery subsets where venous hypertension is a hallmark feature, the incidence of AKI is higher (tricuspid disease 30%, carcinoid valve disease 22%). Even in the non-chronically congested coronary artery bypass population, CVP measured 6 h postoperatively showed significant association to renal failure: risk-adjusted OR for AKI was 5.5 (95% CI 1.93-15.5; P = 0.001) with every 5 mmHg rise in CVP for patients with CVP <9 mmHg; for CVP increments of 5 mmHg above the threshold of 9 mmHg, the risk-adjusted OR for AKI was 1.3 (95% CI 1.01-1.65; P = 0.045). This and other clinical evidence are discussed along with the underlying pathophysiological mechanisms, involving the supremacy of volume receptors in regulating the autonomic output in hypervolaemia, and the regional effect of venous congestion on the nephron. The effect of CVP on renal function was found to be modulated by ventricular function class, aetiology and acuity of venous congestion. Evidence suggests that acute increases of CVP should be actively treated to avoid a deterioration of the renal function, particularly in patients with poor ventricular fraction. Besides, the practice of treating right heart failure with fluid loading should be avoided in favour of other ways to optimize haemodynamics in this setting, because of the detrimental effects on the kidney function.

  17. Central nervous system complications during treatment of acute lymphoblastic leukemia in a single pediatric institution.

    PubMed

    Parasole, Rosanna; Petruzziello, Fara; Menna, Giuseppe; Mangione, Argia; Cianciulli, Emilio; Buffardi, Salvatore; Marchese, Luciano; Nastro, Anna; Misuraca, Aldo; Poggi, Vincenzo

    2010-06-01

    Central nervous system (CNS) complications during treatment of childhood acute lymphoblastic leukemia (ALL) remain a challenging clinical problem. Outcome improvement with more intensive chemotherapy has significantly increased the incidence and severity of adverse events. This study analyzed the incidence of neurological complications during ALL treatment in a single pediatric institution, focusing on clinical, radiological, and electrophysiological findings. Exclusion criteria included CNS leukemic infiltration at diagnosis, therapy-related peripheral neuropathy, late-onset encephalopathy, or long-term neurocognitive defects. During a 9-year period, we retrospectively collected 27 neurological events (11%) in as many patients, from 253 children enrolled in the ALL front-line protocol. CNS complications included posterior reversible leukoencephalopathy syndrome (n = 10), stroke (n = 5), temporal lobe epilepsy (n = 2), high-dose methotrexate toxicity (n = 2), syndrome of inappropriate antidiuretic hormone secretion (n = 1), and other unclassified events (n = 7). In conclusion, CNS complications are frequent events during ALL therapy, and require rapid detection and prompt treatment to limit permanent damage.

  18. Central Nervous System Involvement in Adult Acute Lymphoblastic Leukemia: Diagnostic Tools, Prophylaxis, and Therapy

    PubMed Central

    Del Principe, Maria Ilaria; Maurillo, Luca; Buccisano, Francesco; Sconocchia, Giuseppe; Cefalo, Mariagiovanna; De Santis, Giovanna; Di Veroli, Ambra; Ditto, Concetta; Nasso, Daniela; Postorino, Massimiliano; Refrigeri, Marco; Attrotto, Cristina; Del Poeta, Giovanni; Lo-Coco, Francesco; Amadori, Sergio; Venditti, Adriano

    2014-01-01

    In adult patients with acute lymphoblastic leukemia (ALL), Central Nervous System (CNS) involvement is associated with a very poor prognosis. The diagnostic assessment of this condition relies on the use of neuroradiology, conventional cytology (CC) and flow cytometry (FCM). Among these approaches, which is the gold standard it is still a matter of debate. Neuroradiology and CC have a limited sensitivity with a higher rate of false negative results. FCM demonstrated a superior sensitivity over CC, particularly when low levels of CNS infiltrating cells are present. Although prospective studies of a large series of patients are still awaited, a positive finding by FCM appears to anticipate an adverse outcome even if CC shows no infiltration. Current strategies for adult ALL CNS-directed prophylaxis or therapy involve systemic and intrathecal chemotherapy and radiation therapy. An early and frequent intrathecal injection of cytostatic combined with systemic chemotherapy is the most effective strategy to reduce the frequency of CNS involvement. In patients with CNS overt ALL, at diagnosis or upon relapse, allogeneic hematopoietic stem cell transplantation might be considered. This review discusses risk factors, diagnostic techniques for identification of CNS infiltration and modalities of prophylaxis and therapy to manage it. PMID:25408861

  19. Cerebral salt wasting syndrome in children with acute central nervous system injury.

    PubMed

    Jiménez, Raquel; Casado-Flores, Juan; Nieto, Monserrat; García-Teresa, María Angeles

    2006-10-01

    The purpose of this investigation was to describe the causes, clinical pattern, and treatment of cerebral salt wasting syndrome in children with acute central nervous system injury. This retrospective study focused on patients120 mEq/L), and volume depletion. Fourteen patients were identified with cerebral salt wasting syndrome, 12 after a neurosurgical procedure (8 brain tumor, 4 hydrocephalus) and 2 after severe brain trauma. In 11 patients the cerebral salt wasting syndrome was diagnosed during the first 48 hours of admission. Prevalence of cerebral salt wasting syndrome in neurosurgical children was 11.3/1000 surgical procedures. The minimum sodium was 122+/-7 mEq/L, the maximum urine osmolarity 644+/-59 mOsm/kgH2O. The maximum sodium supply was 1 mEq/kg/h (range, 0.1-2.4). The mean duration of cerebral salt wasting syndrome was 6+/-5 days (range 1-9). In conclusion, cerebral salt wasting syndrome can complicate the postoperative course of children with brain injury; it is frequently present after surgery for brain tumors and hydrocephalus and in patients with severe head trauma. Close monitoring of salt and fluid balance is essential to prevent severe neurologic and hemodynamic complications.

  20. Immune reconstitution complicated by CMV retinitis in a pediatric patient who underwent haploidentical CD34+-selected hematopoietic stem cell transplant for acute lymphoblastic leukemia.

    PubMed

    Cesaro, Simone; Boaro, Maria Paola; Pillon, Marta; Calore, Elisabetta; Cermakova, Ivete; Perruccio, Katia; Mengoli, Carlo; Messina, Chiara

    2008-09-01

    We describe two episodes of CMV retinitis in a pediatric patient who underwent a CD34+ selected graft from his haploidentical father. Both recipient and donor were cytomegalovirus (CMV) seropositive. Both episodes occurred late post-grafting during a phase of complete immunological recovery with sufficient numbers of circulating CMV-specific clones. Antiviral treatment with foscarnet and ganciclovir was successful but prolonged treatment was required to prevent relapses. We hypothesize that this complication was more related to an immune reconstitution process than to an immune-deficient state post-grafting. We conclude that CMV retinitis is a late complication of HSCT that can occur despite satisfactory immune reconstitution. Usually, it is responsive to antiviral therapy. Dilated fundoscopic examination is essential both for examining patients with reduced visual acuity and for screening asymptomatic patients.

  1. Missed retinal breaks in rhegmatogenous retinal detachment

    PubMed Central

    Takkar, Brijesh; Azad, Shorya; Shashni, Adarsh; Pujari, Amar; Bhatia, Indrish; Azad, Rajvardhan

    2016-01-01

    AIM To evaluate the causes and associations of missed retinal breaks (MRBs) and posterior vitreous detachment (PVD) in patients with rhegmatogenous retinal detachment (RRD). METHODS Case sheets of patients undergoing vitreo retinal surgery for RRD at a tertiary eye care centre were evaluated retrospectively. Out of the 378 records screened, 253 were included for analysis of MRBs and 191 patients were included for analysis of PVD, depending on the inclusion criteria. Features of RRD and retinal breaks noted on examination were compared to the status of MRBs and PVD detected during surgery for possible associations. RESULTS Overall, 27% patients had MRBs. Retinal holes were commonly missed in patients with lattice degeneration while missed retinal tears were associated with presence of complete PVD. Patients operated for cataract surgery were significantly associated with MRBs (P=0.033) with the odds of missing a retinal break being 1.91 as compared to patients with natural lens. Advanced proliferative vitreo retinopathy (PVR) and retinal bullae were the most common reasons for missing a retinal break during examination. PVD was present in 52% of the cases and was wrongly assessed in 16%. Retinal bullae, pseudophakia/aphakia, myopia, and horse shoe retinal tears were strongly associated with presence of PVD. Traumatic RRDs were rarely associated with PVD. CONCLUSION Pseudophakic patients, and patients with retinal bullae or advanced PVR should be carefully screened for MRBs. Though Weiss ring is a good indicator of PVD, it may still be over diagnosed in some cases. PVD is associated with retinal bullae and pseudophakia, and inversely with traumatic RRD. PMID:27990367

  2. Acute tryptophan depletion in C57BL/6 mice does not induce central serotonin reduction or affective behavioural changes.

    PubMed

    van Donkelaar, Eva L; Blokland, Arjan; Lieben, Cindy K J; Kenis, Gunter; Ferrington, Linda; Kelly, Paul A T; Steinbusch, Harry W M; Prickaerts, Jos

    2010-01-01

    Acute tryptophan depletion is extensively used to investigate the implication of serotonin in the onset of depressive disorders. In rats, it lowers peripheral tryptophan and decreases central serotonin concentrations. We aimed to establish the rat model of acute tryptophan depletion in the mouse for potential application as serotonin challenge tool in genetic mouse models of depression. Pharmacokinetic and behavioural effects of a tryptophan-free diet were examined in Swiss and C57BL/6 mice. Peripheral amino acids were measured and central tryptophan and serotonin concentrations were compared with anxiety and depression-like behaviour in the elevated zero-maze, forced swimming test or tail suspension test. While acute tryptophan depletion resulted in a 74% reduction of the plasma ratio tryptophan to the sum of other large neutral amino acids in Swiss mice 1h after administration (2x10 ml/kg, 30 min interval), there was only a 40% reduction in C57BL/6 mice. The latter did not show anxiety in the elevated zero-maze or increased immobility in the forced swimming test or tail suspension test. A higher dose (2x20 ml/kg) with a longer interval (60 min) reduced the ratio with 68% in C57BL/6 mice, lowered hippocampal serotonin turnover and had no functional effect when tested in the elevated zero-maze and forced swimming test. These findings have important implications for the use of acute tryptophan depletion in general and in particular for its application in mice. Although in healthy mice no clear central serotonin or functional effects were observed, further research is indicated using mice with pre-existing serotonin dysfunction, as they might be more vulnerable to acute tryptophan depletion.

  3. The neuroprotective effect of hyperbaric oxygen treatment on laser-induced retinal damage in rats

    NASA Astrophysics Data System (ADS)

    Vishnevskia-Dai, Victoria; Belokopytov, Mark; Dubinsky, Galina; Nachum, Gal; Avni, Isaac; Belkin, Michael; Rosner, Mordechai

    2005-04-01

    Retinal damage induced by mechanical trauma, ischemia or laser photocoagulation increases considerably by secondary degeneration processes. The spread of damage may be ameliorated by neuroprotection that is aimed at reducing the extent of the secondary degeneration and promote healing processes. Hyperbaric oxygen (HBO) treatment consists of inspiration of oxygen at higher than one absolute atmospheric pressure. Improved neural function was observed in patients with acute brain trauma or ischemia treated with HBO. This study was designed to evaluate the neuroprotective effect of hyperbaric oxygen (HBO) on laser induced retinal damage in a rat model. Standard argon laser lesions were created in 25 pigmented rats divided into three groups: Ten rats were treated immediately after the irradiation with HBO three times during the first 24 hr followed by 12 consecutive daily treatments. Five rats received a shorter treatment regimen of 10 consecutive HBO treatments. The control group (10 rats) underwent the laser damage with no additional treatment. The retinal lesions were evaluated 20 days after the injury. All outcome measures were improved by the longer HBO treatment (P<0.01). The shorter HBO treatment was less effective, showing an increase only in nuclei density at the central area of lesion (P< 0.01). Hyperbaric oxygen seems to exert a neuroprotective effect on laser-induced retinal damage in a rat model. In the range of HBO exposures studied, longer exposure provides more neuroprotection. These results encourage further evaluation of the potential therapeutic use of hyperbaric oxygen in diseases and injuries of the retina.

  4. Role of central arginine vasopressin receptors in the analgesic effect of CDP-choline on acute and neuropathic pain.

    PubMed

    Bagdas, Deniz; Yucel-Ozboluk, Hasret; Orhan, Fulya; Kanat, Ozkan; Isbil-Buyukcoskun, Naciye; Gurun, Mine S

    2013-12-04

    Recent studies have demonstrated that arginine vasopressin (AVP) plays a crucial role in pain modulation. In addition, our previous studies have proven that centrally administered cytidine-5'-diphosphate-choline (CDP-choline; citicoline) elicits an analgesic effect in different pain models in rats. Given that CDP-choline enhances central and peripheral vasopressin levels, the present study was designed to investigate the role of central AVP receptors in the analgesic effect of CDP-choline in acute and chronic constriction injury-induced neuropathic pain models. For this purpose, rats were pretreated intracerebroventricularly with the AVP V1 or AVP V2 receptor antagonist 15 min before intracerebroventricular injection of CDP-choline or saline, and pain threshold was determined using the Randall-Selitto test. AVP V1 and AVP V2 receptor antagonist blocked the CDP-choline-induced analgesic effect either in acute or neuropathic models of pain in rats. These results suggest, for the first time, that central AVP receptors are involved in the CDP-choline-elicited analgesic effect.

  5. Oximetry: recent insights into retinal vasopathies and glaucoma.

    PubMed

    Boeckaert, J; Vandewalle, E; Stalmans, I

    2012-01-01

    This review will highlight a new technology and recent insights into measuring retinal oxygen saturation in several ophthalmic diseases. A growing body of evidence suggests that disturbances in retinal blood flow and oxygenation are related to several retinopathies and glaucoma, which can severely impair vision. The retinal oximeter may allow researchers and physicians to gain deeper insights into retinal physiology and clarify the impact of ischemia on retinal health and function. There are two commercially available systems to measure retinal oxygen saturation: the Oxymap retinal oximeter (Reykjavik, Iceland) and the Imedos Systems UG (Jena, Germany). In this review we will focus on the results obtained with Oxymap. Direct and non-invasive measurement of retinal oxygen saturation have potentially useful diagnostic and therapeutic indications in various eye diseases such as diabetic retinopathy, age-related macular degeneration, central retinal vein and artery occlusion, anterior ischemic optic neuropathy and retinopathy of prematurity. Despite several limitations, oxygen saturation assessment in the retinal vessels is a significant advancement in the understanding of ocular diseases. Nevertheless, further studies are needed to validate the use of oximetry in retinal vasopathies and glaucoma.

  6. Acute tianeptine treatment selectively modulates neuronal activation in the central nucleus of the amygdala and attenuates fear extinction.

    PubMed

    Godsil, B P; Bontempi, B; Mailliet, F; Delagrange, P; Spedding, M; Jay, T M

    2015-11-01

    Antidepressant drugs are commonly prescribed treatments for anxiety disorders, and there is growing interest in understanding how these drugs impact fear extinction because extinction learning is pivotal to successful exposure-based therapy (EBT). A key objective within this domain is understanding how antidepressants alter the activation of specific elements of the limbic-based network that governs such fear processing. Chronic treatment with the antidepressant tianeptine has been shown to reduce the acquisition of extinction learning in rats, yet the drug's acute influence on activation in prefrontal and amygdalar regions, and on extinction learning are not well understood. To assess its influence on cellular activation, rats were injected with tianeptine and Fos immunoreactivity was measured in these regions. Acute tianeptine treatment selectively altered Fos expression within subdivisions of the central nucleus of the amygdala (CEA) in a bidirectional manner that varied in relation to ongoing activation within the capsular subdivision and its prefrontal and intra-amygdalar inputs. This pattern of results suggests that the drug can conditionally modulate the activation of CEA subdivisions, which contain microcircuits strongly implicated in fear processing. The effect of acute tianeptine was also examined with respect to the acquisition, consolidation and expression of fear extinction in rats. Acute tianeptine attenuated extinction learning as well as the recall of extinction memory, which underscores that acute dosing with the drug could alter learning during EBT. Together these findings provide a new perspective for understanding the mechanism supporting tianeptine's clinical efficacy, as well as its potential influence on CEA-based learning mechanisms.

  7. Inferior retinal light exposure is more effective than superior retinal exposure in suppressing melatonin in humans

    NASA Technical Reports Server (NTRS)

    Glickman, Gena; Hanifin, John P.; Rollag, Mark D.; Wang, Jenny; Cooper, Howard; Brainard, George C.

    2003-01-01

    Illumination of different areas of the human retina elicits differences in acute light-induced suppression of melatonin. The aim of this study was to compare changes in plasma melatonin levels when light exposures of equal illuminance and equal photon dose were administered to superior, inferior, and full retinal fields. Nine healthy subjects participated in the study. Plexiglass eye shields were modified to permit selective exposure of the superior and inferior halves of the retinas of each subject. The Humphrey Visual Field Analyzer was used both to confirm intact full visual fields and to quantify exposure of upper and lower visual fields. On study nights, eyes were dilated, and subjects were exposed to patternless white light for 90 min between 0200 and 0330 under five conditions: (1) full retinal exposure at 200 lux, (2) full retinal exposure at 100 lux, (3) inferior retinal exposure at 200 lux, (4) superior retinal exposure at 200 lux, and (5) a dark-exposed control. Plasma melatonin levels were determined by radioimmunoassay. ANOVA demonstrated a significant effect of exposure condition (F = 5.91, p < 0.005). Post hoc Fisher PLSD tests showed significant (p < 0.05) melatonin suppression of both full retinal exposures as well as the inferior retinal exposure; however, superior retinal exposure was significantly less effective in suppressing melatonin. Furthermore, suppression with superior retinal exposure was not significantly different from that of the dark control condition. The results indicate that the inferior retina contributes more to the light-induced suppression of melatonin than the superior retina at the photon dosages tested in this study. Findings suggest a greater sensitivity or denser distribution of photoreceptors in the inferior retina are involved in light detection for the retinohypothalamic tract of humans.

  8. The role of the immune system in central nervous system plasticity after acute injury.

    PubMed

    Peruzzotti-Jametti, L; Donegá, M; Giusto, E; Mallucci, G; Marchetti, B; Pluchino, S

    2014-12-26

    Acute brain injuries cause rapid cell death that activates bidirectional crosstalk between the injured brain and the immune system. In the acute phase, the damaged CNS activates resident and circulating immune cells via the local and systemic release of soluble mediators. This early immune activation is necessary to confine the injured tissue and foster the clearance of cellular debris, thus bringing the inflammatory reaction to a close. In the chronic phase, a sustained immune activation has been described in many CNS disorders, and the degree of this prolonged response has variable effects on spontaneous brain regenerative processes. The challenge for treating acute CNS damage is to understand how to optimally engage and modify these immune responses, thus providing new strategies that will compensate for tissue lost to injury. Herein we have reviewed the available information regarding the role and function of the innate and adaptive immune responses in influencing CNS plasticity during the acute and chronic phases of after injury. We have examined how CNS damage evolves along the activation of main cellular and molecular pathways that are associated with intrinsic repair, neuronal functional plasticity and facilitation of tissue reorganization.

  9. An animal model to study toxicity of central nervous system therapy for childhood acute lymphoblastic leukemia: Effects on behavior

    SciTech Connect

    Mullenix, P.J.; Kernan, W.J.; Tassinari, M.S.; Schunior, A.; Waber, D.P.; Howes, A.; Tarbell, N.J. )

    1990-10-15

    Central nervous system prophylactic therapy used in the treatment of acute lymphoblastic leukemia can reduce intelligence quotient scores and impair memory and attention in children. Cranial irradiation, intrathecal methotrexate, and steroids are commonly utilized in acute lymphoblastic leukemia therapy. How they induce neurotoxicity is unknown. This study employs an animal model to explore the induction of neurotoxicity. Male and female Sprague-Dawley rats at 17 and 18 days of age were administered 18 mg/kg prednisolone, 2 mg/kg methotrexate, and 1000 cGy cranial irradiation. Another 18-day-old group was administered 1000 cGy cranial irradiation but no drugs. Matching controls received saline and/or a sham exposure to radiation. All animals at 6 weeks and 4 months of age were tested for alterations in spontaneous behavior. A computer pattern recognition system automatically recorded and classified individual behavioral acts displayed during exploration of a novel environment. Measures of behavioral initiations, total time, and time structure were used to compare treated and control animals. A permanent sex-specific change in the time structure of behavior was induced by the prednisolone, methotrexate, and radiation treatment but not by radiation alone. Unlike hyperactivity, the effect consisted of abnormal clustering and dispersion of acts in a pattern indicative of disrupted development of sexually dimorphic behavior. This study demonstrates the feasibility of an animal model delineating the agent/agents responsible for the neurotoxicity of central nervous system prophylactic therapy.

  10. Diagnostic imaging in patients with retinitis pigmentosa.

    PubMed

    Mitamura, Yoshinori; Mitamura-Aizawa, Sayaka; Nagasawa, Toshihiko; Katome, Takashi; Eguchi, Hiroshi; Naito, Takeshi

    2012-01-01

    Retinitis pigmentosa (RP) is a progressive inherited retinal disease, and patients with RP have reduced visual function caused by a degeneration of the photoreceptors and retinal pigment epithelium (RPE). At the end stage of RP, the degeneration of the photoreceptors in the fovea reduces central vision, and RP is one of the main causes of acquired blindness in developed countries. Therefore, morphological and functional assessments of the photoreceptors in the macula area can be useful in estimating the residual retinal function in RP patients. Optical coherence tomography (OCT) is a well-established method of examining the retinal architecture in situ. The photoreceptor inner/outer segment (IS/OS) junction is observed as a distinct, highly reflective line by OCT. The presence of the IS/OS junction in the OCT images is essential for normal visual function. Fundus autofluorescence (FAF) results from the accumulation of lipofuscin in the RPE cells and has been used to investigate RPE and retinal function. More than one-half of RP patients have an abnormally high density parafoveal FAF ring (AF ring). The AF ring represents the border between functional and dysfunctional retina. In this review, we shall summarize recent progress on diagnostic imaging in eyes with RP.

  11. Retinal remodeling in human retinitis pigmentosa.

    PubMed

    Jones, B W; Pfeiffer, R L; Ferrell, W D; Watt, C B; Marmor, M; Marc, R E

    2016-09-01

    Retinitis Pigmentosa (RP) in the human is a progressive, currently irreversible neural degenerative disease usually caused by gene defects that disrupt the function or architecture of the photoreceptors. While RP can initially be a disease of photoreceptors, there is increasing evidence that the inner retina becomes progressively disorganized as the outer retina degenerates. These alterations have been extensively described in animal models, but remodeling in humans has not been as well characterized. This study, using computational molecular phenotyping (CMP) seeks to advance our understanding of the retinal remodeling process in humans. We describe cone mediated preservation of overall topology, retinal reprogramming in the earliest stages of the disease in retinal bipolar cells, and alterations in both small molecule and protein signatures of neurons and glia. Furthermore, while Müller glia appear to be some of the last cells left in the degenerate retina, they are also one of the first cell classes in the neural retina to respond to stress which may reveal mechanisms related to remodeling and cell death in other retinal cell classes. Also fundamentally important is the finding that retinal network topologies are altered. Our results suggest interventions that presume substantial preservation of the neural retina will likely fail in late stages of the disease. Even early intervention offers no guarantee that the interventions will be immune to progressive remodeling. Fundamental work in the biology and mechanisms of disease progression are needed to support vision rescue strategies.

  12. Genetics Home Reference: retinitis pigmentosa

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions retinitis pigmentosa retinitis pigmentosa Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Retinitis pigmentosa is a group of related eye disorders that ...

  13. Systemic viral infections and their retinal and choroidal manifestations.

    PubMed

    Yoser, S L; Forster, D J; Rao, N A

    1993-01-01

    Viruses are one of the most common causes of infections involving the posterior segment of the eye. Such infections can occur either on a congenital or an acquired basis, and may affect primarily the retina or the choroid. Congenital cytomegalovirus (CMV) and rubella infections may result in retinitis. CMV retinitis is also the most common cause of acquired viral retinitis, primarily because of the acquired immunodeficiency syndrome (AIDS). Other types of viral retinitis, such as those caused by herpes simplex or herpes zoster, can occur in immunocompromised or immunocompetent individuals. Retinitis or choroiditis caused by viruses such as measles, influenza, Epstein-Barr virus, and Rift Valley fever virus, typically occurs subsequent to an acute viral systemic illness. The systemic and ocular manifestations, as well as the histopathology, laboratory tests, differential diagnoses, and treatment regimens for each of the individual viruses are discussed in detail.

  14. Central role of neutrophil in the pathogenesis of severe acute pancreatitis

    PubMed Central

    Yang, Zhi-wen; Meng, Xiao-xiao; Xu, Ping

    2015-01-01

    Severe acute pancreatitis (SAP) is an acute abdominal disease with the strong systemic inflammatory response, and rapidly progresses from a local pancreatic damage into multiple organ dysfunction. For many decades, the contributions of neutrophils to the pathology of SAP were traditionally thought to be the chemokine and cytokine cascades that accompany inflammation. In this review, we focus mainly on those recently recognized aspects of neutrophils in SAP processes. First, emerging evidence suggests that therapeutic interventions targeting neutrophils significantly lower tissue damage and protect against the occurrence of pancreatitis. Second, trypsin activation promotes the initial neutrophils recruitment into local pancreas, and subsequently neutrophils infiltration in turn triggers trypsin production. Finally, neutrophils have the unique ability to release neutrophil extracellular traps even in the absence of pathogens. PMID:26249268

  15. Vasopressin Bolus Protocol Compared to Desmopressin (DDAVP) for Managing Acute, Postoperative Central Diabetes Insipidus and Hypovolemic Shock.

    PubMed

    Shukla, Anukrati; Alqadri, Syeda; Ausmus, Ashley; Bell, Robert; Nattanmai, Premkumar; Newey, Christopher R

    2017-01-01

    Introduction. Management of postoperative central diabetes insipidus (DI) can be challenging from changes in volume status and serum sodium levels. We report a case successfully using a dilute vasopressin bolus protocol in managing hypovolemic shock in acute, postoperative, central DI. Case Report. Patient presented after bifrontal decompressive craniotomy for severe traumatic brain injury. He developed increased urine output resulting in hypovolemia and hypernatremia. He was resuscitated with intravenous fluids including a dilute vasopressin bolus protocol. This protocol consisted of 1 unit of vasopressin in 1 liter of 0.45% normal saline. This protocol was given in boluses based on the formula: urine output minus one hundred. Initial serum sodium was 148 mmol/L, and one-hour urine output was 1 liter. After 48 hours, he transitioned to 1-desamino-8-D-arginine vasopressin (DDAVP). Pre-DDAVP serum sodium was 149 mmol/L and one-hour urine output 320 cc. Comparing the bolus protocol to the DDAVP protocol, the average sodium was 143.8 ± 3.2 and 149.6 ± 3.2 mmol/L (p = 0.0001), average urine output was 433.2 ± 354.4 and 422.3 ± 276.0 cc/hr (p = 0.90), and average specific gravity was 1.019 ± 0.009 and 1.016 ± 0.01 (p = 0.42), respectively. Conclusion. A protocol using dilute vasopressin bolus can be an alternative for managing acute, central DI postoperatively, particularly in setting of hypovolemic shock resulting in a consistent control of serum sodium.

  16. Vasopressin Bolus Protocol Compared to Desmopressin (DDAVP) for Managing Acute, Postoperative Central Diabetes Insipidus and Hypovolemic Shock

    PubMed Central

    Shukla, Anukrati; Alqadri, Syeda; Ausmus, Ashley; Bell, Robert; Nattanmai, Premkumar

    2017-01-01

    Introduction. Management of postoperative central diabetes insipidus (DI) can be challenging from changes in volume status and serum sodium levels. We report a case successfully using a dilute vasopressin bolus protocol in managing hypovolemic shock in acute, postoperative, central DI. Case Report. Patient presented after bifrontal decompressive craniotomy for severe traumatic brain injury. He developed increased urine output resulting in hypovolemia and hypernatremia. He was resuscitated with intravenous fluids including a dilute vasopressin bolus protocol. This protocol consisted of 1 unit of vasopressin in 1 liter of 0.45% normal saline. This protocol was given in boluses based on the formula: urine output minus one hundred. Initial serum sodium was 148 mmol/L, and one-hour urine output was 1 liter. After 48 hours, he transitioned to 1-desamino-8-D-arginine vasopressin (DDAVP). Pre-DDAVP serum sodium was 149 mmol/L and one-hour urine output 320 cc. Comparing the bolus protocol to the DDAVP protocol, the average sodium was 143.8 ± 3.2 and 149.6 ± 3.2 mmol/L (p = 0.0001), average urine output was 433.2 ± 354.4 and 422.3 ± 276.0 cc/hr (p = 0.90), and average specific gravity was 1.019 ± 0.009 and 1.016 ± 0.01 (p = 0.42), respectively. Conclusion. A protocol using dilute vasopressin bolus can be an alternative for managing acute, central DI postoperatively, particularly in setting of hypovolemic shock resulting in a consistent control of serum sodium. PMID:28127476

  17. Access to medicines for acute illness in middle income countries in Central America

    PubMed Central

    Emmerick, Isabel Cristina Martins; Luiza, Vera Lucia; Camacho, Luiz Antonio Bastos; Ross-Degnan, Dennis

    2013-01-01

    OBJECTIVE To analyze the main predictors of access to medicines for persons who experienced acute health conditions. METHODS This was a cross-sectional analytic study, based on data from household surveys. We examined the predictors of: (1) seeking care for acute illness in the formal health care system and (2) obtaining all medicines sought for the acute condition. RESULTS The significant predictors of seeking health care for acute illnesses were urban geographic location, head of household with secondary school education or above, age under 15, severity of illness perceived by the respondent, and having health insurance. The most important predictor of obtaining full access to medicines was seeking care in the formal health care system. People who sought care in the formal system were three times more likely to receive all the medicines sought (OR 3.0, 95%CI 2.3;4.0). For those who sought care in the formal health system, the strongest predictors of full access to medicines were seeking care in the private sector, having secondary school education or above, and positive perceptions of quality of health care and medicines in public sector health facilities. For patients who did not seek care in the formal health system, full access to medicines was more likely in Honduras or Nicaragua than in Guatemala. Urban geographic location, higher economic status, and male gender were also significant predictors. CONCLUSIONS A substantial part of the population in these three countries sought and obtained medicines outside of the formal health care system, which may compromise quality of care and pose a risk to patients. Determinants of full access to medicines inside and outside the formal health care system differ, and thus may require different strategies to improve access to medicines.  PMID:24626545

  18. Retinal detachment repair

    MedlinePlus

    Scleral buckling; Vitrectomy; Pneumatic retinopexy; Laser retinopexy; Rhegmatogenous retinal detachment repair ... it meets the hole in the retina. Scleral buckling can be done using numbing medicine while you ...

  19. Epoxygenated Fatty Acids Inhibit Retinal Vascular Inflammation

    PubMed Central

    Capozzi, Megan E.; Hammer, Sandra S.; McCollum, Gary W.; Penn, John S.

    2016-01-01

    The objective of the present study was to assess the effect of elevating epoxygenated fatty acids on retinal vascular inflammation. To stimulate inflammation we utilized TNFα, a potent pro-inflammatory mediator that is elevated in the serum and vitreous of diabetic patients. In TNFα-stimulated primary human retinal microvascular endothelial cells, total levels of epoxyeicosatrienoic acids (EETs), but not epoxydocosapentaenoic acids (EDPs), were significantly decreased. Exogenous addition of 11,12-EET or 19,20-EDP when combined with 12-(3-adamantane-1-yl-ureido)-dodecanoic acid (AUDA), an inhibitor of epoxide hydrolysis, inhibited VCAM-1 and ICAM-1 expression and protein levels; conversely the diol product of 19,20-EDP hydrolysis, 19,20-DHDP, induced VCAM1 and ICAM1 expression. 11,12-EET and 19,20-EDP also inhibited leukocyte adherence to human retinal microvascular endothelial cell monolayers and leukostasis in an acute mouse model of retinal inflammation. Our results indicate that this inhibition may be mediated through an indirect effect on NFκB activation. This is the first study demonstrating a direct comparison of EET and EDP on vascular inflammatory endpoints, and we have confirmed a comparable efficacy from each isomer, suggesting a similar mechanism of action. Taken together, these data establish that epoxygenated fatty acid elevation will inhibit early pathology related to TNFα-induced inflammation in retinal vascular diseases. PMID:27966642

  20. Acute incremental exercise, performance of a central executive task, and sympathoadrenal system and hypothalamic-pituitary-adrenal axis activity.

    PubMed

    McMorris, Terry; Davranche, Karen; Jones, Glenys; Hall, Ben; Corbett, Jo; Minter, Charles

    2009-09-01

    The purposes of this study were to examine the effect of acute incremental exercise on the performance of a central executive task; the responses of the sympathoadrenal system (SAS) and hypothalamic-pituitary-adrenal axis (HPAA) during exercise, while simultaneously carrying out the central executive task; and the ability of Delta plasma concentrations of epinephrine, norepinephrine, adrenocorticotropin hormone (ACTH) and cortisol to predict Delta performance on the central executive task. Subjects undertook a flanker task at rest and during exercise at 50% and 80% maximum aerobic power (MAP). SAS and HPAA activity were measured pre- and post-treatment by plasma concentrations of catecholamines, and cortisol and ACTH, respectively. Reaction time (RT) and number of errors for congruent and incongruent trials on the flanker task showed significant main effects with performance at 80% MAP higher than in the other conditions. RT post-correct responses were significantly faster than RT post-error at rest and 50% MAP but not at 80%. Pre- and post-treatment catecholamines showed a main effect of exercise with a linear increase. Post-treatment ACTH concentrations at 80% MAP were significantly greater than in the other conditions. Delta epinephrine and ACTH combined were significant predictors of Delta RT and Delta norepinephrine was a significant predictor of Delta number of errors. It was concluded that exercise must be at a high intensity to affect performance on the flanker task. Both the SAS and HPAA appear to play a role in the exercise-cognition interaction.

  1. Complete clinical recovery of a central pontine and extrapontine myelinolysis delayed onset in a child with acute myeloblastic leukemia.

    PubMed

    Yilmaz, D; Karapinar, B; Balkan, C; Ay, Y; Kavakli, K

    2011-02-01

    Central pontine myelinolysis (CPM) is a demyelinating disease of the pons often associated with the demyelination of extrapontine areas of the central nervous system. It typically occurs 0.5-7 days after a rapid increment in serum Na level in hyponatremic patients and may lead to death. A 2.5-year-old child with a diagnosis of acute myeloblastic leukemia developed febril neutropenia, diarrhea, gastrointestinal hemorrhage followed by pulmonary aspergillosis. He could not tolerate enteral nutrition. He was given broad spectrum antibiotics and antifungal treatment. Laboratory tests showed electrolyte abnormalities including hyponatremia, hypokalemia and hypophosphatemia in a chronic course. Twenty three days after a rapid correction of hyponatremia (16 mEq/L/24 h) he revealed flask quadriparesis, disphagia, mutism, irregular respiratory pattern and loss of cough and gag reflex. Cranial magnetic resonance showed central pontine and extrapontine myelinolysis. He required mechanical ventilation and then he regained his neurologic functions. He completed chemotherapy protocol and underwent hematopoietic stem cell transplantation. After 2.5 years of the occurrence of CPM he is in completely normal physical and neurological status. CPM is a very severe but rare disorder in children with underlying disease. In the presence of multiple etiologic factors it may reveal a delayed onset and optimum outcome can be seen even in the severe clinical presentation with adequate intensive support.

  2. Acute childhood diarrhoea and maternal time allocation in the northern central Sierra of Peru.

    PubMed

    Bentley, M E; Elder, J; Fukumoto, M; Stallings, R H; Jacoby, E; Brown, K

    1995-03-01

    Interventions to improve child health depend, at least implicitly, on changing maternal knowledge and behaviour and a reallocation of maternal time. There have been few studies, however, of the time cost involved in the adoption of new health technologies and even fewer that examine changes in maternal activities in response to child illness. The present study examines maternal daytime activities and investigates changes that occur when children are ill. We examine the impact of acute childhood diarrhoea episodes on the activity patterns of the mother/caretaker in this setting. The results show that mothers alter their usual activity patterns only slightly in response to acute diarrhoea episodes in their children. They continue to perform the same variety of activities as when the children are healthy, although they are more likely to perform them with the child 'carried' on their back. There is some indication that diarrhoea perceived to be more severe did result in the mother acting as caretaker more frequently. These findings have important implications for health interventions that depend on changing the amount of maternal or caretaker time spent for child health technologies, but the implications may vary depending on the reasons for the observed lack of changes in caretaker activities.

  3. Potential Role of Exercise in Retinal Health.

    PubMed

    Pardue, Machelle T; Chrenek, Micah A; Schmidt, Robin H; Nickerson, John M; Boatright, Jeffrey H

    2015-01-01

    For many patients suffering vision loss due to retinal degeneration, the potential exists for therapeutic intervention to halt or delay disease progression. Proposed molecular, pharmacological, and surgical treatments are expensive and complicated. Finding low-cost interventions to sustain vision and thereby quality of life is vitally important. This chapter reviews findings from animal model and human subject studies indicating that physical exercise has direct, beneficial effects on regions of the central nervous system and is protective against neurodegenerative disease, including recent data from animal models showing similar effects for retina and vision. Potential local and systemic mechanistic pathways for exercise-induced retinal neuroprotection are discussed.

  4. Safety and tolerability of intrathecal liposomal cytarabine as central nervous system prophylaxis in patients with acute lymphoblastic leukemia.

    PubMed

    Valentin, Angelika; Troppan, Katharina; Pfeilstöcker, Michael; Nösslinger, Thomas; Linkesch, Werner; Neumeister, Peter

    2014-08-01

    Central nervous system recurrence in acute lymphoblastic leukemia (ALL) occurs in up to 15% of patients and is frequently associated with poor outcome. The purpose of our study was to evaluate the efficacy and safety of a slow-release liposomal formulation of cytarabine for intrathecal (IT) meningeal prophylaxis in patients suffering from ALL. Forty patients aged 20-77 years (median 36) were preventively treated with a total of 96 (range 1-6) single doses containing 50 mg of liposomal cytarabine on a compassionate use basis. After a median observation period of 23 months (range 2-118) only two patients experienced a combined medullary-leptomeningeal disease recurrence after primary diagnosis. Except for headache grade 2 in two patients, no specific toxicity attributable to IT liposomal cytarabine application was noted. Long-term neurological side effects were not observed. IT liposomal cytarabine therapy with concomitant dexamethasone appears to be feasible and well tolerated.

  5. Obesity as the initial manifestation of central nervous system relapse of acute lymphoblastic leukemia: case report and literature review.

    PubMed

    Zhang, Li-Dan; Li, Yan-Hong; Ke, Zhi-Yong; Huang, Li-Bin; Luo, Xue-Qun

    2012-01-01

    A 6-year-old boy with acute lymphoblastic leukemia in remission experienced hyperphagia, obesity, and emotional disorders. Cytomorphologic examination of cerebral spinal fluid (CSF) and cranial MRI did not help in differentiating between central nervous system leukemia (CNSL) and other CNS diseases including tuberculosis in this boy. Flow cytometric CSF analysis on repeated lumber puncture detected lymphoblasts, while microscopic CSF examination did not definitively show relapse disease. The diagnosis of CNSL was thus made and confirmed by the response to leukemia treatment. Obesity can be the first manifestation of CNSL and the diagnosis can be challenging. A combination of CSF cytomorphology, CSF flow cytometry, and cranial MRI can be useful in the diagnosis of the disease. Two mechanisms of CNSL-related obesity are discussed based on the literature review.

  6. Reduced defense of central blood volume during acute lower body negative pressure-induced hypovolemic circulatory stress in aging women.

    PubMed

    Lindenberger, Marcus; Länne, Toste

    2012-06-01

    Elderly humans are more vulnerable to trauma and hemorrhage than young and elderly men and respond with decreased defense of central blood volume during acute experimental hypovolemia induced by lower body negative pressure (LBNP). However, these defense mechanisms have not been evaluated in elderly women. The aim of this study was to determine the effectiveness of compensatory responses to defend central blood volume during experimental hypovolemia in elderly and young women. Cardiovascular responses in 34 women, 12 elderly (66 ± 1 years) and 22 young women (23 ± 0.4 years), were studied during experimental hypovolemia induced by LBNP of 11 to 44 mmHg. Air plethysmography was used to assess the capacitance response (redistribution of peripheral venous blood to the central circulation) as well as net capillary fluid transfer from tissue to blood in the arm. Lower body negative pressure seemed to create comparable hypovolemia measured as total calf volume increase in elderly and young women. Heart rate increased less in elderly women (LBNP of 44 mmHg: 20 ± 2 vs. 37 ± 4%; P < 0.01) but with similar (%) increase in forearm vascular resistance. Mobilization of capacitance blood from the peripheral circulation was both slower and decreased by ∼60% in elderly women (P < 0.001), and net capillary fluid absorption from surrounding tissues was reduced by ∼40% (P < 0.01, LBNP of 44 mmHg). Elderly women responded with less increase in heart rate but with equal forearm vascular resistance (%) response during LBNP. Furthermore, the compensatory capacitance response was both slower and substantially decreased, and net capillary fluid absorption considerably reduced, collectively indicating less efficiency to defend central blood volume in elderly than in young women.

  7. Central Sleep Apnoea Is Related to the Severity and Short-Term Prognosis of Acute Coronary Syndrome

    PubMed Central

    Sánchez-de-la-Torre, Alicia; Sánchez-de-la-Torre, Manuel; Aldomá, Albina; Worner, Fernando; Galera, Estefanía; Seminario, Asunción; Torres, Gerard; Dalmases, Mireia; Montserrat, Josep M.; Garmendia, Onintza; Barbé, Ferran

    2016-01-01

    Objective To evaluate the relation of central sleep apnoea (CSA) to the severity and short-term prognosis of patients who experience acute coronary syndrome (ACS). Methods Observational study with cross-sectional and longitudinal analyses. Patients acutely admitted to participating hospitals because of ACS underwent respiratory polygraphy during the first 24 to 72 h. CSA was defined as an apnoea-hypopnoea index (AHI) >15 events•h-1 (>50% of central apnoeas). ACS severity (Killip class, ejection fraction, number of diseased vessels and peak plasma troponin) was evaluated at baseline, and short-term prognosis (length of hospitalization, complications and mortality) was evaluated at discharge. Results A total of 68 CSA patients (AHI 31±18 events•h−1, 64±12 years, 87% males) and 92 controls (AHI 7±5 events•h−1, 62±12 years, 84% males) were included in the analyses. After adjusting for age, body mass index, hypertension and smoking status, patients diagnosed with CSA spent more days in the coronary unit compared with controls (3.7±2.9 vs. 1.5±1.7; p<0.001) and had a worse Killip class (Killip I: 16% vs. 96%; p<0.001). No differences were observed in ejection fraction estimates. Conclusions CSA patients exhibited increased ACS severity as indicated by their Killip classification. These patients had a worse prognosis, with longer lengths of stay in the coronary care units. Our results highlight the relevance of CSA in patients suffering ACS episodes and suggest that diagnosing CSA may be a useful strategy to improve the management of certain ACS patients. PMID:27880845

  8. Impact of Initial Central Venous Pressure on Outcomes of Conservative versus Liberal Fluid Management in Acute Respiratory Distress Syndrome

    PubMed Central

    Semler, Matthew W.; Wheeler, Arthur P.; Thompson, B. Taylor; Bernard, Gordon R.; Wiedemann, Herbert P.; Rice, Todd W.

    2016-01-01

    Objective In acute respiratory distress syndrome (ARDS), conservative fluid management increases ventilator-free days without affecting mortality. Response to fluid management may differ based on patients’ initial central venous pressure (CVP). We hypothesized initial CVP would modify the effect of fluid management on outcomes. Design Retrospective analysis of the Fluid and Catheter Treatment Trial, a multicenter randomized trial comparing conservative to liberal fluid management in ARDS. We examined the relationship between initial CVP, fluid strategy, and 60-day mortality in univariate and multivariable analysis. Setting Twenty acute care hospitals. Patients Nine hundred and thirty-four ventilated ARDS patients with a CVP available at enrollment, 609 without baseline shock (for whom fluid balance was managed by study protocol). Interventions None. Measurements and Main Results Among patients without baseline shock, those with initial CVP > 8 mmHg experienced similar mortality with conservative and liberal fluid management (18% versus 18%, p=0.928), whereas those with CVP ≤8 mmHg experienced lower mortality with a conservative strategy (17% versus 36%, p=0.005). Multivariable analysis demonstrated an interaction between initial CVP and the effect of fluid strategy on mortality (p=0.031). At higher initial CVPs, the difference in treatment between arms was predominantly furosemide administration, which was not associated with mortality (p=0.122). At lower initial CVPs, the difference between arms was predominantly fluid administration, with additional fluid associated with increased mortality (p=0.013). Conclusions Conservative fluid management decreases mortality for ARDS patients with a low initial central venous pressure. In this population, the administration of intravenous fluids appears to increase mortality. PMID:26741580

  9. Pharmacotherapies for Retinal Detachment.

    PubMed

    Wubben, Thomas J; Besirli, Cagri G; Zacks, David N

    2016-07-01

    Retinal detachment is an important cause of visual loss. Currently, surgical techniques, including vitrectomy, scleral buckle, and pneumatic retinopexy, are the only means to repair retinal detachment and restore vision. However, surgical failure rates may be as high as 20%, and visual outcomes continue to vary secondary to multiple processes, including postoperative cystoid macular edema, epiretinal membrane formation, macular folds, and, ultimately, photoreceptor death. Therefore, pharmacotherapies are being sought to aid the success rates of modern surgical techniques and reduce or slow the degeneration of photoreceptors during retinal detachment. This review discusses potential therapeutic avenues that aid in retinal reattachment, reduce the rate of retinal redetachment by limiting proliferative vitreoretinopathy, and protect against photoreceptor cell death.

  10. Central nervous system involvement at first relapse in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy without intrathecal prophylaxis

    PubMed Central

    Montesinos, Pau; Díaz-Mediavilla, Joaquín; Debén, Guillermo; Prates, Virginia; Tormo, Mar; Rubio, Vicente; Pérez, Inmaculada; Fernández, Isolda; Viguria, Maricruz; Rayón, Chelo; González, José; de la Serna, Javier; Esteve, Jordi; Bergua, Juan M.; Rivas, Concha; González, Marcos; González, Jose D.; Negri, Silvia; Brunet, Salut; Lowenberg, Bob; Sanz, Miguel A.

    2009-01-01

    Background The prevalence of and risk factors for central nervous system recurrence in patients with acute promyelocytic leukemia are not well established and remain a controversial matter. Design and Methods Between 1996 and 2005, 739 patients with newly diagnosed acute promyelocytic leukemia enrolled in two consecutive trials (PETHEMA LPA96 and LPA99) received induction therapy with all-trans retinoic acid and idarubicin. Consolidation therapy comprised three courses of anthracycline monochemotherapy (LPA96), with all-trans retinoic acid and reinforced doses of idarubicin in patients with an intermediate or high risk of relapse (LPA99). Central nervous system prophylaxis was not given. Results Central nervous system relapse was documented in 11 patients. The 5-year cumulative incidence of central nervous system relapse was 1.7% (LPA96 3.2% and LPA99 1.2%; p=0.09). The cumulative incidence was 0%, 0.8%, and 5.5% in low-, intermediate-, and high-risk patients, respectively. Relapse risk score (p=0.0001) and the occurrence of central nervous system hemorrhage during induction (5-year cumulative incidence 18.7%, p=0.006) were independent risk factors for central nervous system relapse. Conclusions This study shows a low incidence of central nervous system relapse in patients with acute promyelocytic leukemia following therapy with all-trans retinoic acid and anthracycline without specific central nervous system prophylaxis. Central nervous system relapse was significantly associated with high white blood cell counts and prior central nervous system hemorrhage, which emerged as independent prognostic factors. PMID:19608685

  11. Integrated computer-aided retinal photocoagulation system

    NASA Astrophysics Data System (ADS)

    Barrett, Steven F.; Wright, Cameron H. G.; Oberg, Erik D.; Rockwell, Benjamin A.; Cain, Clarence P.; Jerath, Maya R.; Rylander, Henry G., III; Welch, Ashley J.

    1996-05-01

    Successful retinal tracking subsystem testing results in vivo on rhesus monkeys using an argon continuous wave laser and an ultra-short pulse laser are presented. Progress on developing an integrated robotic retinal laser surgery system is also presented. Several interesting areas of study have developed: (1) 'doughnut' shaped lesions that occur under certain combinations of laser power, spot size, and irradiation time complicating measurements of central lesion reflectance, (2) the optimal retinal field of view to achieve simultaneous tracking and lesion parameter control, and (3) a fully digital versus a hybrid analog/digital tracker using confocal reflectometry integrated system implementation. These areas are investigated in detail in this paper. The hybrid system warrants a separate presentation and appears in another paper at this conference.

  12. Central hemodynamic responses during acute high-intensity interval exercise and moderate continuous exercise in patients with heart failure.

    PubMed

    Gayda, Mathieu; Normandin, Eve; Meyer, Philippe; Juneau, Martin; Haykowsky, Mark; Nigam, Anil

    2012-12-01

    The aim of this study was to compare the acute hemodynamic responses during high-intensity intermittent exercise (HIIE) session compared with moderate-intensity continuous exercise (MICE) session in patients with heart failure and reduced ejection fraction (HFREF). Thirteen patients with HFREF (age, 59 ± 6 years; left ventricular ejection fraction, 27% ± 6%; New York Heart Association class I to III) were randomly assigned to a single session of HIIE (2 × 8 min) corresponding to 30 s at 100% of peak power output (PPO) and 30 s passive recovery intervals or to a MICE (22 min) at 60% of PPO. Gas exchange and central hemodynamic parameters (cardiac bioimpedance) were measured continuously during exercise. Oxygen uptake, stroke volume (SV), cardiac output (CO), and arterio-venous difference (C(a-v)O(2)) were compared. Mean oxygen uptake and ventilation were lower during HIIE vs. MICE. CO, SV, and C(a-v)O(2)) were not different between MICE and HIIE. Optimized HIIE was well tolerated (similar perceived exertion) and no significant ventricular arrhythmias and (or) abnormal blood pressure responses occurred during HIEE session. Compared with MICE, optimized HIIE elicited similar central hemodynamic and C(a-v)O(2) responses in HFREF patients with lower oxygen uptake and ventilation. HIIE may be an efficient exercise training modality in patients with HFREF.

  13. Acute myeloid leukemia with monosomy 7, ectopic virus integration site-1 overexpression and central diabetes insipidus: A case report.

    PubMed

    Ma, Hongbing; Yang, Jing; Xiang, Bing; Jia, Yongqian

    2015-06-01

    Central diabetes insipidus (DI) is a rare complication in patients with acute myeloid leukemia (AML), typically occurring in patients with abnormalities of chromosomes 3 or 7. The association between AML with monosomy 7 and DI has been described in a number of studies; however, DI has been rarely reported in cases of ectopic virus integration site-1 (EVI1)-positive AML with monosomy 7. The current study reports a case of AML with monosomy 7 and EVI1 overexpression, with central DI as the initial symptom. The patient was an 18-year-old female who presented with polyuria and polydipsia. Bone marrow aspiration revealed 83.5% myeloperoxidase-positive blasts without trilineage myelodysplasia. The karyotype was 45,XX,-7, and the patient presented monosomy 7 and EVI1 overexpression (-7/EVI1(+)) without 3q aberration. Treatment with induction therapy was unsuccessful. To the best of our knowledge, this is the second case of DI-AML with -7/EVI1(+) and without a 3q aberration. The possible mechanisms associated with EVI1, monosomy 7 and DI were investigated.

  14. Retinal remodeling in inherited photoreceptor degenerations.

    PubMed

    Marc, Robert E; Jones, Bryan W

    2003-10-01

    Photoreceptor degenerations initiated in rods or the retinal pigmented epithelium usually evoke secondary cone death and sensory deafferentation of the surviving neural retina. In the mature central nervous system, deafferentation evokes atrophy and connective re-patterning. It has been assumed that the neural retina does not remodel, and that it is a passive survivor. Screening of advanced stages of human and rodent retinal degenerations with computational molecular phenotyping has exposed a prolonged period of aggressive negative remodeling in which neurons migrate along aberrant glial columns and seals, restructuring the adult neural retina (1). Many neurons die, but survivors rewire the remnant inner plexiform layer (IPL), forming thousands of novel ectopic microneuromas in the remnant inner nuclear layer (INL). Bipolar and amacrine cells engage in new circuits that are most likely corruptive. Remodeling in human and rodent retinas emerges regardless of the molecular defects that initially trigger retinal degenerations. Although remodeling may constrain therapeutic intervals for molecular, cellular, or bionic rescue, the exposure of intrinsic retinal remodeling by the removal of sensory control in retinal degenerations suggests that neuronal organization in the normal retina may be more plastic than previously believed.

  15. No Evidence for Retinal Damage Evolving from Reduced Retinal Blood Flow in Carotid Artery Disease

    PubMed Central

    Heßler, Henning; Zimmermann, Hanna; Oberwahrenbrock, Timm; Kadas, Ella Maria; Mikolajczak, Janine; Brandt, Alexander U.; Kauert, Andreas; Paul, Friedemann; Schreiber, Stephan J.

    2015-01-01

    Introduction. Carotid artery disease (CAD) comprising high-grade internal carotid artery stenosis (CAS) or carotid artery occlusion (CAO) may lead to ipsilateral impaired cerebral blood flow and reduced retinal blood supply. Objective. To examine the influence of chronic CAD on retinal blood flow, retinal morphology, and visual function. Methods. Patients with unilateral CAS ≥ 50% (ECST criteria) or CAO were grouped according to the grade of the stenosis and to the flow direction of the ophthalmic artery (OA). Retinal perfusion was measured by transorbital duplex ultrasound, assessing central retinal artery (CRA) blood flow velocities. In addition, optic nerve and optic nerve sheath diameter were measured. Optical coherence tomography (OCT) was performed to study retinal morphology. Visual function was assessed using high- and low-contrast visual paradigms. Results. Twenty-seven patients were enrolled. Eyes with CAS ≥ 80%/CAO and retrograde OA blood flow showed a significant reduction in CRA peak systolic velocity (no-CAD side: 0.130 ± 0.035 m/s, CAS/CAO side: 0.098 ± 0.028; p = 0.005; n = 12). OCT, optic nerve thicknesses, and visual functional parameters did not show a significant difference. Conclusion. Despite assessable hemodynamic effects, chronic high-grade CAD does not lead to gaugeable morphological or functional changes of the retina. PMID:26558275

  16. Classification of left and right eye retinal images

    NASA Astrophysics Data System (ADS)

    Tan, Ngan Meng; Liu, Jiang; Wong, Damon W. K.; Zhang, Zhuo; Lu, Shijian; Lim, Joo Hwee; Li, Huiqi; Wong, Tien Yin

    2010-03-01

    Retinal image analysis is used by clinicians to diagnose and identify, if any, pathologies present in a patient's eye. The developments and applications of computer-aided diagnosis (CAD) systems in medical imaging have been rapidly increasing over the years. In this paper, we propose a system to classify left and right eye retinal images automatically. This paper describes our two-pronged approach to classify left and right retinal images by using the position of the central retinal vessel within the optic disc, and by the location of the macula with respect to the optic nerve head. We present a framework to automatically identify the locations of the key anatomical structures of the eye- macula, optic disc, central retinal vessels within the optic disc and the ISNT regions. A SVM model for left and right eye retinal image classification is trained based on the features from the detection and segmentation. An advantage of this is that other image processing algorithms can be focused on regions where diseases or pathologies and more likely to occur, thereby increasing the efficiency and accuracy of the retinal CAD system/pathology detection. We have tested our system on 102 retinal images, consisting of 51 left and right images each and achieved and accuracy of 94.1176%. The high experimental accuracy and robustness of this system demonstrates that there is potential for this system to be integrated and applied with other retinal CAD system, such as ARGALI, for a priori information in automatic mass screening and diagnosis of retinal diseases.

  17. Retinal vascular regeneration.

    PubMed

    Otani, Atsushi; Friedlander, Martin

    2005-01-01

    We discuss the potential use of stem cells for therapeutic angiogenesis in the treatment of retinal diseases. We demonstrate that the clinical utility of these EPC may be not limited in the treatment of ischemic retinal diseases but may also have application for the treatment of retinal degenerative disorders and for a form of cell-based gene therapy. One of the greatest potential benefits of bone marrow derived EPC therapy is the possible use of autologous grafts. Nonetheless, potential toxicities and unregulated cell growth will need to be carefully evaluated before this approach is brought to the clinics.

  18. New perspectives on central and peripheral immune responses to acute traumatic brain injury

    PubMed Central

    2012-01-01

    Traumatic injury to the brain (TBI) results in a complex set of responses involving various symptoms and long-term consequences. TBI of any form can cause cognitive, behavioral and immunologic changes in later life, which underscores the problem of underdiagnosis of mild TBI that can cause long-term neurological deficits. TBI disrupts the blood–brain barrier (BBB) leading to infiltration of immune cells into the brain and subsequent inflammation and neurodegeneration. TBI-induced peripheral immune responses can also result in multiorgan damage. Despite worldwide research efforts, the methods of diagnosis, monitoring and treatment for TBI are still relatively ineffective. In this review, we delve into the mechanism of how TBI-induced central and peripheral immune responses affect the disease outcome and discuss recent developments in the continuing effort to combat the consequences of TBI and new ways to enhance repair of the damaged brain. PMID:23061919

  19. Inner retinal change in a novel rd1-FTL mouse model of retinal degeneration

    PubMed Central

    Greferath, Ursula; Anderson, Emily E.; Jobling, Andrew I.; Vessey, Kirstan A.; Martinez, Gemma; de Iongh, Robb U.; Kalloniatis, Michael; Fletcher, Erica L.

    2015-01-01

    While photoreceptor loss is the most devastating result of inherited retinal degenerations such as retinitis pigmentosa, inner retinal neurons also undergo significant alteration. Detailing these changes has become important as many vision restorative therapies target the remaining neurons. In this study, the rd1-Fos-Tau-LacZ (rd1-FTL) mouse model was used to explore inner retinal change at a late stage of retinal degeneration, after the loss of photoreceptor nuclei. The rd1-FTL model carries a mutation in the phosphodiesterase gene, Pde6b, and an axonally targeted transgenic beta galactosidase reporter system under the control of the c-fos promoter. Retinae of transgenic rd1-FTL mice and control FTL animals aged 2–12 months were processed for indirect fluorescence immunocytochemistry. At 2 months of age, a time when the majority of photoreceptor nuclei are lost, there was negligible c-fos reporter (FTL) expression, however, from 4 months, reporter expression was observed to increase within subpopulations of amacrine and ganglion cells within the central retina. These areas of inner retinal FTL expression coincided with regions that contained aberrant Müller cells. Specifically, these cells exhibited reduced glutamine synthetase and Kir4.1 immunolabelling, whilst showing evidence of proliferative gliosis (increased cyclinD1 and glial fibrillary acidic protein expression). These changes were limited to distinct regions where cone photoreceptor terminals were absent. Overall, these results highlight that distinct areas of the rd1-FTL central retina undergo significant glial alterations after cone photoreceptor loss. These areas coincide with up-regulation of the c-fos reporter in the inner retina, which may represent a change in neuronal function/plasticity. The rd1-FTL mouse is a useful model system to probe changes that occur in the inner retina at later stages of retinal degeneration. PMID:26283925

  20. Retinal oximeter for the blue-green oximetry technique

    NASA Astrophysics Data System (ADS)

    Denninghoff, Kurt R.; Sieluzycka, Katarzyna B.; Hendryx, Jennifer K.; Ririe, Tyson J.; Deluca, Lawrence; Chipman, Russell A.

    2011-10-01

    Retinal oximetry offers potential for noninvasive assessment of central venous oxyhemoglobin saturation (SO2) via the retinal vessels but requires a calibrated accuracy of +/-3% saturation in order to be clinically useful. Prior oximeter designs have been hampered by poor saturation calibration accuracy. We demonstrate that the blue-green oximetry (BGO) technique can provide accuracy within +/-3% in swine when multiply scattered light from blood within a retinal vessel is isolated. A noninvasive on-axis scanning retinal oximeter (ROx-3) is constructed that generates a multiwavelength image in the range required for BGO. A field stop in the detection pathway is used in conjunction with an anticonfocal bisecting wire to remove specular vessel reflections and isolate multiply backscattered light from the blood column within a retinal vessel. This design is tested on an enucleated swine eye vessel and a retinal vein in a human volunteer with retinal SO2 measurements of ~1 and ~65%, respectively. These saturations, calculated using the calibration line from earlier work, are internally consistent with a standard error of the mean of +/-2% SO2. The absolute measures are well within the expected saturation range for the site (-1 and 63%). This is the first demonstration of noninvasive on-axis BGO retinal oximetry.

  1. Retinal oximeter for the blue-green oximetry technique.

    PubMed

    Denninghoff, Kurt R; Sieluzycka, Katarzyna B; Hendryx, Jennifer K; Ririe, Tyson J; Deluca, Lawrence; Chipman, Russell A

    2011-10-01

    Retinal oximetry offers potential for noninvasive assessment of central venous oxyhemoglobin saturation (SO(2)) via the retinal vessels but requires a calibrated accuracy of ±3% saturation in order to be clinically useful. Prior oximeter designs have been hampered by poor saturation calibration accuracy. We demonstrate that the blue-green oximetry (BGO) technique can provide accuracy within ±3% in swine when multiply scattered light from blood within a retinal vessel is isolated. A noninvasive on-axis scanning retinal oximeter (ROx-3) is constructed that generates a multiwavelength image in the range required for BGO. A field stop in the detection pathway is used in conjunction with an anticonfocal bisecting wire to remove specular vessel reflections and isolate multiply backscattered light from the blood column within a retinal vessel. This design is tested on an enucleated swine eye vessel and a retinal vein in a human volunteer with retinal SO(2) measurements of ∼1 and ∼65%, respectively. These saturations, calculated using the calibration line from earlier work, are internally consistent with a standard error of the mean of ±2% SO(2). The absolute measures are well within the expected saturation range for the site (-1 and 63%). This is the first demonstration of noninvasive on-axis BGO retinal oximetry.

  2. Central review of cytogenetics is necessary for cooperative group correlative and clinical studies of adult acute leukemia: The Cancer and Leukemia Group B experience

    PubMed Central

    Mrózek, Krzysztof; Carroll, Andrew J.; Maharry, Kati; Rao, Kathleen W.; Patil, Shivanand R.; Pettenati, Mark J.; Watson, Michael S.; Arthur, Diane C.; Tantravahi, Ramana; Heerema, Nyla A.; Koduru, Prasad R. K.; Block, AnneMarie W.; Qumsiyeh, Mazin B.; Edwards, Colin G.; Sterling, Lisa J.; Holland, Kelsi B.; Bloomfield, Clara D.

    2009-01-01

    The Cancer and Leukemia Group B has performed central review of karyotypes submitted by institutional cytogenetics laboratories from patients with acute myeloid (AML) and acute lymphoblastic (ALL) leukemia since 1986. We assessed the role of central karyotype review in maintaining accurate, high quality cytogenetic data for clinical and translational studies using two criteria: the proportion of karyotypes rejected (i.e. inadequate), and, among accepted (i.e. adequate) cases, the proportion of karyotypes whose interpretation was changed on central karyotype review. We compared the first four years during which central karyotype review was performed with a recent four-year period and found that the proportion of rejected samples decreased significantly for both AML and ALL. However, during the latter period, central karyotype reviews still found 8% of AML and 16% of ALL karyotypes inadequate. Among adequate cases, the karyotype was revised in 26% of both AML and ALL samples. Some revisions resulted in changing the patients’ assignment to particular World Health Organization diagnostic categories and/or moving patients from one prognostic group to another. Overall, when both data on rejection rates and data on karyotype revisions made in accepted cases were considered together, 32% of AML and 38% of ALL samples submitted were either rejected or revised on central karyotype review during the recent 4-year period. These data underscore the necessity of continued central karyotype review in multi-institutional cooperative group studies. PMID:18636143

  3. Connexin43 mimetic peptide reduces vascular leak and retinal ganglion cell death following retinal ischaemia.

    PubMed

    Danesh-Meyer, Helen V; Kerr, Nathan M; Zhang, Jie; Eady, Elizabeth K; O'Carroll, Simon J; Nicholson, Louise F B; Johnson, Cameron S; Green, Colin R

    2012-02-01

    Connexin43 gap junction protein is expressed in astrocytes and the vascular endothelium in the central nervous system. It is upregulated following central nervous system injury and is recognized as playing an important role in modulating the extent of damage. Studies that have transiently blocked connexin43 in spinal cord injury and central nervous system epileptic models have reported neuronal rescue. The purpose of this study was to investigate neuronal rescue following retinal ischaemia-reperfusion by transiently blocking connexin43 activity using a connexin43 mimetic peptide. A further aim was to evaluate the effect of transiently blocking connexin43 on vascular permeability as this is known to increase following central nervous system ischaemia. Adult male Wistar rats were exposed to 60 min of retinal ischaemia. Treatment groups consisted of no treatment, connexin43 mimetic peptide and scrambled peptide. Retinas were then evaluated at 1-2, 4, 8 and 24 h, and 7 and 21 days post-ischaemia. Evans blue dye leak from retinal blood vessels was used to assess vascular leakage. Blood vessel integrity was examined using isolectin-B4 labelling. Connexin43 levels and astrocyte activation (glial fibrillary acidic protein) were assessed using immunohistochemistry and western blot analysis. Retinal whole mounts and retinal ganglion cell counts were used to quantify neurodegeneration. An in vitro cell culture model of endothelial cell ischaemia was used to assess the effect of connexin43 mimetic peptide on endothelial cell survival and connexin43 hemichannel opening using propidium iodide dye uptake. We found that retinal ischaemia-reperfusion induced significant vascular leakage and disruption at 1-2, 4 and 24 h following injury with a peak at 4 h. Connexin43 immunoreactivity was significantly increased at 1-2, 4, 8 and 24 h post ischaemia-reperfusion injury co-localizing with activated astrocytes, Muller cells and vascular endothelial cells. Connexin43 mimetic peptide

  4. Sodium nitrite induces acute central nervous system toxicity in guinea pigs exposed to systemic cell-free hemoglobin

    SciTech Connect

    Buehler, Paul W.; Butt, Omer I.; D'Agnillo, Felice

    2011-06-10

    Highlights: {yields} Toxicological implications associated with the use of NaNO{sub 2} therapy to treat systemic cell-free Hb exposure are not well-defined. {yields} Systemic Hb exposure followed by NaNO{sub 2} infusion induces acute CNS toxicities in guinea pigs. {yields} These CNS effects were not reproduced by the infusion of cell-free Hb or NaNO{sub 2} alone. {yields} NaNO{sub 2}-mediated oxidation of cell-free Hb may play a causative role in the observed CNS changes. -- Abstract: Systemic cell-free hemoglobin (Hb) released via hemolysis disrupts vascular homeostasis, in part, through the scavenging of nitric oxide (NO). Sodium nitrite (NaNO{sub 2}) therapy can attenuate the hypertensive effects of Hb. However, the chemical reactivity of NaNO{sub 2} with Hb may enhance heme- or iron-mediated toxicities. Here, we investigate the effect of NaNO{sub 2} on the central nervous system (CNS) in guinea pigs exposed to systemic cell-free Hb. Intravascular infusion of NaNO{sub 2}, at doses sufficient to alleviate Hb-mediated blood pressure changes, reduced the expression of occludin, but not zona occludens-1 (ZO-1) or claudin-5, in cerebral tight junctions 4 h after Hb infusion. This was accompanied by increased perivascular heme oxygenase-1 expression, neuronal iron deposition, increased astrocyte and microglial activation, and reduced expression of neuron-specific nuclear protein (NeuN). These CNS changes were not observed in animals treated with Hb or NaNO{sub 2} alone. Taken together, these findings suggest that the use of nitrite salts to treat systemic Hb exposure may promote acute CNS toxicity.

  5. Bone marrow–derived stem cells preserve cone vision in retinitis pigmentosa

    PubMed Central

    Smith, Lois E.H.

    2004-01-01

    Retinitis pigmentosa is a heritable group of blinding diseases resulting from loss of photoreceptors, primarily rods and secondarily cones, that mediate central vision. Loss of retinal vasculature is a presumed metabolic consequence of photoreceptor degeneration. A new study shows that autologous bone marrow–derived lineage-negative hematopoietic stem cells, which incorporate into the degenerating blood vessels in two murine models of retinitis pigmentosa, rd1 and rd10, prevent cone loss. The use of autologous bone marrow might avoid problems with rejection while preserving central cone vision in a wide variety of genetically disparate retinal degenerative diseases. PMID:15372096

  6. Acute Cerebrovascular Radiation Syndrome: Radiation Neurotoxicity , mechanisms of CNS radiation injury, advanced countermeasures for Radiation Protection of Central Nervous System.

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri; Jones, Jeffrey; Maliev, Slava

    Key words: Cerebrovascular Acute Radiation Syndrome (Cv ARS), Radiation Neurotoxins (RNT), Neurotransmitters, Radiation Countermeasures, Antiradiation Vaccine (ArV), Antiradiation Blocking Antibodies, Antiradiation Antidote. Psychoneuroimmunology, Neurotoxicity. ABSTRACT: To review the role of Radiation Neurotoxins in triggering, developing of radiation induced central nervous system injury. Radiation Neurotoxins - rapidly acting blood toxic lethal agent, which activated after irradiation and concentrated, circulated in interstitial fluid, lymph, blood with interactions with cell membranes, receptors and cell compartments. Radiation Neurotoxins - biological molecules with high enzymatic activity and/or specific lipids and activated or modified after irradiation. The Radiation Neurotoxins induce increased permeability of blood vessels, disruption of the blood-brain barrier, blood-cerebrospinal fluid (CSF) barrier and developing severe disorder of blood macro- and micro-circulation. Principles of Radiation Psychoneuro-immunology and Psychoneuro-allergology were applied for determination of pathological processes developed after irradiation or selective administration of Radiation Neurotoxins to radiation naïve mammals. Effects of radiation and exposure to radiation can develop severe irreversible abnormalities of Central Nervous System, brain structures and functions. Antiradiation Vaccine - most effective, advanced methods of protection, prevention, mitigation and treatment and was used for of Acute Radiation Syndromes and elaboration of new technology for immune-prophylaxis and immune-protection against ϒ, Heavy Ion, Neutron irradiation. Results of experiments suggested that blocking, antitoxic, antiradiation antibodies can significantly reduce toxicity of Radiation Toxins. New advanced technology include active immune-prophylaxis with Antiradiation Vaccine and Antiradiation therapy that included specific blocking antibodies to Radiation Neurotoxins

  7. Retinal detachment in pseudophakia.

    PubMed

    Galin, M A; Poole, T A; Obstbaum, S A

    1979-07-01

    In a series of cataract patients excluding myopic individuals, under age 60 years, and cases in which vitreous loss occurred, retinal detachment was no less frequent after intracapsular cataract extraction and Sputnik iris supported lenses than in controls. Both groups were followed up for a minimum of two years. The detachments predominantly occurred from retinal breaks in areas of the retina that looked normal preoperatively.

  8. Retinal dysplasia of holoprosencephaly.

    PubMed

    Gorovoy, Ian R; Layer, Noelle; de Alba Campomanes, Alejandra G

    2014-03-04

    Retinal dysplasia occurs in the setting of sporadic and syndromic holoprosencephaly, which often has associated ocular malformations. The pathology of this dysplasia, which includes rosettes, has been previously described. However, its funduscopic findings have not been well documented. The authors present the fundus images of a patient with severe holoprosencephaly with retinal dysplasia and bilateral optic nerve colobomas that resulted in death 2 weeks after birth.

  9. Hepatitis E virus infection in patients with acute non-A, non-B, non-C hepatitis in Central Brazil

    PubMed Central

    de Freitas, Nara Rubia; de Santana, Edna Braz Rocha; Silva, Ágabo Macedo da Costa e; da Silva, Sueli Meira; Teles, Sheila Araújo; Gardinali, Noemi Rovaris; Pinto, Marcelo Alves; Martins, Regina Maria Bringel

    2016-01-01

    Hepatitis E virus (HEV) infection has a worldwide distribution and represents an important cause of acute hepatitis. This study aims to investigate the occurrence of HEV infection and factors associated with this infection in patients with acute non-A, non-B, non-C hepatitis in Central Brazil. From April 2012 to October 2014, a cross-sectional study was conducted among 379 patients with acute non-A, non-B, non-C hepatitis in the City of Goiania, Central Brazil. Serum samples of all patients were tested for serological markers of HEV infection (anti-HEV IgM and IgG) by ELISA. Positive samples were confirmed using immunoblot test. Anti-HEV IgM and IgG positive samples were tested for HEV RNA. Of the 379 serum samples, one (0.3%) and 20 (5.3%) were positive for anti-HEV IgM and IgG, respectively. HEV RNA was not found in any sample positive for IgM and/or IgG anti-HEV. After multivariate analysis, low education level was independently associated with HEV seropositivity (p = 0.005), as well as living in rural area, with a borderline p-value (p = 0.056). In conclusion, HEV may be responsible for sporadic self-limited cases of acute hepatitis in Central Brazil. PMID:27759769

  10. Self-organising aggregates of zebrafish retinal cells for investigating mechanisms of neural lamination.

    PubMed

    Eldred, Megan K; Charlton-Perkins, Mark; Muresan, Leila; Harris, William A

    2017-03-15

    To investigate the cell-cell interactions necessary for the formation of retinal layers, we cultured dissociated zebrafish retinal progenitors in agarose microwells. Within these wells, the cells re-aggregated within hours, forming tight retinal organoids. Using a Spectrum of Fates zebrafish line, in which all different types of retinal neurons show distinct fluorescent spectra, we found that by 48 h in culture, the retinal organoids acquire a distinct spatial organisation, i.e. they became coarsely but clearly laminated. Retinal pigment epithelium cells were in the centre, photoreceptors and bipolar cells were next most central and amacrine cells and retinal ganglion cells were on the outside. Image analysis allowed us to derive quantitative measures of lamination, which we then used to find that Müller glia, but not RPE cells, are essential for this process.

  11. Self-organising aggregates of zebrafish retinal cells for investigating mechanisms of neural lamination

    PubMed Central

    Eldred, Megan K.; Charlton-Perkins, Mark; Muresan, Leila

    2017-01-01

    ABSTRACT To investigate the cell-cell interactions necessary for the formation of retinal layers, we cultured dissociated zebrafish retinal progenitors in agarose microwells. Within these wells, the cells re-aggregated within hours, forming tight retinal organoids. Using a Spectrum of Fates zebrafish line, in which all different types of retinal neurons show distinct fluorescent spectra, we found that by 48 h in culture, the retinal organoids acquire a distinct spatial organisation, i.e. they became coarsely but clearly laminated. Retinal pigment epithelium cells were in the centre, photoreceptors and bipolar cells were next most central and amacrine cells and retinal ganglion cells were on the outside. Image analysis allowed us to derive quantitative measures of lamination, which we then used to find that Müller glia, but not RPE cells, are essential for this process. PMID:28174240

  12. A novel method for detection of preferred retinal locus (PRL) through simple retinal image processing using MATLAB

    NASA Astrophysics Data System (ADS)

    Kalikivayi, V.; Pal, Sudip; Ganesan, A. R.

    2013-09-01

    simple and new technique for detection of `Preferred Retinal Locus' (PRL) in human eye is proposed in this paper. Simple MATLAB algorithms for estimating RGB pixel intensity values of retinal images were used. The technique proved non-existence of `S' cones in Fovea Centralis and also proposes that rods are involved in blue color perception. Retinal images of central vision loss and normal retina were taken for image processing. Blue minimum, Red maximum and Red+Green maximum were the three methods used in detecting PRL. Comparative analyses were also performed for these methods with patient's age and visual acuity.

  13. Structural and Functional Changes of the Human Macula during Acute Exposure to High Altitude

    PubMed Central

    Fischer, M. Dominik; Willmann, Gabriel; Schatz, Andreas; Schommer, Kai; Zhour, Ahmad; Zrenner, Eberhart; Bartz-Schmidt, Karl U.; Gekeler, Florian

    2012-01-01

    Background This study aimed to quantify structural and functional changes at the macula during acute exposure to high altitude and to assess their structure/function relationship. This work is related to the Tuebingen High Altitude Ophthalmology (THAO) study. Methodology/Principal Findings Spectral domain optical coherence tomography and microperimetry were used to quantify changes of central retinal structure and function in 14 healthy subjects during acute exposure to high altitude (4559 m). High-resolution volume scans and fundus-controlled microperimetry of the posterior pole were performed in addition to best-corrected visual acuity (BCVA) measurements and assessment of acute mountain sickness. Analysis of measurements at altitude vs. baseline revealed increased total retinal thickness (TRT) in all four outer ETDRS grid subfields during acute altitude exposure (TRTouter = 2.80±1.00 μm; mean change±95%CI). This change was inverted towards the inner four subfields (TRTinner = −1.89±0.97 μm) with significant reduction of TRT in the fovea (TRTfoveal = −6.62±0.90 μm) at altitude. BCVA revealed no significant difference compared to baseline (0.06±0.08 logMAR). Microperimetry showed stable mean sensitivity in all but the foveal subfield (MSfoveal = −1.12±0.68 dB). At baseline recordings before and >2 weeks after high altitude exposure, all subjects showed equal levels with no sign of persisting structural or functional sequels. Conclusions/Significance During acute exposure to high altitude central retinal thickness is subject to minor, yet statistically significant changes. These alterations describe a function of eccentricity with an increase in regions with relatively higher retinal nerve fiber content and vascular arcades. However, these changes did not correlate with measures of central retinal function or acute mountain sickness. For the first time a quantitative approach has been used to assess these changes during acute, non

  14. Incidence and Clinical Outcome of Patients with Hypertensive Acute Ischemic Stroke: An Update from Tertiary Care Center of Central India

    PubMed Central

    Nayak, Amit R.; Shekhawat, Seema D.; Lande, Neha H.; Kawle, Anuja P.; Kabra, Dinesh P.; Chandak, Nitin H.; Badar, Shweta R.; Raje, Dhananjay V.; Daginawala, Hatim F.; Singh, Lokendra R.; Kashyap, Rajpal S.

    2016-01-01

    Introduction: We evaluated the incidence and clinical outcome of patients with hypertensive acute ischemic stroke (AIS) admitted to a tertiary care center in Central India. In addition, we examined the status of stroke biomarkers namely neuron-specific enolase (NSE), glial specific protein (S-100ββ), and inter-α-trypsin inhibitor heavy chain 4(ITIH4) in the serum of patients suffering from AIS with hypertension (HTN) and without HTN. Methods: A total of 104 patients with AIS were enrolled for the study. Clinical outcome and stroke biomarker levels were evaluated in them at the time of hospital discharge and then followed at 12 months and 18 months after hospital discharge. Results: HTN is a major risk factor associated with 67%(70.104) of patients with AIS. Multivariate analysis suggests higher odds of 4.088(95%Cl, 0.721–23.179) and 2.437(95%Cl, 0.721–23.179) for 12 and 18 months outcome in patients with AIS and HTN, respectively. Serum NSE and S-100ββ decreased at the time of discharge as compared to admission level in improved patients suffering from AIS with or without HTN, whereas levels of ITIH4 peptides 2 and 7 increased at the time of discharge (compared to its admission level) only in improved patients with AIS regardless of HTN or non-HTN condition. Conclusion: HTN is one of the major risk factors associated with higher risk of AIS as well as long-term unfavourable outcome after AIS in Central India region. NSE, S-100ββ, and ITIH4 were found to be independent predictors of outcome in patients with AIS irrespective of HTN and non-HTN condition. PMID:27872696

  15. Iatrogenic acute cardiac tamponade during percutaneous removal of a fractured peripherally inserted central catheter in a premature neonate.

    PubMed

    Minghui, Zou; Hujun, Cui; Li, Ma; Weidan, Chen; Yanqin, Cui; Xinxin, Chen

    2015-01-01

    Acute cardiac tamponade (ACT) is a life-threatening complication associated with a peripherally inserted central catheter (PICC) in premature neonates. We present a case of ACT in a 4-day-old male infant. On the second admission day, a PICC was inserted. After 2.5 months, chest radiography showed PICC fracture, and its distal portion had migrated into the right pulmonary artery. Percutaneous removal through cardiac catheterization was attempted. However, right ventriculography demonstrated intrapericardial spillage of contrast agents, and iatrogenic ACT was confirmed. Cardiopulmonary resuscitation (CPR) was immediately started with open-chest cardiac massage. Further surgical exploration revealed right atrial appendage perforation. After 25-min CPR, the patient restored spontaneous circulation, and removal of the foreign bodies was performed. The post-operative course was uneventful. PICC fracture is an uncommon complication, but may be life-threatening. Precaution should be taken to avoid ACT during removal of a broken PICC. Once the tamponade is diagnosed, immediate interventions are mandatory.

  16. Sodium nitrite induces acute central nervous system toxicity in guinea pigs exposed to systemic cell-free hemoglobin.

    PubMed

    Buehler, Paul W; Butt, Omer I; D'Agnillo, Felice

    2011-06-10

    Systemic cell-free hemoglobin (Hb) released via hemolysis disrupts vascular homeostasis, in part, through the scavenging of nitric oxide (NO). Sodium nitrite (NaNO(2)) therapy can attenuate the hypertensive effects of Hb. However, the chemical reactivity of NaNO(2) with Hb may enhance heme- or iron-mediated toxicities. Here, we investigate the effect of NaNO(2) on the central nervous system (CNS) in guinea pigs exposed to systemic cell-free Hb. Intravascular infusion of NaNO(2), at doses sufficient to alleviate Hb-mediated blood pressure changes, reduced the expression of occludin, but not zona occludens-1 (ZO-1) or claudin-5, in cerebral tight junctions 4h after Hb infusion. This was accompanied by increased perivascular heme oxygenase-1 expression, neuronal iron deposition, increased astrocyte and microglial activation, and reduced expression of neuron-specific nuclear protein (NeuN). These CNS changes were not observed in animals treated with Hb or NaNO(2) alone. Taken together, these findings suggest that the use of nitrite salts to treat systemic Hb exposure may promote acute CNS toxicity.

  17. Central estrogenic pathways protect against the depressant action of acute nicotine on reflex tachycardia in female rats

    SciTech Connect

    El-Mas, Mahmoud M. Fouda, Mohamed A.; El-gowilly, Sahar M.; Saad, Evan I.

    2012-02-01

    We have previously shown that acute exposure of male rats to nicotine preferentially attenuates baroreceptor-mediated control of reflex tachycardia in contrast to no effect on reflex bradycardia. Here, we investigated whether female rats are as sensitive as their male counterparts to the baroreflex depressant effect of nicotine and whether this interaction is modulated by estrogen. Baroreflex curves relating reflex chronotropic responses evoked by i.v. doses (1–16 μg/kg) of phenylephrine (PE) or sodium nitroprusside (SNP), were constructed in conscious freely moving proestrus, ovariectomized (OVX), and estrogen (50 μg/kg/day s.c., 5 days)-replaced OVX (OVXE{sub 2}) rats. Slopes of the curves were taken as a measure of baroreflex sensitivity (BRS{sub PE} and BRS{sub SNP}). Nicotine (100 μg/kg i.v.) reduced BRS{sub SNP} in OVX rats but not in proestrus or OVXE{sub 2} rats. The attenuation of reflex tachycardia by nicotine was also evident in diestrus rats, which exhibited plasma estrogen levels similar to those of OVX rats. BRS{sub PE} was not affected by nicotine in all rat preparations. Experiments were then extended to determine whether central estrogenic receptors modulate the nicotine–BRS{sub SNP} interaction. Intracisteral (i.c.) treatment of OVX rats with estrogen sulfate (0.2 μg/rat) abolished the BRS{sub SNP} attenuating effect of i.v. nicotine. This protective effect of estrogen disappeared when OVX rats were pretreated with i.c. ICI 182,780 (50 μg/rat, selective estrogen receptor antagonist). Together, these findings suggest that central neural pools of estrogen receptors underlie the protection offered by E{sub 2} against nicotine-induced baroreceptor dysfunction in female rats. -- Highlights: ► Estrogen protects against the depressant effect of nicotine on reflex tachycardia. ► The baroreflex response and estrogen status affect the nicotine–BRS interaction. ► The protection offered by estrogen is mediated via central estrogen receptors.

  18. Progressive outer retinal necrosis-like retinitis in immunocompetent hosts.

    PubMed

    Chawla, Rohan; Tripathy, Koushik; Gogia, Varun; Venkatesh, Pradeep

    2016-08-10

    We describe two young immunocompetent women presenting with bilateral retinitis with outer retinal necrosis involving posterior pole with centrifugal spread and multifocal lesions simulating progressive outer retinal necrosis (PORN) like retinitis. Serology was negative for HIV and CD4 counts were normal; however, both women were on oral steroids at presentation for suspected autoimmune chorioretinitis. The retinitis in both eyes responded well to oral valaciclovir therapy. However, the eye with the more fulminant involvement developed retinal detachment with a loss of vision. Retinal atrophy was seen in the less involved eye with preservation of vision. Through these cases, we aim to describe a unique evolution of PORN-like retinitis in immunocompetent women, which was probably aggravated by a short-term immunosuppression secondary to oral steroids.

  19. Photovoltaic retinal prosthesis

    NASA Astrophysics Data System (ADS)

    Loudin, James; Mathieson, Keith; Kamins, Ted; Wang, Lele; Galambos, Ludwig; Huie, Philip; Sher, Alexander; Harris, James; Palanker, Daniel

    2011-03-01

    Electronic retinal prostheses seek to restore sight to patients suffering from retinal degenerative disorders. Implanted electrode arrays apply patterned electrical stimulation to surviving retinal neurons, producing visual sensations. All current designs employ inductively coupled coils to transmit power and/or data to the implant. We present here the design and initial testing of a photovoltaic retinal prosthesis fabricated with a pixel density of up to 177 pixels/mm2. Photodiodes within each pixel of the subretinal array directly convert light to stimulation current, avoiding the use of bulky coil implants, decoding electronics, and wiring, and thereby reducing surgical complexity. A goggles-mounted camera captures the visual scene and transmits the data stream to a pocket processor. The resulting images are projected into the eyes by video goggles using pulsed, near infrared (~900 nm) light. Prostheses with three pixel densities (15, 55, and 177 pix/mm2) are being fabricated, and tests indicate a charge injection limit of 1.62 mC/cm2 at 25Hz. In vitro tests of the photovoltaic retinal stimulation using a 512-element microelectrode array have recorded stimulated spikes from the ganglion cells, with latencies in the 1-100ms range, and with peak irradiance stimulation thresholds varying from 0.1 to 1 mW/mm2. With 1ms pulses at 25Hz the average irradiance is more than 100 times below the IR retinal safety limit. Elicited retinal response disappeared upon the addition of synaptic blockers, indicating that the inner retina is stimulated rather than the ganglion cells directly, and raising hopes that the prosthesis will preserve some of the retina's natural signal processing.

  20. Improving the therapeutic window of retinal photocoagulation by spatial and temporal modulation of the laser beam

    NASA Astrophysics Data System (ADS)

    Sramek, Christopher; Leung, Loh-Shan; Leng, Theodore; Brown, Jefferson; Paulus, Yannis M.; Schuele, Georg; Palanker, Daniel

    2011-02-01

    Decreasing the pulse duration helps confine damage, shorten treatment time, and minimize pain during retinal photocoagulation. However, the safe therapeutic window (TW), the ratio of threshold powers for thermomechanical rupture of Bruch's membrane and mild coagulation, also decreases with shorter exposures. Two potential approaches toward increasing TW are investigated: (a) decreasing the central irradiance of the laser beam and (b) temporally modulating the pulse. An annular beam with adjustable central irradiance was created by coupling a 532-nm laser into a 200-μm core multimode optical fiber at a 4-7 deg angle to normal incidence. Pulse shapes were optimized using a computational model, and a waveform generator was used to drive a PASCAL photocoagulator (532 nm), producing modulated laser pulses. Acute thresholds for mild coagulation and rupture were measured in Dutch-Belted rabbit in vivo with an annular beam (154-163 μm retinal diameter) and modulated pulse (132 μm, uniform irradiance ``flat-top'' beam) with 2-50 ms pulse durations. Thresholds with conventional constant-power pulse and a flat-top beam were also determined. Both annular beam and modulated pulse provided a 28% increase in TW at 10-ms duration, affording the same TW as 20-ms pulses with conventional parameters.

  1. Vitreal Oxygenation in Retinal Ischemia Reperfusion

    PubMed Central

    Abdallah, Walid; Ameri, Hossein; Barron, Ernesto; Chader, Gerald J.; Greenbaum, Elias; Hinton, David R.

    2011-01-01

    Purpose. To study the feasibility of anterior vitreal oxygenation for the treatment of acute retinal ischemia. Methods. Twenty rabbits were randomized into an oxygenation group, a sham treatment group, and a no treatment group. Baseline electroretinography (ERG) and preretinal oxygen (Po2) measurements were obtained 3 to 5 days before surgery. Intraocular pressure was raised to 100 mm Hg for 90 minutes and then normalized. The oxygenation group underwent vitreal oxygenation for 30 minutes using intravitreal electrodes. The sham treatment group received inactive electrodes for 30 minutes while there was no intervention for the no treatment group. Preretinal Po2 in the posterior vitreous was measured 30 minutes after intervention or 30 minutes after reperfusion (no treatment group) and on postoperative days (d) 3, 6, 9, and 12. On d14, rabbits underwent ERG and were euthanatized. Results. Mean final (d12) Po2 was 10.64 ± 0.77 mm Hg for the oxygenation group, 2.14 ± 0.61 mm Hg for the sham group, and 1.98 ± 0.63 mm Hg for the no treatment group. On ERG, scotopic b-wave amplitude was significantly preserved in the oxygenation group compared with the other two groups. Superoxide dismutase assay showed higher activity in the operated eyes than in the nonoperated control eyes in the sham treatment group and no treatment group only. Histopathology showed preservation of retinal architecture and choroidal vasculature in the oxygenation group, whereas the sham-treated and nontreated groups showed retinal thinning and choroidal atrophy. Conclusions. In severe total ocular ischemia, anterior vitreal oxygenation supplies enough oxygen to penetrate the retinal thickness, resulting in rescue of the RPE/choriocapillaris that continues to perfuse, hence sparing the retinal tissue from damage. PMID:21051734

  2. Quantitative analysis of retinal OCT.

    PubMed

    Sonka, Milan; Abràmoff, Michael D

    2016-10-01

    Clinical acceptance of 3-D OCT retinal imaging brought rapid development of quantitative 3-D analysis of retinal layers, vasculature, retinal lesions as well as facilitated new research in retinal diseases. One of the cornerstones of many such analyses is segmentation and thickness quantification of retinal layers and the choroid, with an inherently 3-D simultaneous multi-layer LOGISMOS (Layered Optimal Graph Image Segmentation for Multiple Objects and Surfaces) segmentation approach being extremely well suited for the task. Once retinal layers are segmented, regional thickness, brightness, or texture-based indices of individual layers can be easily determined and thus contribute to our understanding of retinal or optic nerve head (ONH) disease processes and can be employed for determination of disease status, treatment responses, visual function, etc. Out of many applications, examples provided in this paper focus on image-guided therapy and outcome prediction in age-related macular degeneration and on assessing visual function from retinal layer structure in glaucoma.

  3. Hospital Performance Indicators and Their Associated Factors in Acute Child Poisoning at a Single Poison Center, Central Saudi Arabia

    PubMed Central

    Alanazi, Menyfah Q.; Al-Jeriasy, Majed I.; Al-Assiri, Mohammed H.; Afesh, Lara Y.; Alhammad, Fahad; Salam, Mahmoud

    2015-01-01

    Abstract Admission rate and length of stay (LOS) are two hospital performance indicators that affect the quality of care, patients’ satisfaction, bed turnover, and health cost expenditures. The aim of the study was to identify factors associated with higher admission rates and extended average LOS among acutely poisoned children at a single poison center, central Saudi Arabia. This is a cross-sectional, poison and medical chart review between 2009 and 2011. Exposures were child characteristics, that is, gender, age, body mass index (BMI), health history, and Canadian 5-level triage scale. Poison incident characteristics were, that is, type, exposure route, amount, form, home remedy, and arrival time to center. Admission status and LOS were obtained from records. Chronic poisoning, plant allergies, and venomous bites were excluded. Bivariate and regression analyses were applied. Significance at P < 0.05. Of the 315 eligible cases, (72%) were toddlers with equal gender distribution, (58%) had normal BMI, and (77%) were previously healthy. Poison substances were pharmaceutical drugs (63%) versus chemical products (37%). Main exposure route was oral (98%). Home remedy was observed in (21.9%), which were fluids, solutes, and/or gag-induced vomiting. Almost (52%) arrived to center >1 h. Triage levels: non-urgent cases (58%), less urgent (11%), urgent (18%), emergency (12%), resuscitative (1%). Admission rate was (20.6%) whereas av. LOS was 13 ± 22 h. After adjusting and controlling for confounders, older children (adj.OR = 1.19) and more critical triage levels (adj.OR = 1.35) were significantly associated with higher admission rates compared to younger children and less critical triage levels (adj.P = 0.006) and (adj.P = 0.042) respectively. Home remedy prior arrival was significantly associated with higher av. LOS (Beta = 9.48, t = 2.99), compared to those who directly visited the center, adj.P = 0.003. Hospital administrators

  4. Electronic retinal implant surgery.

    PubMed

    MacLaren, R E

    2017-02-01

    Blindness due to outer retinal degeneration still remains largely untreatable. Photoreceptor loss removes light sensitivity, but the remaining inner retinal layers, the optic nerve, and indeed the physical structure of the eye itself may be unaffected by the degenerative processes. This provides the opportunity to restore some degree of vision with an electronic device in the subretinal space. In this lecture I will provide an overview of our experiences with the first-generation retinal implant Alpha IMS, developed by Retina Implant AG and based on the technology developed by Eberhart Zrenner as part of a multicentre clinical trial (NCT01024803). We are currently in the process of running a second NIHR-funded clinical trial to assess the next-generation device. The positive results from both studies to date indicate that the retinal implant should be included as a potential treatment for patients who are completely blind from retinitis pigmentosa. Evolution of the technology in future may provide further opportunities for earlier intervention or for other diseases.

  5. In Vivo Imaging of Retinal Hypoxia in a Model of Oxygen-Induced Retinopathy

    PubMed Central

    Uddin, Md. Imam; Evans, Stephanie M.; Craft, Jason R.; Capozzi, Megan E.; McCollum, Gary W.; Yang, Rong; Marnett, Lawrence J.; Uddin, Md. Jashim; Jayagopal, Ashwath; Penn, John S.

    2016-01-01

    Ischemia-induced hypoxia elicits retinal neovascularization and is a major component of several blinding retinopathies such as retinopathy of prematurity (ROP), diabetic retinopathy (DR) and retinal vein occlusion (RVO). Currently, noninvasive imaging techniques capable of detecting and monitoring retinal hypoxia in living systems do not exist. Such techniques would greatly clarify the role of hypoxia in experimental and human retinal neovascular pathogenesis. In this study, we developed and characterized HYPOX-4, a fluorescence-imaging probe capable of detecting retinal-hypoxia in living animals. HYPOX-4 dependent in vivo and ex vivo imaging of hypoxia was tested in a mouse model of oxygen-induced retinopathy (OIR). Predicted patterns of retinal hypoxia were imaged by HYPOX-4 dependent fluorescence activity in this animal model. In retinal cells and mouse retinal tissue, pimonidazole-adduct immunostaining confirmed the hypoxia selectivity of HYPOX-4. HYPOX-4 had no effect on retinal cell proliferation as indicated by BrdU assay and exhibited no acute toxicity in retinal tissue as indicated by TUNEL assay and electroretinography (ERG) analysis. Therefore, HYPOX-4 could potentially serve as the basis for in vivo fluorescence-based hypoxia-imaging techniques, providing a tool for investigators to understand the pathogenesis of ischemic retinopathies and for physicians to address unmet clinical needs. PMID:27491345

  6. Vitamin A Derivatives as Treatment Options for Retinal Degenerative Diseases

    PubMed Central

    Perusek, Lindsay; Maeda, Tadao

    2013-01-01

    The visual cycle is a sequential enzymatic reaction for vitamin A, all-trans-retinol, occurring in the outer layer of the human retina and is essential for the maintenance of vision. The central source of retinol is derived from dietary intake of both retinol and pro-vitamin A carotenoids. A series of enzymatic reactions, located in both the photoreceptor outer segment and the retinal pigment epithelium, transform retinol into the visual chromophore 11-cis-retinal, regenerating visual pigments. Retina specific proteins carry out the majority of the visual cycle, and any significant interruption in this sequence of reactions is capable of causing varying degrees of blindness. Among these important proteins are Lecithin:retinol acyltransferase (LRAT) and retinal pigment epithelium-specific 65-kDa protein (RPE65) known to be responsible for esterification of retinol to all-trans-retinyl esters and isomerization of these esters to 11-cis-retinal, respectively. Deleterious mutations in these genes are identified in human retinal diseases that cause blindness, such as Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). Herein, we discuss the pathology of 11-cis-retinal deficiency caused by these mutations in both animal disease models and human patients. We also review novel therapeutic strategies employing artificial visual chromophore 9-cis-retinoids which have been employed in clinical trials involving LCA patients. PMID:23857173

  7. Retinal and visual system: occupational and environmental toxicology.

    PubMed

    Fox, Donald A

    2015-01-01

    Occupational chemical exposure often results in sensory systems alterations that occur without other clinical signs or symptoms. Approximately 3000 chemicals are toxic to the retina and central visual system. Their dysfunction can have immediate, long-term, and delayed effects on mental health, physical health, and performance and lead to increased occupational injuries. The aims of this chapter are fourfold. First, provide references on retinal/visual system structure, function, and assessment techniques. Second, discuss the retinal features that make it especially vulnerable to toxic chemicals. Third, review the clinical and corresponding experimental data regarding retinal/visual system deficits produced by occupational toxicants: organic solvents (carbon disulfide, trichloroethylene, tetrachloroethylene, styrene, toluene, and mixtures) and metals (inorganic lead, methyl mercury, and mercury vapor). Fourth, discuss occupational and environmental toxicants as risk factors for late-onset retinal diseases and degeneration. Overall, the toxicants altered color vision, rod- and/or cone-mediated electroretinograms, visual fields, spatial contrast sensitivity, and/or retinal thickness. The findings elucidate the importance of conducting multimodal noninvasive clinical, electrophysiologic, imaging and vision testing to monitor toxicant-exposed workers for possible retinal/visual system alterations. Finally, since the retina is a window into the brain, an increased awareness and understanding of retinal/visual system dysfunction should provide additional insight into acquired neurodegenerative disorders.

  8. A continuum model of retinal electrical stimulation

    NASA Astrophysics Data System (ADS)

    Joarder, Saiful A.; Abramian, Miganoosh; Suaning, Gregg J.; Lovell, Nigel H.; Dokos, Socrates

    2011-10-01

    A continuum mathematical model of retinal electrical stimulation is described. The model is represented by a passive vitreous domain, a thin layer of active retinal ganglion cell (RGC) tissue adjacent to deeper passive neural layers of the retina, the retinal pigmented epithelium (RPE) and choroid thus ending at the sclera. To validate the model, in vitro epiretinal responses to stimuli from 50 µm disk electrodes, arranged in a hexagonal mosaic, were recorded from rabbit retinas. 100 µs/phase anodic-first biphasic current pulses were delivered to the retinal surface in both the mathematical model and experiments. RGC responses were simulated and recorded using extracellular microelectrodes. The model's epiretinal thresholds compared favorably with the in vitro data. In addition, simulations showed that single-return bipolar electrodes recruited a larger area of the retina than twin-return or six-return electrodes arranged in a hexagonal layout in which a central stimulating electrode is surrounded by six, eqi-spaced returns. Simulations were also undertaken to investigate the patterns of RGC activation in an anatomically-accurate model of the retina, as well as RGC activation patterns for subretinal and suprachoroidal bipolar stimulation. This paper was originally submitted for the special issue containing contributions from the Sixth Biennial Research Congress of The Eye and the Chip.

  9. Probabilistic retinal vessel segmentation

    NASA Astrophysics Data System (ADS)

    Wu, Chang-Hua; Agam, Gady

    2007-03-01

    Optic fundus assessment is widely used for diagnosing vascular and non-vascular pathology. Inspection of the retinal vasculature may reveal hypertension, diabetes, arteriosclerosis, cardiovascular disease and stroke. Due to various imaging conditions retinal images may be degraded. Consequently, the enhancement of such images and vessels in them is an important task with direct clinical applications. We propose a novel technique for vessel enhancement in retinal images that is capable of enhancing vessel junctions in addition to linear vessel segments. This is an extension of vessel filters we have previously developed for vessel enhancement in thoracic CT scans. The proposed approach is based on probabilistic models which can discern vessels and junctions. Evaluation shows the proposed filter is better than several known techniques and is comparable to the state of the art when evaluated on a standard dataset. A ridge-based vessel tracking process is applied on the enhanced image to demonstrate the effectiveness of the enhancement filter.

  10. Retinoids and Retinal Diseases

    PubMed Central

    Kiser, Philip D.; Palczewski, Krzysztof

    2016-01-01

    Recent progress in molecular understanding of the retinoid cycle in mammalian retina stems from painstaking biochemical reconstitution studies supported by natural or engineered animal models with known genetic lesions and studies of humans with specific genetic blinding diseases. Structural and membrane biology have been used to detect critical retinal enzymes and proteins and their substrates and ligands, placing them in a cellular context. These studies have been supplemented by analytical chemistry methods that have identified small molecules by their spectral characteristics, often in conjunction with the evaluation of models of animal retinal disease. It is from this background that rational therapeutic interventions to correct genetic defects or environmental insults are identified. Thus, most presently accepted modulators of the retinoid cycle already have demonstrated promising results in animal models of retinal degeneration. These encouraging signs indicate that some human blinding diseases can be alleviated by pharmacological interventions. PMID:27917399

  11. Bioelectronic retinal prosthesis

    NASA Astrophysics Data System (ADS)

    Weiland, James D.

    2016-05-01

    Retinal prosthesis have been translated to clinical use over the past two decades. Currently, two devices have regulatory approval for the treatment of retinitis pigmentosa and one device is in clinical trials for treatment of age-related macular degeneration. These devices provide partial sight restoration and patients use this improved vision in their everyday lives to navigate and to detect large objects. However, significant vision restoration will require both better technology and improved understanding of the interaction between electrical stimulation and the retina. In particular, current retinal prostheses do not provide peripheral visions due to technical and surgical limitations, thus limiting the effectiveness of the treatment. This paper reviews recent results from human implant patients and presents technical approaches for peripheral vision.

  12. Automatic Retinal Oximetry

    NASA Astrophysics Data System (ADS)

    Halldorsson, G. H.; Karlsson, R. A.; Hardarson, S. H.; Mura, M. Dalla; Eysteinsson, T.; Beach, J. M.; Stefansson, E.; Benediktsson, J. A.

    2007-10-01

    This paper presents a method for automating the evaluation of hemoglobin oxygen saturation in the retina. This method should prove useful for monitoring ischemic retinal diseases and the effect of treatment. In order to obtain saturation values automatically, spectral images must be registered in pairs, the vessels of the retina located and measurement points must be selected. The registration algorithm is based on a data driven approach that circumvents many of the problems that have plagued previous methods. The vessels are extracted using an algorithm based on morphological profiles and supervised classifiers. Measurement points on retinal arterioles and venules as well as reference points on the adjacent fundus are automatically selected. Oxygen saturation values along vessels are averaged to arrive at a more accurate estimate of the retinal vessel oxygen saturation. The system yields reproducible results as well as being sensitive to changes in oxygen saturation.

  13. Retinal Failure in Diabetes: a Feature of Retinal Sensory Neuropathy.

    PubMed

    Gray, Ellyn J; Gardner, Thomas W

    2015-12-01

    Physiologic adaptations mediate normal responses to short-term and long-term stresses to ensure organ function. Organ failure results if adaptive responses fail to resolve persistent stresses or maladaptive reactions develop. The retinal neurovascular unit likewise undergoes adaptive responses to diabetes resulting in a retinal sensory neuropathy analogous to other sensory neuropathies. Vision-threatening diabetic retinal neuropathy results from unremitting metabolic and inflammatory stresses, leading to macular edema and proliferative diabetic retinopathy, states of "retinal failure." Current regulatory strategies focus primarily on the retinal failure stages, but new diagnostic modalities and understanding of the pathophysiology of diabetic retinopathy may facilitate earlier treatment to maintain vision in persons with diabetes.

  14. Outcomes and Acute Toxicities of Proton Therapy for Pediatric Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System

    SciTech Connect

    McGovern, Susan L.; Okcu, M. Fatih; Munsell, Mark F.; Kumbalasseriyil, Nancy; Grosshans, David R.; McAleer, Mary F.; Chintagumpala, Murali; Khatua, Soumen; Mahajan, Anita

    2014-12-01

    Purpose: Atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system is a rare cancer primarily affecting children younger than 5 years old. Because patients are young and receive intensive chemotherapy, there is concern regarding late radiation toxicity, particularly as survival rates improve. Therefore, there is interest in using proton therapy to treat these tumors. This study was undertaken to investigate outcomes and acute toxicities associated with proton therapy for AT/RT. Methods and Materials: The records of 31 patients with AT/RT treated with proton radiation from October 2008 to August 2013 were reviewed. Demographics, treatment characteristics, and outcomes were recorded and analyzed. Results: Median age at diagnosis was 19 months (range, 4-55 months), with a median age at radiation start of 24 months (range, 6-62 months). Seventeen patients received local radiation with a median dose of 50.4 GyRBE (range, 9-54 GyRBE). Fourteen patients received craniospinal radiation; half received 24 GyRBE or less, and half received 30.6 GyRBE or more. For patients receiving craniospinal radiation, the median tumor dose was 54 GyRBE (range, 43.2-55.8 GyRBE). Twenty-seven patients (87%) completed the planned radiation. With median follow-up of 24 months for all patients (range, 3-53 months), median progression-free survival was 20.8 months and median overall survival was 34.3 months. Five patients (16%) developed clinical findings and imaging changes in the brainstem 1 to 4 months after radiation, consistent with radiation reaction; all cases resolved with steroids or bevacizumab. Conclusions: This is the largest report of children with AT/RT treated with proton therapy. Preliminary survival outcomes in this young pediatric population are encouraging compared to historic results, but further study is warranted.

  15. Acute Effect of Central Administration of Urotensin II on Baroreflex and Blood Pressure in Conscious Normotensive Rabbits

    PubMed Central

    Lim, Kyungjoon; Sata, Yusuke; Jackson, Kristy L.; Burke, Sandra L.; Head, Geoffrey A.

    2017-01-01

    In the present study, we examined the effects of central administration of Urotensin II on blood pressure, heart rate, and baroreceptor heart rate reflexes in conscious normotensive rabbits. Preliminary operations were undertaken to implant a balloon cuff on the inferior vena cava for baroreflex assessments and to implant cannula into the lateral and fourth ventricle. After 2 weeks of recovery cumulative dose response curves to Urotensin II (10, 100 ng, 1, 10, and 100 μg) given into the ventricles, or Ringer's solution as a vehicle were performed on separate days. Injections were given each hour and baroreflex assessments were made 30 min after each administration. Analysis of the dose response curves to Urotensin II compared to vehicle administered into the lateral or fourth ventricle, indicated little change to blood pressure or heart rate. Analysis of the time course to the highest dose over a 30 min period revealed a small (−5 mmHg) depressor response maximal at 10 min when injected into the fourth ventricle but no effect when injected into the lateral ventricle. Baroreflex assessments made at each dose showed that there was no change in baroreflex sensitivity but that an increase in the upper plateau was observed when Urotensin was injected into the lateral ventricle and a tendency for a reduced lower heart rate plateau was observed after fourth ventricle administration. Clonidine administration in the fourth ventricle decreased blood pressure and heart rate, thus confirming catheter patency. In conclusion, our findings suggest that Urotensin II in the forebrain and brainstem may play a role in modulating cardiac sympathetic and vagal baroreflexes but only during large acute changes in blood pressure. PMID:28280470

  16. The rat acute-phase protein α2-macroglobulin plays a central role in amifostine-mediated radioprotection.

    PubMed

    Mirjana, Mihailović; Goran, Poznanović; Nevena, Grdović; Melita, Vidaković; Svetlana, Dinić; Ilijana, Grigorov; Desanka, Bogojević

    2010-09-01

    Previously we reported that elevated circulating concentrations of the acute-phase (AP) protein α(2)-macroglobulin (α(2)M), either as typically occurring in pregnant female rats or after administration to male rats, provides radioprotection, displayed as 100% survival of experimental animals exposed to total-body irradiation with 6.7 Gy (LD(50/30)) x-rays, that is as effective as that afforded by the synthetic radioprotector amifostine. The finding that amifostine administration induces a 45-fold increase in α(2)M in the circulation led us to hypothesise that α(2)M assumes an essential role in both natural and amifostine-mediated radioprotection in the rat. In the present work we examined the activation of cytoprotective mechanisms in rat hepatocytes after the exogenous administration of α(2)M and amifostine. Our results showed that the IL6/JAK/STAT3 hepatoprotective signal pathway, described in a variety of liver-injury models, upregulated the α(2)M gene in amifostine-pretreated animals. In both α(2)M- and amifostine-pretreated rats we observed the activation of the Akt signalling pathways that mediate cellular survival. At the cellular level this was reflected as a significant reduction of irradiation-induced DNA damage that allowed for the rapid and complete restoration of liver mass and ultimately at the level of the whole organism the complete restoration of body weight. We conclude that the selective upregulation of α(2)M plays a central role in amifostine-provided radioprotection.

  17. Pathway to Retinal Oximetry

    PubMed Central

    Beach, James

    2014-01-01

    Events and discoveries in oxygen monitoring over the past two centuries are presented as the background from which oximetry of the human retina evolved. Achievements and the people behind them are discussed, showing parallels between the work in tissue measurements and later in the eye. Developments in the two-wavelength technique for oxygen saturation measurements in retinal vessels are shown to exploit the forms of imaging technology available over time. The last section provides a short summary of the recent research in retinal diseases using vessel oximetry. PMID:25237591

  18. Hereditary Retinal Dystrophy.

    PubMed

    Hohman, Thomas C

    2016-12-30

    As our understanding of the genetic basis for inherited retinal disease has expanded, gene therapy has advanced into clinical development. When the gene mutations associated with inherited retinal dystrophies were identified, it became possible to create animal models in which individual gene were altered to match the human mutations. The retina of these animals were then characterized to assess whether the mutated genes produced retinal phenotypes characteristic of disease-affected patients. Following the identification of a subpopulation of patients with the affected gene and the development of techniques for the viral gene transduction of retinal cells, it has become possible to deliver a copy of the normal gene into the retinal sites of the mutated genes. When this was performed in animal models of monogenic diseases, at an early stage of retinal degeneration when the affected cells remained viable, successful gene augmentation corrected the structural and functional lesions characteristic of the specific diseases in the areas of the retina that were successfully transduced. These studies provided the essential proof-of-concept needed to advance monogenic gene therapies into clinic development; these therapies include treatments for: Leber's congenital amaurosis type 2, caused by mutations to RPE65, retinoid isomerohydrolase; choroideremia, caused by mutations to REP1, Rab escort protein 1; autosomal recessive Stargardt disease, caused by mutations to ABCA4, the photoreceptor-specific ATP-binding transporter; Usher 1B disease caused by mutations to MYO7A, myosin heavy chain 7; X-linked juvenile retinoschisis caused by mutations to RS1, retinoschisin; autosomal recessive retinitis pigmentosa caused by mutations to MERTK, the proto-oncogene tyrosine-protein kinase MER; Leber's hereditary optic neuropathy caused by mutations to ND4, mitochondrial nicotinamide adenine dinucleotide ubiquinone oxidoreductase (complex I) subunit 4 and achromatopsia, caused by

  19. Pathway to Retinal Oximetry.

    PubMed

    Beach, James

    2014-09-01

    Events and discoveries in oxygen monitoring over the past two centuries are presented as the background from which oximetry of the human retina evolved. Achievements and the people behind them are discussed, showing parallels between the work in tissue measurements and later in the eye. Developments in the two-wavelength technique for oxygen saturation measurements in retinal vessels are shown to exploit the forms of imaging technology available over time. The last section provides a short summary of the recent research in retinal diseases using vessel oximetry.

  20. Retinal compensatory changes after light damage in albino mice

    PubMed Central

    Montalbán-Soler, Luis; Alarcón-Martínez, Luis; Jiménez-López, Manuel; Salinas-Navarro, Manuel; Galindo-Romero, Caridad; Bezerra de Sá, Fabrízio; García-Ayuso, Diego; Avilés-Trigueros, Marcelino; Vidal-Sanz, Manuel; Agudo-Barriuso, Marta

    2012-01-01

    Purpose To investigate the anatomic and functional changes triggered by light exposure in the albino mouse retina and compare them with those observed in the albino rat. Methods BALB/c albino mice were exposed to 3,000 lx of white light during 24 h and their retinas analyzed from 1 to 180 days after light exposure (ALE). Left pupil mydriasis was induced with topical atropine. Retinal function was analyzed by electroretinographic (ERG) recording. To assess retinal degeneration, hematoxylin and eosin staining, the TdT-mediated dUTP nick-end labeling (TUNEL) technique, and quantitative immunohistofluorescence for synaptophysin and protein kinase Cα (PKCα) were used in cross sections. Intravenous injection of horseradish peroxidase and Fluoro-Gold™ tracing were used in whole-mounted retinas to study the retinal vasculature and the retinal ganglion cell (RGC) population, respectively. Results Light exposure caused apoptotic photoreceptor death in the central retina. This death was more severe in the dorsal than in the ventral retina, sparing the periphery. Neither retinal vascular leakage nor retinal ganglion cell death was observed ALE. The electroretinographic a-wave was permanently impaired, while the b-wave decreased but recovered gradually by 180 days ALE. The scotopic threshold responses, associated with the inner retinal function, diminished at first but recovered completely by 14 days ALE. This functional recovery was concomitant with the upregulation of protein kinase Cα and synaptophysin. Similar results were obtained in both eyes, irrespective of mydriasis. Conclusions In albino mice, light exposure induces substantial retinal damage, but the surviving photoreceptors, together with compensatory morphological/molecular changes, allow an important restoration of the retinal function. PMID:22509098

  1. Macular pigment optical density is related to serum lutein in retinitis pigmentosa

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Purpose: To determine whether macular pigment optical density (MPOD) is related to the degree of cystoid macular edema (CME) in patients with retinitis pigmentosa. Methods: We measured MPOD with heterochromatic flicker photometry and central foveal retinal thickness with optical coherence tomography...

  2. AMIGO3 is an NgR1/p75 co-receptor signalling axon growth inhibition in the acute phase of adult central nervous system injury.

    PubMed

    Ahmed, Zubair; Douglas, Michael R; John, Gabrielle; Berry, Martin; Logan, Ann

    2013-01-01

    Axon regeneration in the injured adult CNS is reportedly inhibited by myelin-derived inhibitory molecules, after binding to a receptor complex comprised of the Nogo-66 receptor (NgR1) and two transmembrane co-receptors p75/TROY and LINGO-1. However, the post-injury expression pattern for LINGO-1 is inconsistent with its proposed function. We demonstrated that AMIGO3 levels were significantly higher acutely than those of LINGO-1 in dorsal column lesions and reduced in models of dorsal root ganglion neuron (DRGN) axon regeneration. Similarly, AMIGO3 levels were raised in the retina immediately after optic nerve crush, whilst levels were suppressed in regenerating optic nerves, induced by intravitreal peripheral nerve implantation. AMIGO3 interacted functionally with NgR1-p75/TROY in non-neuronal cells and in brain lysates, mediating RhoA activation in response to CNS myelin. Knockdown of AMIGO3 in myelin-inhibited adult primary DRG and retinal cultures promoted disinhibited neurite growth when cells were stimulated with appropriate neurotrophic factors. These findings demonstrate that AMIGO3 substitutes for LINGO-1 in the NgR1-p75/TROY inhibitory signalling complex and suggests that the NgR1-p75/TROY-AMIGO3 receptor complex mediates myelin-induced inhibition of axon growth acutely in the CNS. Thus, antagonizing AMIGO3 rather than LINGO-1 immediately after CNS injury is likely to be a more effective therapeutic strategy for promoting CNS axon regeneration when combined with neurotrophic factor administration.

  3. Retinal Waves Modulate an Intraretinal Circuit of Intrinsically Photosensitive Retinal Ganglion Cells

    PubMed Central

    Arroyo, David A.; Kirkby, Lowry A.

    2016-01-01

    Before the maturation of rod and cone photoreceptors, the developing retina relies on light detection by intrinsically photosensitive retinal ganglion cells (ipRGCs) to drive early light-dependent behaviors. ipRGCs are output neurons of the retina; however, they also form functional microcircuits within the retina itself. Whether ipRGC microcircuits exist during development and whether they influence early light detection remain unknown. Here, we investigate the neural circuit that underlies the ipRGC-driven light response in developing mice. We use a combination of calcium imaging, tracer coupling, and electrophysiology experiments to show that ipRGCs form extensive gap junction networks that strongly contribute to the overall light response of the developing retina. Interestingly, we found that gap junction coupling was modulated by spontaneous retinal waves, such that acute blockade of waves dramatically increased the extent of coupling and hence increased the number of light-responsive neurons. Moreover, using an optical sensor, we found that this wave-dependent modulation of coupling is driven by dopamine that is phasically released by retinal waves. Our results demonstrate that ipRGCs form gap junction microcircuits during development that are modulated by retinal waves; these circuits determine the extent of the light response and thus potentially impact the processing of early visual information and light-dependent developmental functions. SIGNIFICANCE STATEMENT Light-dependent functions in early development are mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs). Here we show that ipRGCs form an extensive gap junction network with other retinal neurons, including other ipRGCs, which shapes the retina's overall light response. Blocking cholinergic retinal waves, which are the primary source of neural activity before maturation of photoreceptors, increased the extent of ipRGC gap junction networks, thus increasing the number of light

  4. Nanomaterials and Retinal Toxicity

    EPA Science Inventory

    The neuroretina should be considered as a potential site of nanomaterial toxicity. Engineered nanomaterials may reach the retina through three potential routes of exposure including; intra­ vitreal injection of therapeutics; blood-borne delivery in the retinal vasculature an...

  5. Retinal Vasculitis in Anti-Synthetase Syndrome.

    PubMed

    Donovan, Christopher P; Pecen, Paula E; Baynes, Kimberly; Ehlers, Justis P; Srivastava, Sunil K

    2016-09-01

    A 31-year-old woman with a history of anti-synthetase syndrome-related myositis and interstitial lung disease presented with acute-onset blurry vision and rash on her hands and feet. Visual acuity was hand motion in her right eye and 20/40 in her left eye. Dilated fundus exam showed extensive retinal vasculitis, diffuse intraretinal hemorrhages, and subretinal fluid. Optical coherence tomography revealed significant macular thickening, and fluorescein angiography revealed vascular leakage with peripheral nonperfusion. Aggressive systemic immunosuppression was initiated, with gradual resolution of her disease during 8 months of follow-up. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:874-879.].

  6. Unilateral Ischemic Maculopathy Associated with Cytomegalovirus Retinitis in Patients with AIDS: Optical Coherence Tomography Findings

    PubMed Central

    Arevalo, J. Fernando; Garcia, Reinaldo A.; Arevalo, Fernando A.; Fernandez, Carlos F.

    2015-01-01

    To describe the clinical and optical coherence tomography (OCT) characteristics of ischemic maculopathy in two patients with acquired immunodeficiency syndrome (AIDS). Two patients with AIDS and cytomegalovirus (CMV) retinitis developed ischemic maculopathy. Both patients presented with central visual loss and active granular CMV retinitis. The presence of opacification of the superficial retina in the macular area and intraretinal edema suggested the diagnosis. Fluorescein angiography changes were similar in the two cases with enlargement of the foveal avascular zone and late staining of juxtafoveal vessels. OCT changes were suggestive of retinal ischemia: Increased reflectivity from the inner retinal layer and decreased backscattering from the retinal photoreceptors due to fluid and retinal edema. Ischemic maculopathy may cause a severe and permanent decrease in vision in AIDS patients. Fluorescein angiography and OCT should be considered in any patient with AIDS and unexplained visual loss. The mechanism of ischemic maculopathy may be multifactorial. PMID:27051496

  7. Comparison of central nervous system prophylaxis with cranial radiation and intrathecal methotrexate versus intrathecal methotrexate alone in acute lymphoblastic leukemia

    SciTech Connect

    Muriel, F.S.; Svarch, E.; Pavlovsky, S.; Eppinger-Helft, M.; Braier, J.; Vergara, B.; Garay, G.; Kvicala, R.; Divito, J.M.; Failace, R.

    1983-08-01

    In acute lymphoblastic leukemia, central nervous system prophylaxis with irradiation plus intrathecal methotrexate (i.t. MTX) reduces the incidence of CNS relapse to 7%-15%. However, increased evidence of CNS delayed toxicity was recognized mainly in children as CT scan abnormalities and neuropsychologic alterations. Two questions were analyzed: (1) Will further doses of i.t. methotraxate and dexamethasone (i.t. MTX-DMT) decrease the incidence of CNS relapse. (2) Is i.t. MTX-DMT given during induction and maintenance as effective as cranium irradiation plus i.t. MTX-DMT. Incidence of primary CNS relapse in i.t. MTX-DMT-treated patients with a WBC count < 50,000 and in the untreated group was 11%. In patients with a WBC count > 50,000, it was 16% in the treated group and 19% in the control group. These patients were compared with patients which had received 3 doses of i.t. MTX-DMT alone during induction, 3 doses weekly during the first month of remission, and quarterly thereafter. The incidence of leukemia at 60 mo in patients with a WBC count < 50,000 was 20% in the irradiated group and 32% in the group with i.t. MTX-DMT alone. The relapse-free survival at 60 mo was 26% and 41%, respectively, (p < 0.0005). The incidence in patients with a WBC count > 50,000 at 48 mo was 28% and 42% in the irradiated and nonirradiated group respectively. Complete remission remained at 15% and 16% respectively of patients disease-free at 48 mo. We conclude that (A) after cranial irradiation plus i.t. MTX-DMT X 5, the use of additional doses of i.t. MTX-DMT is not of further benefit in preventing CNS relapse; (B) use of i.t. MTX-DMT alone compares with cranial irradiation plus i.t. MTX-DMT in incidence of CNS relapse; and (C) relapse-free survival and survival in patients with a WBC count < 50.000 were significantly longer in those without cranial irradiation.

  8. Histone Deacetylase Inhibition Restores Retinal Pigment Epithelium Function in Hyperglycemia

    PubMed Central

    Desjardins, Danielle; Liu, Yueying; Crosson, Craig E.; Ablonczy, Zsolt

    2016-01-01

    In diabetic individuals, macular edema is a major cause of vision loss. This condition is refractory to insulin therapy and has been attributed to metabolic memory. The retinal pigment epithelium (RPE) is central to maintaining fluid balance in the retina, and this function is compromised by the activation of advanced glycation end-product receptors (RAGE). Here we provide evidence that acute administration of the RAGE agonist, glycated-albumin (gAlb) or vascular endothelial growth factor (VEGF), increased histone deacetylase (HDAC) activity in RPE cells. The administration of the class I/II HDAC inhibitor, trichostatin-A (TSA), suppressed gAlb-induced reductions in RPE transepithelial resistance (in vitro) and fluid transport (in vivo). Systemic TSA also restored normal RPE fluid transport in rats with subchronic hyperglycemia. Both gAlb and VEGF increased HDAC activity and reduced acetyl-α-tubulin levels. Tubastatin-A, a relatively specific antagonist of HDAC6, inhibited gAlb-induced changes in RPE cell resistance. These data are consistent with the idea that RPE dysfunction following exposure to gAlb, VEGF, or hyperglycemia is associated with increased HDAC6 activity and decreased acetyl-α-tubulin. Therefore, we propose inhibiting HDAC6 in the RPE as a potential therapy for preserving normal fluid homeostasis in the hyperglycemic retina. PMID:27617745

  9. Progressive outer retinal necrosis syndrome in the course of systemic lupus erythematosus.

    PubMed

    Turno-Kręcicka, A; Tomczyk-Socha, M; Zimny, A

    2016-12-01

    Progressive outer retinal necrosis syndrome (PORN) is a severe clinical variant of necrotizing herpetic chorioretinitis, which occurs almost exclusively in patients with advanced acquired immunodeficiency syndrome (AIDS). To date, only a few cases of PORN have been reported in patients, mostly among those who were immunocompromised. To our knowledge, only one case of PORN in a patient with systemic lupus erythematosus (SLE) has been described. We report the case of a 44-year old HIV-negative patient with lupus nephritis, whom was being treated by mycophenolate mophetil (MMF), arechin and prednisone. After 14 months of MMF therapy, the patient revealed PORN symptoms; and several months later, the patient developed Type B primary central nervous system lymphoma (PCNSL). PORN is usually compared to acute retinal necrosis (ARN) syndrome, because of having the same causative agent: varicella zoster virus (VZV). There are also some similarities in clinical findings. Our observation supports the hypothesis that PORN symptoms in HIV-negative patients can be an intermediate form between ARN and PORN, and can vary according to the patient's immune status.

  10. Sex steroids inhibit osmotic swelling of retinal glial cells.

    PubMed

    Neumann, Florian; Wurm, Antje; Linnertz, Regina; Pannicke, Thomas; Iandiev, Ianors; Wiedemann, Peter; Reichenbach, Andreas; Bringmann, Andreas

    2010-04-01

    Osmotic swelling of glial cells may contribute to the development of retinal edema. We investigated whether sex steroids inhibit the swelling of glial somata in acutely isolated retinal slices and glial cells of the rat. Superfusion of retinal slices or cells from control animals with a hypoosmolar solution did not induce glial swelling, whereas glial swelling was observed in slices of postischemic and diabetic retinas. Progesterone, testosterone, estriol, and 17beta-estradiol prevented glial swelling with half-maximal effects at approximately 0.3, 0.6, 6, and 20 microM, respectively. The effect of progesterone was apparently mediated by transactivation of metabotropic glutamate receptors, P2Y1, and adenosine A1 receptors. The data suggest that sex steroids may inhibit cytotoxic edema in the retina.

  11. Molecular Pathogenesis of Retinal and Choroidal Vascular Diseases

    PubMed Central

    Campochiaro, Peter A.

    2015-01-01

    There are two major types of ocular neovascularization that affect the retina, retinal neovascularization (NV) and subretinal or choroidal NV. Retinal NV occurs in a group of diseases referred to as ischemic retinopathies in which damage to retinal vessels results in retinal ischemia. Most prevalent of these are diabetic retinopathy and retinal vein occlusions. Subretinal and choroidal NV occur in diseases of the outer retina and Bruch’s membrane, the most prevalent of which is age-related macular degeneration. Numerous studies in mouse models have helped to elucidate the molecular pathogenesis underlying retinal, subretinal, and choroidal NV. There is considerable overlap because the precipitating event in each is stabilization of hypoxia inducible factor-1 (HIF-1) which leads to upregulation of several hypoxia-regulated gene products, including vascular endothelial growth factor (VEGF), angiopoietin 2, vascular endothelial-protein tyrosine phosphatase (VE-PTP), and several others. Stimulation of VEGF signaling and suppression of Tie2 by angiopoietin 2 and VE-PTP are critical for sprouting of retinal, subretinal, and choroidal NV, with perturbation of Bruch’s membrane also needed for the latter. Additional HIF-1-regulated gene products cause further stimulation of the NV. It is difficult to model macular edema in animals and therefore proof-of-concept clinical trials were done and demonstrated that VEGF plays a central role and that suppression of Tie2 is also important. Neutralization of VEGF is currently the first line therapy for all of the above disease processes, but new treatments directed at some of the other molecular targets, particularly stabilization of Tie2, are likely to provide additional benefit for subretinal/choroidal NV and macular edema. In addition, the chronicity of these diseases as well as the implication of VEGF as a cause of retinal nonperfusion and progression of background diabetic retinopathy make sustained delivery approaches for

  12. Small Animal Retinal Imaging

    NASA Astrophysics Data System (ADS)

    Choi, WooJhon; Drexler, Wolfgang; Fujimoto, James G.

    Developing and validating new techniques and methods for small animal imaging is an important research area because there are many small animal models of retinal diseases such as diabetic retinopathy, age-related macular degeneration, and glaucoma [1-6]. Because the retina is a multilayered structure with distinct abnormalities occurring in different intraretinal layers at different stages of disease progression, there is a need for imaging techniques that enable visualization of these layers individually at different time points. Although postmortem histology and ultrastructural analysis can be performed for investigating microscopic changes in the retina in small animal models, this requires sacrificing animals, which makes repeated assessment of the same animal at different time points impossible and increases the number of animals required. Furthermore, some retinal processes such as neurovascular coupling cannot be fully characterized postmortem.

  13. Massive Bilateral Serous Retinal Detachment in a Case of Hypertensive Chorioretinopathy

    PubMed Central

    Villalba-Pinto, Luis; Hernández-Ortega, M. Ángeles; de los Mozos, F. Javier Lavid; Pascual-Camps, Isabel; Dolz-Marco, Rosa; Arevalo, J. Fernando; Gallego-Pinazo, Roberto

    2014-01-01

    Introduction Systemic high blood pressure is related to a variety of retinal manifestations. We present an atypical case of hypertensive chorioretinopathy with massive bilateral serous retinal detachment. Case Report A 26-year-old male with a genitourinary malformation and secondary grade IV chronic kidney failure as well as high blood pressure complained of acute vision loss. Dilated fundus examination evidenced a bilateral serous retinal detachment with macular involvement. The patient was unresponsive to oral antihypertensive therapy and dialysis treatment. The serous retinal detachment progressively decreased after the restoration of dialysis and antihypertensive therapy. The final visual acuity was 0.50 in both eyes. Discussion In cases of serous macular detachment, it is mandatory to rule out different systemic and ocular diseases. The presence of uncontrolled high blood pressure may produce aggressive bilateral retinal changes, thus hypertension must be under early and strict control in order to improve the visual outcomes. PMID:25120474

  14. Inherited Retinal Degenerative Disease Registry

    ClinicalTrials.gov

    2016-03-21

    Eye Diseases Hereditary; Retinal Disease; Achromatopsia; Bardet-Biedl Syndrome; Bassen-Kornzweig Syndrome; Batten Disease; Best Disease; Choroidal Dystrophy; Choroideremia; Cone Dystrophy; Cone-Rod Dystrophy; Congenital Stationary Night Blindness; Enhanced S-Cone Syndrome; Fundus Albipunctatus; Goldmann-Favre Syndrome; Gyrate Atrophy; Juvenile Macular Degeneration; Kearns-Sayre Syndrome; Leber Congenital Amaurosis; Refsum Syndrome; Retinitis Pigmentosa; Retinitis Punctata Albescens; Retinoschisis; Rod-Cone Dystrophy; Rod Dystrophy; Rod Monochromacy; Stargardt Disease; Usher Syndrome

  15. Glutamatergic Retinal Waves

    PubMed Central

    Kerschensteiner, Daniel

    2016-01-01

    Spontaneous activity patterns propagate through many parts of the developing nervous system and shape the wiring of emerging circuits. Prior to vision, waves of activity originating in the retina propagate through the lateral geniculate nucleus (LGN) of the thalamus to primary visual cortex (V1). Retinal waves have been shown to instruct the wiring of ganglion cell axons in LGN and of thalamocortical axons in V1 via correlation-based plasticity rules. Across species, retinal waves mature in three stereotypic stages (I–III), in which distinct circuit mechanisms give rise to unique activity patterns that serve specific functions in visual system refinement. Here, I review insights into the patterns, mechanisms, and functions of stage III retinal waves, which rely on glutamatergic signaling. As glutamatergic waves spread across the retina, neighboring ganglion cells with opposite light responses (ON vs. OFF) are activated sequentially. Recent studies identified lateral excitatory networks in the inner retina that generate and propagate glutamatergic waves, and vertical inhibitory networks that desynchronize the activity of ON and OFF cells in the wavefront. Stage III wave activity patterns may help segregate axons of ON and OFF ganglion cells in the LGN, and could contribute to the emergence of orientation selectivity in V1. PMID:27242446

  16. Novel Genetic Loci Associated with Retinal Microvascular Diameter

    PubMed Central

    Jensen, Richard A.; Sim, Xueling; Smith, Albert Vernon; Li, Xiaohui; Jakobsdóttir, Jóhanna; Cheng, Ching-Yu; Brody, Jennifer A.; Cotch, Mary Frances; Mcknight, Barbara; Klein, Ronald; Wang, Jie Jin; Kifley, Annette; Harris, Tamara B.; Launer, Lenore J.; Taylor, Kent D.; Klein, Barbara E.K.; Raffel, Leslie J.; Li, Xiang; Ikram, M. Arfan; Klaver, Caroline C.; van der Lee, Sven J.; Mutlu, Unal; Hofman, Albert; Uitterlinden, Andre G.; Liu, Chunyu; Kraja, Aldi T.; Mitchell, Paul; Gudnason, Vilmundur; Rotter, Jerome I.; Boerwinkle, Eric; van Duijn, Cornelia M.; Psaty, Bruce M.; Wong, Tien Y.

    2015-01-01

    Background There is increasing evidence that retinal microvascular diameters are associated with cardio- and cerebrovascular conditions. The shared genetic effects of these associations are currently unknown. The aim of this study was to increase our understanding of the genetic factors that mediate retinal vessel size. Methods and Results This study extends previous genome-wide association study results using 24,000+ multi-ethnic participants from 7 discovery and 5,000+ subjects of European ancestry from 2 replication cohorts. Using the Illumina HumanExome BeadChip, we investigate the association of single nucleotide polymorphisms (SNPs) and variants collectively across genes with summary measures of retinal vessel diameters, referred to as the central retinal venule equivalent (CRVE) and the central retinal arteriole equivalent (CRAE). We report 4 new loci associated with CRVE, one of which is also associated with CRAE. The 4 SNPs are rs7926971 in TEAD1 (p=3.1×10−11, minor allele frequency (MAF)=0.43), rs201259422 in TSPAN10 (p=4.4×10−9, MAF=0.27), rs5442 in GNB3 (p=7.0×10−10, MAF=0.05) and rs1800407 in OCA2 (p=3.4×10−8, MAF=0.05). The latter SNP, rs1800407, was also associated with CRAE (p=6.5×10−12). Results from the gene-based burden tests were null. In phenotype look-ups, SNP rs201255422 was associated with both systolic (p=0.001) and diastolic blood pressure (p=8.3×10−04). Conclusions Our study expands the understanding of genetic factors influencing the size of the retinal microvasculature. These findings may also provide insight into the relationship between retinal and systemic microvascular disease. PMID:26567291

  17. In vivo dynamics of retinal injury and repair in the rhodopsin mutant dog model of human retinitis pigmentosa.

    PubMed

    Cideciyan, Artur V; Jacobson, Samuel G; Aleman, Tomas S; Gu, Danian; Pearce-Kelling, Susan E; Sumaroka, Alexander; Acland, Gregory M; Aguirre, Gustavo D

    2005-04-05

    Genetic and environmental factors modify the severity of human neurodegenerations. Retinal degenerations caused by rhodopsin gene mutations show severity differences within and between families and even within regions of the same eye. Environmental light is thought to contribute to this variation. In the naturally occurring dog model of the human disorder, we found that modest light levels, as used in routine clinical practice, dramatically accelerated the neurodegeneration. Dynamics of acute retinal injury (consisting of abnormal intraretinal light scattering) were visualized in vivo in real time with high-resolution optical imaging. Long term consequences included fast or slow retinal degeneration or repair of injury depending on the dose of light exposure. These experiments provide a platform to study mechanisms of neuronal injury, repair, compensation, and degeneration. The data also argue for a gene-specific clinical trial of light reduction in human rhodopsin disease.

  18. In vivo dynamics of retinal injury and repair in the rhodopsin mutant dog model of human retinitis pigmentosa

    PubMed Central

    Cideciyan, Artur V.; Jacobson, Samuel G.; Aleman, Tomas S.; Gu, Danian; Pearce-Kelling, Susan E.; Sumaroka, Alexander; Acland, Gregory M.; Aguirre, Gustavo D.

    2005-01-01

    Genetic and environmental factors modify the severity of human neurodegenerations. Retinal degenerations caused by rhodopsin gene mutations show severity differences within and between families and even within regions of the same eye. Environmental light is thought to contribute to this variation. In the naturally occurring dog model of the human disorder, we found that modest light levels, as used in routine clinical practice, dramatically accelerated the neurodegeneration. Dynamics of acute retinal injury (consisting of abnormal intraretinal light scattering) were visualized in vivo in real time with high-resolution optical imaging. Long term consequences included fast or slow retinal degeneration or repair of injury depending on the dose of light exposure. These experiments provide a platform to study mechanisms of neuronal injury, repair, compensation, and degeneration. The data also argue for a gene-specific clinical trial of light reduction in human rhodopsin disease. PMID:15784735

  19. Intraocular retinal prosthesis.

    PubMed Central

    Humayun, M S

    2001-01-01

    PURPOSE: An electronic implant that can bypass the damaged photoreceptors and electrically stimulate the remaining retinal neurons to restore useful vision has been proposed. A number of key questions remain to make this approach feasible. The goal of this thesis is to address the following 2 specific null hypotheses: (1) Stimulus parameters make no difference in the electrically elicited retinal responses. (2) Just as we have millions of photoreceptors, so it will take a device that can generate millions of pixels/light points to create useful vision. METHODS: For electrophysiologic experiments, 2 different setups were used. In the first setup, charge-balanced pulses were delivered to the retinal surface via electrodes inserted through an open sky approach in normal or blind retinal degenerate (rd) mice. In the second setup, the rabbit retina was removed under red light conditions from an enucleated eye and then maintained in a chamber while being superfused with oxygenated, heated Ames media. In both setups, stimulating electrodes and recording electrodes were positioned on the retinal surface to evaluate the effect of varying stimulation parameters on the orthodromic retinal responses (i.e., recording electrode placed between stimulating electrodes and optic nerve head). For psychophysical experiments, visual images were divided into pixels of light that could be projected in a pattern on the retina in up to 8 sighted volunteers. Subjects were asked to perform various tasks ranging from reading and face recognition to various activities of daily living. RESULTS: Electrophysiologic experiments: In a normal mouse, a single cycle of a 1-kHz sine wave was significantly more efficient than a 1-kHz square wave (P < .05), but no such difference was noted in either of the 8- or 16-week-old rd mouse groups (8-week-old, P = .426; 16-week-old, P = .078). Charge threshold was significantly higher in 16-week-old rd mouse versus both 8-week-old rd and normal mouse for every

  20. Genomic Loci Modulating the Retinal Transcriptome in Wound Healing

    PubMed Central

    Vázquez-Chona, Félix R.; Lu, Lu; Williams, Robert W.; Geisert, Eldon E.

    2007-01-01

    Purpose The present study predicts and tests genetic networks that modulate gene expression during the retinal wound-healing response. Methods Upstream modulators and target genes were defined using meta-analysis and bioinformatic approaches. Quantitative trait loci (QTLs) for retinal acute phase genes (Vazquez-Chona et al. 2005) were defined using QTL analysis of CNS gene expression (Chesler et al. 2005). Candidate modulators were defined using computational analysis of gene and motif sequences. The effect of candidate genes on wound healing was tested using animal models of gene expression. Results A network of early wound-healing genes is modulated by a locus on chromosome 12. The genetic background of the locus altered the wound-healing response of the retina. The C57BL/6 allele conferred enhanced expression of neuronal marker Thy1 and heat-shock-like crystallins, whereas the DBA/2J allele correlated with greater levels of the classic marker of retinal stress, glial fibrillary acidic protein (GFAP). Id2 and Lpin1 are candidate upstream modulators as they strongly correlated with the segregation of DBA/2J and C57BL/6 alleles, and their dosage levels correlated with the enhanced expression of survival genes (Thy1 and crystallin genes). Conclusion We defined a genetic network associated with the retinal acute injury response. Using genetic linkage analysis of natural transcript variation, we identified regulatory loci and can didate modulators that control transcript levels of acute phase genes. Our results support the convergence of gene expression profiling, QTL analysis, and bioinformatics as a rational approach to discover molecular pathways controlling retinal wound healing. PMID:19936100

  1. Oral administration of a curcumin-phospholipid delivery system for the treatment of central serous chorioretinopathy: a 12-month follow-up study

    PubMed Central

    Mazzolani, Fabio; Togni, Stefano

    2013-01-01

    Background The therapeutic effects of Meriva®, a curcumin-phospholipid (lecithin) delivery system (formulated as Norflo® tablets), on visual acuity and retinal thickness in patients with acute and chronic central serous chorioretinopathy was previously investigated in a six-month open-label study. Methods In this follow-up study, visual acuity was again assessed by ophthalmologic evaluation and retinal thickness by optical coherence tomography (OCT). Norflo tablets were administered twice daily to patients with central serous chorioretinopathy. The study group consisted of 12 patients (total 18 eyes) who completed 12 months of follow-up. The primary endpoint was change in visual acuity before and after treatment with Norflo, and change in neuroretinal or retinal pigment epithelium detachment on OCT was the secondary endpoint. Results After 12 months of therapy, no eyes showed further reduction in visual acuity, 39% showed stabilization, and 61% showed statistically significant improvement (P = 0.0001 by Student’s t-test and P = 0.0005 by Wilcoxon signed rank test). Ninety-five percent of eyes showed a reduction in neuroretinal or retinal pigment epithelium detachment and 5% showed stabilization. The difference in retinal thickness after 12 months was statistically significant (P = 0.0001 by Student’s t-test and P = 0.0004 by Wilcoxon signed rank test). Conclusion These results, albeit preliminary, confirm our previous finding that this curcumin delivery system is effective in the management of central serous chorioretinopathy. When administered in a bioavailable formulation, curcumin is worth considering as a therapeutic agent for the management of inflammatory and degenerative eye conditions involving activation of retinal microglial cells. PMID:23723686

  2. High-speed adaptive optics line scan confocal retinal imaging for human eye

    PubMed Central

    Wang, Xiaolin; Zhang, Yuhua

    2017-01-01

    Purpose Continuous and rapid eye movement causes significant intraframe distortion in adaptive optics high resolution retinal imaging. To minimize this artifact, we developed a high speed adaptive optics line scan confocal retinal imaging system. Methods A high speed line camera was employed to acquire retinal image and custom adaptive optics was developed to compensate the wave aberration of the human eye’s optics. The spatial resolution and signal to noise ratio were assessed in model eye and in living human eye. The improvement of imaging fidelity was estimated by reduction of intra-frame distortion of retinal images acquired in the living human eyes with frame rates at 30 frames/second (FPS), 100 FPS, and 200 FPS. Results The device produced retinal image with cellular level resolution at 200 FPS with a digitization of 512×512 pixels/frame in the living human eye. Cone photoreceptors in the central fovea and rod photoreceptors near the fovea were resolved in three human subjects in normal chorioretinal health. Compared with retinal images acquired at 30 FPS, the intra-frame distortion in images taken at 200 FPS was reduced by 50.9% to 79.7%. Conclusions We demonstrated the feasibility of acquiring high resolution retinal images in the living human eye at a speed that minimizes retinal motion artifact. This device may facilitate research involving subjects with nystagmus or unsteady fixation due to central vision loss. PMID:28257458

  3. Serum lipid profiles and dyslipidaemia are associated with retinal microvascular changes in children and adolescents

    PubMed Central

    Xiao, Wei; Guo, Xinxing; Ding, Xiaohu; He, Mingguang

    2017-01-01

    The present study aims to assess the relationship between serum lipid parameters and retinal microvascular calibres in children and adolescents. A total of 950 participants aged 7 to 19 years were recruited. Central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) were measured from digital retinal images. Serological testing was performed to obtain lipid profiles. Dyslipidaemia was defined according to the US national expert panel guideline. After adjusted for age, sex, mean arterial blood pressure, axial length, body mass index and the fellow retinal vascular calibre, no significant association was found between retinal vascular diameters and any lipid parameters (all P > 0.05) in children younger than 12 years. Among the adolescents 12 years and older, increased triglycerides, total cholesterol, low-density lipoprotein cholesterol, and apoB were associated with decrease in CRAE (β = −1.33, −1.83, −1.92 and −7.18, P = 0.031, 0.003, 0.006, and 0.009, respectively). Compared with normolipidemic counterparts, adolescents with dyslipidaemia had significantly narrower retinal arteriolar diameters. No significant relationship between lipid subclass levels and CRVE was revealed in adolescents. The present findings suggest that the elevation of atherogenic lipids in adolescents is closely related to the adverse changes of retinal arterioles. Dyslipidaemia may affect systemic microvasculature from childhood on. PMID:28317946

  4. Notch signaling induces retinal stem-like properties in perinatal neural retina progenitors and promotes symmetric divisions in adult retinal stem cells.

    PubMed

    Balenci, Laurent; van der Kooy, Derek

    2014-02-01

    Understanding the mechanisms regulating retinal stem cell (RSC) activity is fundamental for future stem cell-based therapeutic purposes. By combining gain and loss of function approaches, we addressed whether Notch signaling may play a selective role in retinal stem versus retinal progenitor cells in both developing and adult eyes. Inhibition of either Notch or fibroblast growth factor signaling reduced proliferation of retinal stem and retinal progenitor cells, and inhibited RSC self-renewal. Conversely, exogenous Delta-like 3 and direct intrinsic Notch activation stimulated expansionary symmetric divisions in adult RSCs with the concomitant upregulation of Hes5. Knocking down Hes5 expression specifically decreased the numbers, but not the diameters, of adult RSC primary spheres, indicating that HES5 is the downstream effector of Notch receptor in controlling adult RSC proliferation. In addition, constitutive Notch activation induced retinal stem-like asymmetric self-renewal properties, with no expansion (no symmetrical division) in perinatal neural retina progenitor cells. These findings highlight central roles of Notch signaling activity in regulating the modes of division of retinal stem and retinal progenitor cells.

  5. Acute Toluene Exposure Alters Expression of Genes in the Central Nervous System Associated With Synaptic Structure and Function

    EPA Science Inventory

    Toluene is a volatile organic compound (VOC) and a ubiquitous air pollutant of interest to EPA regulatory programs. Whereas its acute functional effects are well described, several modes of action in the CNS have been proposed. Therefore, we sought to identify potential pathways ...

  6. Targeting Inflammation in Emerging Therapies for Genetic Retinal Disease

    PubMed Central

    Viringipurampeer, Ishaq A.; Bashar, Abu E.; Gregory-Evans, Cheryl Y.; Moritz, Orson L.; Gregory-Evans, Kevin

    2013-01-01

    Genetic retinal diseases such as age-related macular degeneration and monogenic diseases such as retinitis pigmentosa account for some of the commonest causes of blindness in the developed world. Diverse genetic abnormalities and environmental causes have been implicated in triggering multiple pathological mechanisms such as oxidative stress, lipofuscin deposits, neovascularisation, and programmed cell death. In recent years, inflammation has also been highlighted although whether inflammatory mediators play a central role in pathogenesis or a more minor secondary role has yet to be established. Despite this, numerous interventional studies, particularly targeting the complement system, are underway with the promise of novel therapeutic strategies for these important blinding conditions. PMID:23509666

  7. High resolution optoelectronic retinal prosthesis

    NASA Astrophysics Data System (ADS)

    Loudin, Jim; Dinyari, Rostam; Huie, Phil; Butterwick, Alex; Peumans, Peter; Palanker, Daniel

    2009-02-01

    Electronic retinal prostheses seek to restore sight in patients with retinal degeneration by delivering pulsed electric currents to retinal neurons via an array of microelectrodes. Most implants use inductive or optical transmission of information and power to an intraocular receiver, with decoded signals subsequently distributed to retinal electrodes through an intraocular cable. Surgical complexity could be minimized by an "integrated" prosthesis, in which both power and data are delivered directly to the stimulating array without any discrete components or cables. We present here an integrated retinal prosthesis system based on a photodiode array implant. Video frames are processed and imaged onto the retinal implant by a video goggle projection system operating at near-infrared wavelengths (~ 900 nm). Photodiodes convert light into pulsed electric current, with charge injection maximized by specially optimized series photodiode circuits. Prostheses of three different pixel densities (16 pix/mm2, 64 pix/mm2, and 256 pix/mm2) have been designed, simulated, and prototyped. Retinal tissue response to subretinal implants made of various materials has been investigated in RCS rats. The resulting prosthesis can provide sufficient charge injection for high resolution retinal stimulation without the need for implantation of any bulky discrete elements such as coils or tethers. In addition, since every pixel functions independently, pixel arrays may be placed separately in the subretinal space, providing visual stimulation to a larger field of view.

  8. Retinal Imaging and Image Analysis

    PubMed Central

    Abràmoff, Michael D.; Garvin, Mona K.; Sonka, Milan

    2011-01-01

    Many important eye diseases as well as systemic diseases manifest themselves in the retina. While a number of other anatomical structures contribute to the process of vision, this review focuses on retinal imaging and image analysis. Following a brief overview of the most prevalent causes of blindness in the industrialized world that includes age-related macular degeneration, diabetic retinopathy, and glaucoma, the review is devoted to retinal imaging and image analysis methods and their clinical implications. Methods for 2-D fundus imaging and techniques for 3-D optical coherence tomography (OCT) imaging are reviewed. Special attention is given to quantitative techniques for analysis of fundus photographs with a focus on clinically relevant assessment of retinal vasculature, identification of retinal lesions, assessment of optic nerve head (ONH) shape, building retinal atlases, and to automated methods for population screening for retinal diseases. A separate section is devoted to 3-D analysis of OCT images, describing methods for segmentation and analysis of retinal layers, retinal vasculature, and 2-D/3-D detection of symptomatic exudate-associated derangements, as well as to OCT-based analysis of ONH morphology and shape. Throughout the paper, aspects of image acquisition, image analysis, and clinical relevance are treated together considering their mutually interlinked relationships. PMID:21743764

  9. Will Retinal Implants Restore Vision?

    NASA Astrophysics Data System (ADS)

    Zrenner, Eberhart

    2002-02-01

    A number of research groups are developing electrical implants that can be attached directly to the retina in an attempt to restore vision to patients suffering from retinal degeneration. However, despite promising results in animal experiments, there are still several major obstacles to overcome before retinal prostheses can be used clinically.

  10. Low Level Laser Retinal Damage

    DTIC Science & Technology

    1990-03-01

    18 Related Projects ........................ . . ....... 20 References . . . . .......................... 22 2 INTRODUCTION The objectives of...fluorescein is a potent phototoxic agent in the retina.26 The damage threshold for blue light retinal damage is lowered by a factor of ten after an... Related to the Probiem of Retinal Light Damage 1. Corneal Holography 2. Hematoporphyrin Studies 3. Fluorescein Fluorescence Measurements 7 EQUIPMENT

  11. Perceptual Fading without Retinal Adaptation

    ERIC Educational Resources Information Center

    Hsieh, Po-Jang; Colas, Jaron T.

    2012-01-01

    A retinally stabilized object readily undergoes perceptual fading and disappears from consciousness. This startling phenomenon is commonly believed to arise from local bottom-up sensory adaptation to edge information that occurs early in the visual pathway, such as in the lateral geniculate nucleus of the thalamus or retinal ganglion cells. Here…

  12. [Multicenter evaluation of h-FABP semi-quantitative assay (Cardio Detect) in central laboratory: the point in acute myocardial infarction diagnosis].

    PubMed

    Lefèvre, G; Fayet, J-M; Graïne, H; Berny, C; Maupas-Schwalm, F; Capolaghi, B; Morin, C

    2007-01-01

    The diagnostic performance of heart-Fatty Acid Binding Protein (h-FABP) (semi-quantitative CardioDetect test) and cardiac troponin I (TnIc) blood assays were compared in one hundred patients presenting with suspicion of acute coronary syndrome. Final patient diagnosis was "acute myocardial infarction" in 36 cases, "non ST myocardial infarction" in 25 cases and "non ischemic pathologies" in 39 cases. h-FABP results were positive in 26 patients, negative in 57 patients and ambiguous in 17 patients, the latter corresponding to the final diagnosis of "acute myocardial infarction" in 5 cases, "non ST myocardial infarction" in 2 cases and "non ischemic pathologies " in 10 cases. At admission, h-FABP and TnIc exhibiteda sensitivity of 54% an 66%, respectively and a specificity of 86% and 95%, respectively. Positive and negative predictive values were 81% and 64% for h-FABP, respectively and 92% and 75% for cTnI, respectively. h-FABP and cTnI demonstrated a similar diagnostic efficiency if admission delay is less than 4 hours after onset of chest pain (area under ROC curve TnIc = 0.767 +/- 0.091 ; area under ROC curve h-FABP = 0.622 +/- 0.109 ; p = 0.144). On the contrary, cTnI assay demonstrated a better efficiency than h-FABP (p< 0.005) for patients admitted in a delay of 4 to 12 hours after the onset of chest pain. If chosen cTnI cut-off corresponded to the recent consensus definition used for monitoring acute coronary syndrome patients, h-FABP semi-quantitative assay realized within central laboratory did not demonstrated a better diagnostic efficiency than cTnI.

  13. MMP-3 Deficiency Alleviates Endotoxin-Induced Acute Inflammation in the Posterior Eye Segment

    PubMed Central

    Van Hove, Inge; Lefevere, Evy; De Groef, Lies; Sergeys, Jurgen; Salinas-Navarro, Manuel; Libert, Claude; Vandenbroucke, Roosmarijn; Moons, Lieve

    2016-01-01

    Matrix metalloproteinase-3 (MMP-3) is known to mediate neuroinflammatory processes by activating microglia, disrupting blood–central nervous system barriers and supporting neutrophil influx into the brain. In addition, the posterior part of the eye, more specifically the retina, the retinal pigment epithelium (RPE) and the blood–retinal barrier, is affected upon neuroinflammation, but a role for MMP-3 during ocular inflammation remains elusive. We investigated whether MMP-3 contributes to acute inflammation in the eye using the endotoxin-induced uveitis (EIU) model. Systemic administration of lipopolysaccharide induced an increase in MMP-3 mRNA and protein expression level in the posterior part of the eye. MMP-3 deficiency or knockdown suppressed retinal leukocyte adhesion and leukocyte infiltration into the vitreous cavity in mice subjected to EIU. Moreover, retinal and RPE mRNA levels of intercellular adhesion molecule 1 (Icam1), interleukin 6 (Il6), cytokine-inducible nitrogen oxide synthase (Nos2) and tumor necrosis factor α (Tnfα), which are key molecules involved in EIU, were clearly reduced in MMP-3 deficient mice. In addition, loss of MMP-3 repressed the upregulation of the chemokines monocyte chemoattractant protein (MCP)-1 and (C-X-C motif) ligand 1 (CXCL1). These findings suggest a contribution of MMP-3 during EIU, and its potential use as a therapeutic drug target in reducing ocular inflammation. PMID:27809288

  14. Amyloidosis in Retinal Neurodegenerative Diseases

    PubMed Central

    Masuzzo, Ambra; Dinet, Virginie; Cavanagh, Chelsea; Mascarelli, Frederic; Krantic, Slavica

    2016-01-01

    As a part of the central nervous system, the retina may reflect both physiological processes and abnormalities related to pathologies that affect the brain. Amyloidosis due to the accumulation of amyloid-beta (Aβ) was initially regarded as a specific and exclusive characteristic of neurodegenerative alterations seen in the brain of Alzheimer’s disease (AD) patients. More recently, it was discovered that amyloidosis-related alterations, similar to those seen in the brain of Alzheimer’s patients, also occur in the retina. Remarkably, these alterations were identified not only in primary retinal pathologies, such as age-related macular degeneration (AMD) and glaucoma, but also in the retinas of Alzheimer’s patients. In this review, we first briefly discuss the biogenesis of Aβ, a peptide involved in amyloidosis. We then discuss some pathological aspects (synaptic dysfunction, mitochondrial failure, glial activation, and vascular abnormalities) related to the neurotoxic effects of Aβ. We finally highlight common features shared by AD, AMD, and glaucoma in the context of Aβ amyloidosis and further discuss why the retina, due to the transparency of the eye, can be considered as a “window” to the brain. PMID:27551275

  15. Interactions of norepinephrine and galanin in the central amygdala and lateral bed nucleus of the stria terminalis modulate the behavioral response to acute stress.

    PubMed

    Morilak, David A; Cecchi, Marco; Khoshbouei, Habibeh

    2003-06-27

    Many aspects of drug abuse and addiction share neurobiological substrates with the modulatory processes underlying the response and adaptation to acute stress. In particular, the ascending noradrenergic system has been implicated in facilitating the response to stress, and in stress-induced reinstatement of drug seeking behavior. Thus, to better understand the link between stress and addictive behaviors, it would be informative to understand better the modulatory function of the ascending noradrenergic system, and its interaction with other neurotransmitters with which it is closely associated or co-localized, such as the neuropeptide galanin. In this paper, we review a series of studies investigating the functional interactions of norepinephrine and galanin in modulating the behavioral response to acute stress in two components of the extended amygdala, the central nucleus of the amygdala and the lateral bed nucleus of the stria terminalis. We showed that norepinephrine facilitates behavioral reactivity to stress on the elevated plus-maze and social interaction tests. However, when stress-induced activation of the noradrenergic system was enhanced by blocking inhibitory adrenergic autoreceptors, galanin release was recruited in the central amygdala, acting to attenuate the behavioral response to stress. By contrast, stress-induced galanin release in the lateral bed nucleus appeared to be independent of enhanced noradrenergic activation, and unlike the central amygdala, both galanin and norepinephrine facilitated behavioral stress reactivity in the bed nucleus. The different modes of interaction and differential region- and response-specificity of galanin and norepinephrine suggest that a complex neural circuit interconnecting these two regions is involved in the modulatory effects of norepinephrine and galanin on the behavioral response to stress. Such complexity may allow for flexibility and plasticity in stress adaptation, and may also contribute to behavioral

  16. Hyperoxia-Induced Proliferative Retinopathy: Early Interruption of Retinal Vascular Development with Severe and Irreversible Neurovascular Disruption

    PubMed Central

    Lajko, Michelle; Cardona, Herminio J.; Taylor, Joann M.; Shah, Ronil S.; Farrow, Kathryn N.; Fawzi, Amani A.

    2016-01-01

    Bronchopulmonary dysplasia (BPD) is a major cause of neonatal morbidity in premature infants, occurring as a result of arrested lung development combined with multiple postnatal insults. Infants with BPD exposed to supplemental oxygen are at risk of retinopathy of prematurity as well. Thus, we studied the effects of hyperoxia on the retinal vasculature in a murine model of BPD. The retinal phenotype of this model, which we termed hyperoxia-induced proliferative retinopathy (HIPR), shows severe disruption of retinal vasculature and loss of vascular patterning, disorganized intra-retinal angiogenesis, inflammation and retinal detachment. Neonatal mice were subjected to 75% oxygen exposure from postnatal day (P)0 to P14 to model BPD, then allowed to recover in room air for 1 (P15), 7 (P21), or 14 days (P28). We quantified retinal thickness, protein levels of HIF-1α, NOX2, and VEGF, and examined the cellular locations of these proteins by immunohistochemistry. We examined the retinal blood vessel integrity and inflammatory markers, including macrophages (F4/80) and lymphocytes (CD45R). Compared to controls, normal retinal vascular development was severely disrupted and replaced by a disorganized sheet of intra-retinal angiogenesis in the HIPR mice. At all time-points, HIPR showed persistent hyaloidal vasculature and a significantly thinner central retina compared to controls. HIF-1α protein levels were increased at P15, while VEGF levels continued to increase until P21. Intra-retinal fibrinogen was observed at P21 followed by sub-retinal deposition in at P28. Inflammatory lymphocytes and macrophages were observed at P21 and P28, respectively. This model presents a severe phenotype of disrupted retinal vascular development, intra-retinal angiogenesis inflammation and retinal detachment. PMID:27861592

  17. A morphological study of the retinal ganglion cells of the Afghan pika (Ochotona rufescens).

    PubMed

    Akaishi, Y; Uchiyama, H; Ito, H; Shimizu, Y

    1995-03-01

    The distribution and morphology of the retinal ganglion cells was studied in a relative of the rabbit, the Afghan pika. The total number of retinal ganglion cells was approximately 170,000. The total number of optic nerve fibers was between 160,000 and 190,000, corresponding to the total number of retinal ganglion cells. Retinal ganglion cells were found to have a horizontal region of high-density. The maximum density was 5250 cells/mm2. This region was located in the central retina below the optic disc. This area contained numerous closely packed small ganglion cells, while the peripheral retina (especially in the dorsal periphery) contained large ganglion cells more loosely dispersed. The retinal ganglion cells labeled by horseradish peroxidase (HRP) were morphologically classified into three types based on dendritic length and ramification pattern.

  18. Retinal Remodeling and Metabolic Alterations in Human AMD.

    PubMed

    Jones, Bryan W; Pfeiffer, Rebecca L; Ferrell, William D; Watt, Carl B; Tucker, James; Marc, Robert E

    2016-01-01

    Age-related macular degeneration (AMD) is a progressive retinal degeneration resulting in central visual field loss, ultimately causing debilitating blindness. AMD affects 18% of Americans from 65 to 74, 30% older than 74 years of age and is the leading cause of severe vision loss and blindness in Western populations. While many genetic and environmental risk factors are known for AMD, we currently know less about the mechanisms mediating disease progression. The pathways and mechanisms through which genetic and non-genetic risk factors modulate development of AMD pathogenesis remain largely unexplored. Moreover, current treatment for AMD is palliative and limited to wet/exudative forms. Retina is a complex, heterocellular tissue and most retinal cell classes are impacted or altered in AMD. Defining disease and stage-specific cytoarchitectural and metabolic responses in AMD is critical for highlighting targets for intervention. The goal of this article is to illustrate cell types impacted in AMD and demonstrate the implications of those changes, likely beginning in the retinal pigment epithelium (RPE), for remodeling of the the neural retina. Tracking heterocellular responses in disease progression is best achieved with computational molecular phenotyping (CMP), a tool that enables acquisition of a small molecule fingerprint for every cell in the retina. CMP uncovered critical cellular and molecular pathologies (remodeling and reprogramming) in progressive retinal degenerations such as retinitis pigmentosa (RP). We now applied these approaches to normal human and AMD tissues mapping progression of cellular and molecular changes in AMD retinas, including late-stage forms of the disease.

  19. Small molecules targeting glycogen synthase kinase 3 as potential drug candidates for the treatment of retinitis pigmentosa.

    PubMed

    Marchena, Miguel; Villarejo-Zori, Beatriz; Zaldivar-Diez, Josefa; Palomo, Valle; Gil, Carmen; Hernández-Sánchez, Catalina; Martínez, Ana; de la Rosa, Enrique J

    2017-12-01

    Retinitis pigmentosa (RP) is an inherited retinal dystrophy that courses with progressive degeneration of retinal tissue and loss of vision. Currently, RP is an unpreventable, incurable condition. We propose glycogen synthase kinase 3 (GSK-3) inhibitors as potential leads for retinal cell neuroprotection, since the retina is also a part of the central nervous system and GSK-3 inhibitors are potent neuroprotectant agents. Using a chemical genetic approach, diverse small molecules with different potency and binding mode to GSK-3 have been used to validate and confirm GSK-3 as a pharmacological target for RP. Moreover, this medicinal chemistry approach has provided new leads for the future disease-modifying treatment of RP.

  20. Acute inhibition of central c-Jun N-terminal kinase restores hypothalamic insulin signalling and alleviates glucose intolerance in diabetic mice.

    PubMed

    Benzler, J; Ganjam, G K; Legler, K; Stöhr, S; Krüger, M; Steger, J; Tups, A

    2013-05-01

    The hypothalamus has been identified as a main insulin target tissue for regulating normal body weight and glucose metabolism. Recent observations suggest that c-Jun-N-terminal kinase (JNK)-signalling plays a crucial role in the development of obesity and insulin resistance because neuronal JNK-1 ablation in the mouse prevented high-fat diet-induced obesity (DIO) and increased energy expenditure, as well as insulin sensitivity. In the present study, we investigated whether central JNK inhibition is associated with sensitisation of hypothalamic insulin signalling in mice fed a high-fat diet for 3 weeks and in leptin-deficient mice. We determined whether i.c.v. injection of a pharmacological JNK-inhibitor (SP600125) improved impaired glucose homeostasis. By immunohistochemistry, we first observed that JNK activity was increased in the arcuate nucleus (ARC) and the ventromedial hypothalamus (VMH) in both mouse models, relative to normoglycaemic controls. This suggests that up-regulation of JNK in these regions is associated with glucose intolerance and obesity, independent of leptin levels. Acute i.c.v. injection of SP600125 ameliorated glucose tolerance within 30 min in both leptin-deficient and DIO mice. Given the acute nature of i.c.v. injections, these effects cannot be attributed to changes in food intake or energy balance. In a hypothalamic cell line, and in the ARC and VMH of leptin-deficient mice, JNK inhibition by SP600125 consistently improved impaired insulin signalling. This was determined by a reduction of phospho-insulin receptor substrate-1 [IRS-1(Ser612)] protein in a hypothalamic cell line and a decline in the number of pIRS-1(Ser612) immunoreactive cells in the ARC and VMH. Serine 612 phosphorylation of IRS-1 is assumed to negatively regulate insulin signalling. In leptin-deficient mice, in both nuclei, central inhibition of JNK increased the number of cells immunoreactive for phospho-Akt (Ser473) and phospho-GSK-3β (Ser9), which are important

  1. Electroretinographic assessment of retinal function at high altitude.

    PubMed

    Schatz, Andreas; Willmann, Gabriel; Fischer, M Dominik; Schommer, Kai; Messias, André; Zrenner, Eberhart; Bartz-Schmidt, Karl-Ulrich; Gekeler, Florian

    2013-08-01

    Although hypoxia plays a key role in the pathophysiology of many common and well studied retinal diseases, little is known about the effects of high-altitude hypoxia on retinal function. The aim of the present study was to assess retinal function during exposure to high-altitude hypoxia using electroretinography (ERG). This work is related to the Tübingen High Altitude Ophthalmology (THAO) study. Electroretinography was performed in 14 subjects in Tübingen, Germany (341 m) and at high altitude at La Capanna Regina Margherita, Italy (4,559 m) using an extended protocol to assess functional integrity of various retinal layers. To place findings in the context of acute mountain sickness, correlations between ERG measurements and oxygen saturation, heart rate, and scores of acute mountain sickness (AMS) were calculated. At high altitude, the maximum response of the scotopic sensitivity function, the implicit times of the a- and b-wave of the combined rod-cone responses, and the implicit times of the photopic negative responses (PhNR) were significantly altered. A-wave slopes and i-waves were significantly decreased at high altitude. The strongest correlation was found for PhNR and O2 saturation (r = 0.68; P < 0.05). Of all tested correlations, only the photopic b-wave implicit time (10 cd·s/m(2)) was significantly correlated with severity of AMS (r = 0.57; P < 0.05). ERG data show that retinal function of inner, outer, and ganglion cell layer is altered at high-altitude hypoxia. Interestingly, the most affected ERG parameters are related to combined rod-cone responses, which indicate that phototransduction and visual processing, especially under conditions of rod-cone interaction, are primarily affected at high altitude.

  2. Selective retinal therapy with a continuous line scanning laser

    NASA Astrophysics Data System (ADS)

    Paulus, Yannis M.; Jain, ATul; Gariano, Ray F.; Nomoto, Hiroyuki; Schuele, Georg; Sramek, Christopher; Charalel, Resmi; Palanker, Daniel

    2010-02-01

    This study evaluates the effects of exposure duration, beam diameter, and power on the safety, selectivity, and healing of retinal lesions created using a continuous line scanning laser. A 532 nm laser (PASCALTM) with retinal beam diameters of 40 and 66 μm was applied to 60 eyes of 30 Dutch-Belted rabbits. Retinal exposure duration varied from 15 to 60 μs. Lesions were acutely assessed by ophthalmoscopy and fluorescein angiography (FA). RPE flatmounts were evaluated with live-dead fluorescent assay (LD). Histological analysis was performed at 1 hour, 1 and 3 days, 1 and 2 weeks, and 1 and 2 months following laser treatment. Ophthalmoscopic visibility (OV) of the lesions corresponded to photoreceptor damage on histological analysis at 1 hour. In subvisible lesions, FA and LD yielded similar thresholds of RPE damage. The ratios of the threshold of rupture and of OV to FA visibility (measures of safety and selectivity) increased with decreasing duration and beam diameter. Above the threshold of OV, histology showed focal RPE damage and photoreceptor loss at one day without inner retinal effects. By one week, continuity of photoreceptor and RPE layers was restored. By 1 month, photoreceptors appeared normal while hypertrophy and hyperpigmentation of the RPE persisted. Retinal therapy with a fast scanning continuous laser achieves selective targeting of the RPE and, at higher power, of the photoreceptors. The damage zone in the photoreceptor layer is quickly filled-in, likely due to photoreceptor migration from adjacent zones. Continuous scanning laser can treat large retinal areas within standard eye fixation time.

  3. Severity of middle cerebral artery occlusion determines retinal deficits in rats

    PubMed Central

    Allen, Rachael S.; Sayeed, Iqbal; Cale, Heather A.; Morrison, Katherine C.; Boatright, Jeffrey H.; Pardue, Machelle T.; Stein, Donald G.

    2014-01-01

    Middle cerebral artery occlusion (MCAO) using the intraluminal suture technique is a common model used to study cerebral ischemia in rodents. Due to the proximity of the ophthalmic artery to the middle cerebral artery, MCAO blocks both arteries, causing both cerebral and retinal ischemia. While previous studies have shown retinal dysfunction at 48 hours post-MCAO, we investigated whether these retinal function deficits persist until 9 days and whether they correlate with central neurological deficits. Rats received 90 minutes of transient MCAO followed by electroretinography at 2 and 9 days to assess retinal function. Retinal damage was assessed with cresyl violet staining, immunohistochemistry for glial fibrillary acidic protein (GFAP) and glutamine synthetase, and TUNEL staining. Rats showed behavioral deficits as assessed with neuroscore that correlated with cerebral infarct size and retinal function at 2 days. Two days after surgery, rats with moderate MCAO (neuroscore < 5) exhibited delays in electroretinogram implicit time, while rats with severe MCAO (neuroscore ≥ 5) exhibited reductions in amplitude. Glutamine synthetase was upregulated in Müller cells 3 days after MCAO in both severe and moderate animals, however, retinal ganglion cell death was only observed in MCAO retinas from severe animals. By 9 days after MCAO, both glutamine synthetase labeling and electroretinograms had returned to normal levels in moderate animals. Early retinal function deficits correlated with behavioral deficits. However, retinal function decreases were transient and selective retinal cell loss was observed only with severe ischemia, suggesting that the retina is less susceptible to MCAO than the brain. Temporary retinal deficits caused by MCAO are likely due to ischemia-induced increases in extracellular glutamate that impair signal conduction, but resolve by 9 days after MCAO. PMID:24518488

  4. The Relationship Between Intrinsic and Extrinsic Factors and Central Venous Catheter Infections in the Acutely Ill Patient

    DTIC Science & Technology

    1991-01-01

    patient. Extrinsic factors include central venous catheter insertion variables such as type of catheter, experience of person who inserted catheter...contact, common-vehicle, airborne and vectorborne. Diseases or infections that are spread by contact require exposure to the source either directly ( person ...to- person ), indirectly (microorganism is passed to an intermediate object) or droplet spread (passage of infectious agent through air). Illnesses

  5. Late Postoperative Evaluation of Retinal and Choroidal Thickness and Retinal Vessel Caliber after Surgical Repair of Corneal Perforation

    PubMed Central

    Pekel, Gökhan; Acer, Semra; Cesur, Nihal; Yağcı, Ramazan; Nevin Çetin, Ebru

    2015-01-01

    Objectives: To examine the late period retinal and choroidal alterations in the posterior pole of eyes that underwent primary suturing due to traumatic corneal perforation. Materials and Methods: This cross-sectional case series included 21 eyes of 21 patients. The fellow eyes served as the control group. Macular thickness, peripapillary retinal nerve fiber layer (RNFL) thickness, choroidal thickness, and retinal vessel caliber measurements were performed by spectral-domain optical coherence tomography (SD-OCT). Results: The mean RNFL thickness was 102.1±10.9 µm in the perforated eyes and 99.5±8.5 µm in the fellow eyes (p=0.29). The mean central macular thickness was 300.1±25.6 µm in the perforated eyes and 295.6±23.2 µm in the fellow eyes (p=0.62). The choroidal thickness and retinal vascular caliber measurements were also similar between the groups (p>0.05). Conclusion: Operated traumatic corneal perforations do not cause significant posterior pole retinal and choroidal SD-OCT thickness changes in the late postoperative period. PMID:27800241

  6. PIMASERTIB AND SEROUS RETINAL DETACHMENTS

    PubMed Central

    AlAli, Alaa; Bushehri, Ahmad; Park, Jonathan C.; Krema, Hatem

    2016-01-01

    Purpose: To report a case of multifocal serous retinal detachments associated with pimasertib. Methods: The authors report a 26-year-old patient who developed bilateral multifocal serous retinal detachments appearing 2 days after starting pimasertib (as part of a clinical trial investigating its use in low-grade metastatic ovarian cancer) and rapidly resolving 3 days after stopping it. Conclusion: The mechanism of MEK inhibitor induced visual toxicity remains unclear. The pathophysiology of multifocal serous retinal detachments as a complication of pimasertib is still poorly understood. PMID:26444523

  7. Retinal pseudoangiitis after intravitreal triamcinolone

    PubMed Central

    García-Campos, Jose Manuel; García-Basterra, Ignacio; Kamal-Salah, Radua; Baquero-Aranda, Isabel

    2015-01-01

    We present a case of a 40-year-old woman with a fundus image similar to frosted retinal angiitis after undergoing pars plana vitrectomy and intravitreal triamcinolone injection. The patient with diabetic retinopathy was referred to our hospital with vision loss in her right eye secondary to vitreous haemorrhage. After pars plana vitrectomy and injection of triamcinolone acetonide a funduscopy examination revealed deposits of triamcinolone along the retinal vessels simulating a frosted retinal angiitis. Triamcinolone deposits along blood vessels could be the result of the reabsorption process of these crystals by the perivascular macrophages. Further studies are needed. PMID:25678611

  8. Misfolded Proteins and Retinal Dystrophies

    PubMed Central

    Lin, Jonathan H.; LaVail, Matthew M.

    2010-01-01

    Many mutations associated with retinal degeneration lead to the production of misfolded proteins by cells of the retina. Emerging evidence suggests that these abnormal proteins cause cell death by activating the Unfolded Protein Response, a set of conserved intracellular signaling pathways that detect protein misfolding within the endoplasmic reticulum and control protective and proapoptotic signal transduction pathways. Here, we review the misfolded proteins associated with select types of retinitis pigmentosa, Stargadt-like macular degeneration, and Doyne Honeycomb Retinal Dystrophy and discuss the role that endoplasmic reticulum stress and UPR signaling play in their pathogenesis. Last, we review new therapies for these diseases based on preventing protein misfolding in the retina. PMID:20238009

  9. Adenosine triphosphate-induced photoreceptor death and retinal remodeling in rats.

    PubMed

    Vessey, Kirstan A; Greferath, Ursula; Aplin, Felix P; Jobling, Andrew I; Phipps, Joanna A; Ho, Tracy; De Iongh, Robbert U; Fletcher, Erica L

    2014-09-01

    Many common causes of blindness involve the death of retinal photoreceptors, followed by progressive inner retinal cell remodeling. For an inducible model of retinal degeneration to be useful, it must recapitulate these changes. Intravitreal administration of adenosine triphosphate (ATP) has recently been found to induce acute photoreceptor death. The aim of this study was to characterize the chronic effects of ATP on retinal integrity. Five-week-old, dark agouti rats were administered 50 mM ATP into the vitreous of one eye and saline into the other. Vision was assessed using the electroretinogram and optokinetic response and retinal morphology investigated via histology. ATP caused significant loss of visual function within 1 day and loss of 50% of the photoreceptors within 1 week. At 3 months, 80% of photoreceptor nuclei were lost, and total photoreceptor loss occurred by 6 months. The degeneration and remodeling were similar to those found in heritable retinal dystrophies and age-related macular degeneration and included inner retinal neuronal loss, migration, and formation of new synapses; Müller cell gliosis, migration, and scarring; blood vessel loss; and retinal pigment epithelium migration. In addition, extreme degeneration and remodeling events, such as neuronal and glial migration outside the neural retina and proliferative changes in glial cells, were observed. These extreme changes were also observed in the 2-year-old P23H rhodopsin transgenic rat model of retinitis pigmentosa. This ATP-induced model of retinal degeneration may provide a valuable tool for developing pharmaceutical therapies or for testing electronic implants aimed at restoring vision.

  10. Adenosine triphosphate-induced photoreceptor death and retinal remodeling in rats

    PubMed Central

    Vessey, Kirstan A; Greferath, Ursula; Aplin, Felix P; Jobling, Andrew I; Phipps, Joanna A; Ho, Tracy; De Iongh, Robbert U; Fletcher, Erica L

    2014-01-01

    Many common causes of blindness involve the death of retinal photoreceptors, followed by progressive inner retinal cell remodeling. For an inducible model of retinal degeneration to be useful, it must recapitulate these changes. Intravitreal administration of adenosine triphosphate (ATP) has recently been found to induce acute photoreceptor death. The aim of this study was to characterize the chronic effects of ATP on retinal integrity. Five-week-old, dark agouti rats were administered 50 mM ATP into the vitreous of one eye and saline into the other. Vision was assessed using the electroretinogram and optokinetic response and retinal morphology investigated via histology. ATP caused significant loss of visual function within 1 day and loss of 50% of the photoreceptors within 1 week. At 3 months, 80% of photoreceptor nuclei were lost, and total photoreceptor loss occurred by 6 months. The degeneration and remodeling were similar to those found in heritable retinal dystrophies and age-related macular degeneration and included inner retinal neuronal loss, migration, and formation of new synapses; Müller cell gliosis, migration, and scarring; blood vessel loss; and retinal pigment epithelium migration. In addition, extreme degeneration and remodeling events, such as neuronal and glial migration outside the neural retina and proliferative changes in glial cells, were observed. These extreme changes were also observed in the 2-year-old P23H rhodopsin transgenic rat model of retinitis pigmentosa. This ATP-induced model of retinal degeneration may provide a valuable tool for developing pharmaceutical therapies or for testing electronic implants aimed at restoring vision. J. Comp. Neurol. 522:2928–2950, 2014. © 2014 Wiley Periodicals, Inc. PMID:24639102

  11. [Aging and retinal vascular diseases].

    PubMed

    Takagi, Hitoshi

    2007-03-01

    Ocular vascular diseases such as diabetic retinopathy, retinal vein occlusion, and age-related macular degeneration, whose population increases along with aging, have become leading causes of severe visual disturbance. Macular edema and serous retinal detachment are associated with abnormal vascular leakage and tractional retinal detachment, and neovascular glaucoma is caused by retinal neovascularization. Such ocular vascular diseases are caused by vascular cell aging and vascular damage associated with lifestyle-related diseases including diabetes mellitus, hypertension, hyperlipidemia, and obesity. In the present study, we investigated molecular mechanisms in such vascular deficiencies using vascular cell biology methodology, and we propose novel strategies for the treatment of such vascular diseases. Along with aging, oxidative stress and physical stress, such as mechanical stretch, continuously and directly insult vascular cells. Such stress induces apoptosis by intracellular signaling through stress kinases in cultured retinal vascular cells. Inhibition of such stress kinases could be an effective treatment to protect the vascular cells against age-related damage. In a retinal vascular developmental model, pericyte loss causes pathology mimicking macular edema and proliferative diabetic retinopathy. Angiopoietin 1 (Ang 1) secreted by pericytes suppresses oxidative stress-induced intracellular signaling through stress kinases linked to cell apoptosis and normalizes such retinal pathology. This suggests that the paracrine action of Ang 1 in the pericytes is necessary to sustain normal retinal vasculature, and that Ang 1-triggered intracellular signaling is useful for the treatment of vascular cell pathology associated with pericyte loss. In diabetic retinopathy and retinal vein occlusion, retinal vessels regress along with retinal vascular cell apoptosis, and the retina becomes ischemic followed by pathological retinal neovascularization. VEGF has been

  12. Effects of 5-HT-receptor and alpha 2-adrenoceptor ligands on the haemodynamic response to acute central hypovolaemia in conscious rabbits.

    PubMed Central

    Evans, R. G.; Haynes, J. M.; Ludbrook, J.

    1993-01-01

    1. We set out to elucidate the pharmacological mechanisms by which alpha 2-adrenoceptor and 5-HT-receptor ligands affect the haemodynamic response to acute central hypovolaemia in conscious rabbits. 2. Acute central hypovolaemia was produced by inflating an inferior vena caval cuff so that cardiac output fell at a constant rate of approximately 8.5% of its baseline level per min. 3. Drugs were administered into the fourth cerebral ventricle in either 154 mM NaCl (saline) or 20% w/v 2-hydroxypropyl-beta-cyclodextrin (beta-CDX). After vehicle treatments, the haemodynamic response to acute central hypovolaemia had the usual two phases. During Phase I, systemic vascular conductance fell in proportion to cardiac output so that mean arterial pressure fell by only 8 mmHg. Phase II commenced when cardiac output had fallen to approximately 60% of its baseline level, when vascular conductance rose abruptly and arterial pressure fell to < or = 40 mmHg. The haemodynamic response was not dependent on the vehicle used (saline or beta-CDX). 4. Methysergide delayed the occurrence of Phase II in a dose-dependent manner, and prevented it at a dose of 30- 600 nmol (geometric mean = 186 nmol). The effects and potency of methysergide were not dependent on the vehicle used, indicating that beta-CDX can be used as a vehicle for fourth ventricular administration of lipophilic drugs to conscious rabbits. Clonidine (10 nmol) reversed the effects of a critical dose of methysergide. 5. Phase II was also prevented by 8-hydroxy-2-(di-n-propylamino)tetralin (5-HT1A-selective agonist, geometric mean critical dose (range) = 13.1 (10-30) nmol), sumatriptan (5-HT1D-selective agonist, 72.1 (10-300) nmol), mesulergine (5-HT2/1C-selective antagonist, 173 (30-1000) nmol), idazoxan (alpha 2-adrenoceptor-selective antagonist, 548 (100-3000) nmol), and mianserin (5-HT2/1C-selective antagonist, 548 (100-3000) nmol). It was not affected by MDL 72222 (5-HT3-selective antagonist, 300 nmol) or ketanserin (5-HT2

  13. Acute central administration of immepip, a histamine H3 receptor agonist, suppresses hypothalamic histamine release and elicits feeding behavior in rats.

    PubMed

    Chiba, Seiichi; Itateyama, Emi; Sakata, Toshiie; Yoshimatsu, Hironobu

    2009-04-06

    Histamine suppresses feeding behavior via histamine H1 receptors in the hypothalamus. This study was performed to examine whether the acute reduction of histamine release in the hypothalamus caused by immepip, a histamine H3 agonist, modulates the feeding behavior of rats. Rats had a catheter implanted in the third cerebral ventricle (i3v) and were given central injections of phosphate-buffered-saline or immepip (100-300 pmol/rat). Following the i3v administration of immepip, the rats developed dose-dependent hypokinesia within 10 min of administration. Next to hypokinesia, the rats showed significant dose-dependent feeding behavior. High-performance liquid chromatography (HPLC) confirmed the reduction in histamine release in the hypothalamus of rats following i3v administration of immepip. These results suggest that i3v administration of immepip, an H3 receptor agonist, suppresses hypothalamic histamine release and elicits feeding behavior in rats.

  14. Central Agonism of GPR120 Acutely Inhibits Food Intake and Food Reward and Chronically Suppresses Anxiety-Like Behavior in Mice

    PubMed Central

    Fisette, Alexandre; Fernandes, Maria F.; Hryhorczuk, Cécile; Poitout, Vincent; Alquier, Thierry; Fulton, Stephanie

    2016-01-01

    Background: GPR120 (FFAR4) is a G-protein coupled receptor implicated in the development of obesity and the antiinflammatory and insulin-sensitizing effects of omega-3 (ω-3) polyunsaturated fatty acids. Increasing central ω-3 polyunsaturated fatty acid levels has been shown to have both anorectic and anxiolytic actions. Despite the strong clinical interest in GPR120, its role in the brain is largely unknown, and thus we sought to determine the impact of central GPR120 pharmacological activation on energy balance, food reward, and anxiety-like behavior. Methods: Male C57Bl/6 mice with intracerebroventricular cannulae received a single injection (0.1 or 1 µM) or continuous 2-week infusion (1 µM/d; mini-pump) of a GPR120 agonist or vehicle. Free-feeding intake, operant lever-pressing for palatable food, energy expenditure (indirect calorimetry), and body weight were measured. GPR120 mRNA expression was measured in pertinent brain areas. Anxiety-like behavior was assessed in the elevated-plus maze and open field test. Results: GPR120 agonist injections substantially reduced chow intake during 4 hours postinjection, suppressed the rewarding effects of high-fat/-sugar food, and blunted approach-avoidance behavior in the open field. Conversely, prolonged central GPR120 agonist infusions reduced anxiety-like behavior in the elevated-plus maze and open field, yet failed to affect free-feeding intake, energy expenditure, and body weight on a high-fat diet. Conclusion: Acute reductions in food intake and food reward suggest that GPR120 could mediate the effects of central ω-3 polyunsaturated fatty acids to inhibit appetite. The anxiolytic effect elicited by GPR120 agonist infusions favors the testing of compounds that can enter the brain to activate GPR120 for the mitigation of anxiety. PMID:26888796

  15. Flexible retinal electrode array

    DOEpatents

    Okandan, Murat; Wessendorf, Kurt O.; Christenson, Todd R.

    2006-10-24

    An electrode array which has applications for neural stimulation and sensing. The electrode array can include a large number of electrodes each of which is flexibly attached to a common substrate using a plurality of springs to allow the electrodes to move independently. The electrode array can be formed from a combination of bulk and surface micromachining, with electrode tips that can include an electroplated metal (e.g. platinum, iridium, gold or titanium) or a metal oxide (e.g. iridium oxide) for biocompatibility. The electrode array can be used to form a part of a neural prosthesis, and is particularly well adapted for use in an implantable retinal prosthesis where the electrodes can be tailored to provide a uniform gentle contact pressure with optional sensing of this contact pressure at one or more of the electrodes.

  16. Retinal Injury Secondary to Laser Pointers in Pediatric Patients.

    PubMed

    Xu, Kunyong; Chin, Eric K; Quiram, Polly A; Davies, John B; Parke, D Wilkin; Almeida, David R P

    2016-10-01

    This case report describes 4 male children (age, 9-16) who had laser-related retinal injury to the macula of 1 eye or both eyes due to the mishandling of the laser pointer devices at a single vitreoretinal clinical practice. The presenting symptoms associated with laser pointer injury include central vision loss, central scotoma, and metamorphopsia. Clinical findings of laser-related retinal injury include reduced visual acuity, disruption of the photoreceptor ellipsoid zone, retinal pigment epithelium atrophy, and choroidal neovascular membrane formation. Disruption of the foveal ellipsoid zone (photoreceptor inner segment/outer segment layer) is the most common finding on optical coherence tomography imaging. Three patients had potential irreversible vision loss. Laser pointers are readily available and appropriate use of laser pointers in the pediatric population must be emphasized due to the potential irreversible retinal injury. Health professionals, school teachers, and parents should raise public awareness of this emerging public health issue by educating children about the dangers of laser pointers. Laser pointer devices among children should be discouraged and limited due to the possibility of permanent harm to themselves and others. Legislation and laws may be required to better control the sale and use of these devices.

  17. Vitreal Ocygenation in Retinal Ischemia Reperfusion

    SciTech Connect

    Abdallab, Walid; AmeriMD, Hossein; Barron, Ernesto; ChaderPhD, Gerald; Greenbaum, Elias; Hinton, David E; Humayun, Mark S

    2011-01-01

    PURPOSE. To study the feasibility of anterior vitreal oxygenation for the treatment of acute retinal ischemia. METHODS. Twenty rabbits were randomized into an oxygenation group, a sham treatment group, and a no treatment group. Baseline electroretinography (ERG) and preretinal oxygen (PO2) measurements were obtained 3 to 5 days before surgery. Intraocular pressure was raised to 100 mm Hg for 90 minutes and then normalized. The oxygenation group underwent vitreal oxygenation for 30 minutes using intravitreal electrodes. The sham treatment group received inactive electrodes for 30 minutes while there was no intervention for the no treatment group. Preretinal PO2 in the posterior vitreous was measured 30 minutes after intervention or 30 minutes after reperfusion (no treatment group) and on postoperative days (d) 3, 6, 9, and 12. On d14, rabbits underwent ERG and were euthanatized.

  18. The Development of a Cat Model of Retinal Detachment and Re-attachment.

    PubMed

    Wassmer, Sarah; Leonard, Brian C; Coupland, Stuart G; Baker, Adam; Hamilton, John; Torlone, Renée; Zacks, David N; Tsilfidis, Catherine

    2016-01-01

    We present an optimized surgical technique for feline retinal detachment which allows for natural re-attachment, reduces retinal scarring and vitreal bands, and allows central placement of the detachment in close proximity to the optic nerve. This enables imaging via Optical Coherence Tomography (OCT) and multifocal electroretinography (mfERG) analysis. Ideal detachment conditions involve a lensectomy followed by a three-port pars plana vitrectomy. A 16-20 % retinal detachment is induced by injecting 8 % C3F8 gas into the subretinal space in the central retina with a 42G cannula. The retinal detachment resolves approximately 6 weeks post-surgery. Imaging is enhanced by using a 7.5 and 20 diopter lens for OCT and mfERG fundus imaging, respectively, to compensate for the removed lens.

  19. Retinal Flip in Rhodopsin Activation?

    PubMed Central

    Feng, Jun; Brown, Michael F.; Mertz, Blake

    2015-01-01

    Rhodopsin is a well-characterized structural model of a G protein-coupled receptor. Photoisomerization of the covalently bound retinal triggers activation. Surprisingly, the x-ray crystal structure of the active Meta-II state has a 180° rotation about the long-axis of the retinal polyene chain. Unbiased microsecond-timescale all-atom molecular dynamics simulations show that the retinal cofactor can flip back to the orientation observed in the inactive state of rhodopsin under conditions favoring the Meta-I state. Our results provide, to our knowledge, the first evidence from molecular dynamics simulations showing how rotation of the retinal ligand within its binding pocket can occur in the activation mechanism of rhodopsin. PMID:26083914

  20. Protein Misfolding and Retinal Degeneration

    PubMed Central

    Tzekov, Radouil; Stein, Linda; Kaushal, Shalesh

    2011-01-01

    The retina is a highly complex and specialized organ that performs preliminary analysis of visual information. Composed of highly metabolically active tissue, the retina requires a precise and well-balanced means of maintaining its functional activity during extended periods of time. Maintenance and regulation of a vast array of different structural and functional proteins is required for normal function of the retina. This process is referred to as protein homeostasis and involves a variety of activities, including protein synthesis, folding, transport, degradation, elimination, and recycling. Deregulation of any of these activities can lead to malfunctioning of the retina, from subtle subclinical signs to severe retinal degenerative diseases leading to blindness. Examples of retinal degenerative diseases caused by disruption of protein homeostasis include retinitis pigmentosa and Stargardt’s disease. A detailed discussion of the role of disruption in protein homeostasis in these and other retinal diseases is presented, followed by examples of some existing and potential treatments. PMID:21825021

  1. General Pathophysiology in Retinal Degeneration

    PubMed Central

    Wert, Katherine J.; Lin, Jonathan H.; Tsang, Stephen H.

    2015-01-01

    Retinal degeneration, including that seen in age-related macular degeneration and retinitis pigmentosa (RP), is the most common form of neural degenerative disease in the world. There is great genetic and allelic heterogeneity of the various retinal dystrophies. Classifications of these diseases can be ambiguous, as there are similar clinical presentations in retinal degenerations arising from different genetic mechanisms. As would be expected, alterations in the activity of the phototransduction cascade, such as changes affecting the renewal and shedding of the photoreceptor OS, visual transduction, and/ or retinol metabolism have a great impact on the health of the retina. Mutations within any of the molecules responsible for these visual processes cause several types of retinal and retinal pigment epithelium degenerative diseases. Apoptosis has been implicated in the rod cell loss seen in a mouse model of RP, but the precise mechanisms that connect the activation of these pathways to the loss of phosphodiesterase (PDE6β) function has yet to be defined. Additionally, the activation of apoptosis by CCAAT/-enhancer-binding protein homologous protein (CHOP), after activation of the unfolded protein response pathway, may be responsible for cell death, although the mechanism remains unknown. However, the mechanisms of cell death after loss of function of PDE6, which is a commonly studied mammalian model in research, may be generalizable to loss of function of different key proteins involved in the phototransduction cascade. PMID:24732759

  2. Retinal implants: a systematic review.

    PubMed

    Chuang, Alice T; Margo, Curtis E; Greenberg, Paul B

    2014-07-01

    Retinal implants present an innovative way of restoring sight in degenerative retinal diseases. Previous reviews of research progress were written by groups developing their own devices. This systematic review objectively compares selected models by examining publications describing five representative retinal prostheses: Argus II, Boston Retinal Implant Project, Epi-Ret 3, Intelligent Medical Implants (IMI) and Alpha-IMS (Retina Implant AG). Publications were analysed using three criteria for interim success: clinical availability, vision restoration potential and long-term biocompatibility. Clinical availability: Argus II is the only device with FDA approval. Argus II and Alpha-IMS have both received the European CE Marking. All others are in clinical trials, except the Boston Retinal Implant, which is in animal studies. Vision restoration: resolution theoretically correlates with electrode number. Among devices with external cameras, the Boston Retinal Implant leads with 100 electrodes, followed by Argus II with 60 electrodes and visual acuity of 20/1262. Instead of an external camera, Alpha-IMS uses a photodiode system dependent on natural eye movements and can deliver visual acuity up to 20/546. Long-term compatibility: IMI offers iterative learning; Epi-Ret 3 is a fully intraocular device; Alpha-IMS uses intraocular photosensitive elements. Merging the results of these three criteria, Alpha-IMS is the most likely to achieve long-term success decades later, beyond current clinical availability.

  3. Retinal oxygen extraction in humans

    NASA Astrophysics Data System (ADS)

    Werkmeister, René M.; Schmidl, Doreen; Aschinger, Gerold; Doblhoff-Dier, Veronika; Palkovits, Stefan; Wirth, Magdalena; Garhöfer, Gerhard; Linsenmeier, Robert A.; Leitgeb, Rainer A.; Schmetterer, Leopold

    2015-10-01

    Adequate function of the retina is dependent on proper oxygen supply. In humans, the inner retina is oxygenated via the retinal circulation. We present a method to calculate total retinal oxygen extraction based on measurement of total retinal blood flow using dual-beam bidirectional Doppler optical coherence tomography and measurement of oxygen saturation by spectrophotometry. These measurements were done on 8 healthy subjects while breathing ambient room air and 100% oxygen. Total retinal blood flow was 44.3 ± 9.0 μl/min during baseline and decreased to 18.7 ± 4.2 μl/min during 100% oxygen breathing (P < 0.001) resulting in a pronounced decrease in retinal oxygen extraction from 2.33 ± 0.51 μl(O2)/min to 0.88 ± 0.14 μl(O2)/min during breathing of 100% oxygen. The method presented in this paper may have significant potential to study oxygen metabolism in hypoxic retinal diseases such as diabetic retinopathy.

  4. Retinal oxygen extraction in humans

    PubMed Central

    Werkmeister, René M.; Schmidl, Doreen; Aschinger, Gerold; Doblhoff-Dier, Veronika; Palkovits, Stefan; Wirth, Magdalena; Garhöfer, Gerhard; Linsenmeier, Robert A.; Leitgeb, Rainer A.; Schmetterer, Leopold

    2015-01-01

    Adequate function of the retina is dependent on proper oxygen supply. In humans, the inner retina is oxygenated via the retinal circulation. We present a method to calculate total retinal oxygen extraction based on measurement of total retinal blood flow using dual-beam bidirectional Doppler optical coherence tomography and measurement of oxygen saturation by spectrophotometry. These measurements were done on 8 healthy subjects while breathing ambient room air and 100% oxygen. Total retinal blood flow was 44.3 ± 9.0 μl/min during baseline and decreased to 18.7 ± 4.2 μl/min during 100% oxygen breathing (P < 0.001) resulting in a pronounced decrease in retinal oxygen extraction from 2.33 ± 0.51 μl(O2)/min to 0.88 ± 0.14 μl(O2)/min during breathing of 100% oxygen. The method presented in this paper may have significant potential to study oxygen metabolism in hypoxic retinal diseases such as diabetic retinopathy. PMID:26503332

  5. Optic neuritis heralding varicella zoster virus retinitis in a patient with acquired immunodeficiency syndrome.

    PubMed

    Meenken, C; van den Horn, G J; de Smet, M D; van der Meer, J T

    1998-04-01

    We report on a 29-year-old severely compromised acquired immunodeficiency syndrome patient who developed retrobulbar optic neuritis 5 weeks after an episode of cutaneous herpes zoster infection. During the optic neuritis, varicella zoster virus could be demonstrated in the cerebrospinal fluid. The neuritis responded well to treatment with foscarnet, but, 3 weeks into therapy, varicella zoster retinitis developed. Additional treatment with intravenous acyclovir stopped progression of the retinitis and resulted in healing of the retinal lesions. This case suggests that retrobulbar optic neuritis can be regarded as a prodrome of imminent acute retinal necrosis. Early recognition and prompt therapy with combined antivirals may prevent the development of this devastating ocular complication of varicella zoster infection.

  6. A case of atypical progressive outer retinal necrosis after highly active antiretroviral therapy.

    PubMed

    Woo, Se Joon; Yu, Hyeong Gon; Chung, Hum

    2004-06-01

    This is a report of an atypical case of progressive outer retinal necrosis (PORN) and the effect of highly active antiretroviral therapy (HAART) on the clinical course of viral retinitis in an acquired immunodeficiency syndrome (AIDS) patient. A 22-year-old male patient infected with human immunodeficiency virus (HIV) presented with unilaterally reduced visual acuity and a dense cataract. After cataract extraction, retinal lesions involving the peripheral and macular areas were found with perivascular sparing and the mud-cracked, characteristic appearance of PORN. He was diagnosed as having PORN based on clinical features and was given combined antiviral treatment. With concurrent HAART, the retinal lesions regressed, with the regression being accelerated by further treatment with intravenous acyclovir and ganciclovir. This case suggests that HAART may change the clinical course of PORN in AIDS patients by improving host immunity. PORN should be included in the differential diagnosis of acute unilateral cataract in AIDS patients.

  7. Increased Expression of Osteopontin in Retinal Degeneration Induced by Blue Light-Emitting Diode Exposure in Mice

    PubMed Central

    Chang, Seung Wook; Kim, Hyung Il; Kim, Gyu Hyun; Park, Su Jin; Kim, In-Beom

    2016-01-01

    Osteopontin (OPN) is a multifunctional adhesive glycoprotein that is implicated in a variety of pro-inflammatory as well as neuroprotective and repair-promoting effects in the brain. As a first step towards understanding the role of OPN in retinal degeneration (RD), we examined changes in OPN expression in a mouse model of RD induced by exposure to a blue light-emitting diode (LED). RD was induced in BALB/c mice by exposure to a blue LED (460 nm) for 2 h. Apoptotic cell death was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. In order to investigate changes in OPN in RD, western blotting and immunohistochemistry were performed. Anti-OPN labeling was compared to that of anti-glial fibrillary acidic protein (GFAP), which is a commonly used marker for retinal injury or stress including inflammation. OPN expression in RD retinas markedly increased at 24 h after exposure, was sustained through 72 h, and subsided at 120 h. Increased OPN expression was observed co-localized with microglial cells in the outer nuclear layer (ONL), outer plexiform layer (OPL), and subretinal space. Expression was restricted to the central retina in which photoreceptor cell death occurred. Interestingly, OPN expression in the ONL/OPL was closely associated with microglia, whereas most of the OPN plaques observed in the subretinal space were not. Immunogold electron microscopy demonstrated that OPN was distributed throughout the cytoplasm of microglia and in nearby fragments of degenerating photoreceptors. In addition, we found that OPN was induced more acutely and with greater region specificity than GFAP. These results indicate that OPN may be a more useful marker for retinal injury or stress, and furthermore act as a microglial pro-inflammatory mediator and a phagocytosis-inducing opsonin in the subretinal space. Taken together, our data suggest that OPN plays an important role in the pathogenesis of RD. PMID:27504084

  8. Central responsiveness to a ghrelin mimetic (GHRP-6) is rapidly altered by acute changes in nutritional status in rats.

    PubMed

    Tung, Y C L; Hewson, A K; Carter, R N; Dickson, S L

    2005-06-01

    The hypothalamus appears to be more responsive to ghrelin and growth hormone secretagogues (GHS) in fasting, as reflected by a two- to three-fold increase in the number of cells detected that express Fos protein in the arcuate nucleus, in 48-h fasted rats compared to fed controls. Moreover, this increased hypothalamic responsiveness to GHS in fasting is regulated by the central action of exogenous leptin and insulin, although it is unknown whether these hormones mediate the changes in hypothalamic responsiveness to GHS associated with the fasting/fed state. In the present study, we show that refeeding with normal rat chow for only 2 h at the end of a 48-h fast reversed the potentiation of the Fos response to GHRP-6 observed in fasted rats. Circulating leptin and insulin levels remained significantly lower in refed rats compared to ad lib-fed rats, suggesting that the change in the hypothalamic sensitivity brought about by refeeding was independent of these hormones. By contrast, 2 h of chow refeeding at the end of a fast restored plasma glucose levels to those of the fed state. Refeeding with sugar alone for 2 h at the end of a 48-h fast also reduced the potentiated Fos response in fasting, indicating that elevated blood glucose can influence the central responsiveness to ghrelin/GHS. By contrast, infusion of the ileal satiety factor, PYY(3-36) (known to increase postprandially) did not alter the central responsiveness to GHRP-6, although it suppressed feeding and body weight as expected. This study highlights the importance of nutritional status in regulating the action of exogenous GHS (and presumably endogenous ghrelin) on the hypothalamic circuits controlling food intake.

  9. Developing Cellular Therapies for Retinal Degenerative Diseases

    PubMed Central

    Bharti, Kapil; Rao, Mahendra; Hull, Sara Chandros; Stroncek, David; Brooks, Brian P.; Feigal, Ellen; van Meurs, Jan C.; Huang, Christene A.; Miller, Sheldon S.

    2014-01-01

    Biomedical advances in vision research have been greatly facilitated by the clinical accessibility of the visual system, its ease of experimental manipulation, and its ability to be functionally monitored in real time with noninvasive imaging techniques at the level of single cells and with quantitative end-point measures. A recent example is the development of stem cell–based therapies for degenerative eye diseases including AMD. Two phase I clinical trials using embryonic stem cell–derived RPE are already underway and several others using both pluripotent and multipotent adult stem cells are in earlier stages of development. These clinical trials will use a variety of cell types, including embryonic or induced pluripotent stem cell–derived RPE, bone marrow– or umbilical cord–derived mesenchymal stem cells, fetal neural or retinal progenitor cells, and adult RPE stem cells–derived RPE. Although quite distinct, these approaches, share common principles, concerns and issues across the clinical development pipeline. These considerations were a central part of the discussions at a recent National Eye Institute meeting on the development of cellular therapies for retinal degenerative disease. At this meeting, emphasis was placed on the general value of identifying and sharing information in the so-called “precompetitive space.” The utility of this behavior was described in terms of how it could allow us to remove road blocks in the clinical development pipeline, and more efficiently and economically move stem cell–based therapies for retinal degenerative diseases toward the clinic. Many of the ocular stem cell approaches we discuss are also being used more broadly, for nonocular conditions and therefore the model we develop here, using the precompetitive space, should benefit the entire scientific community. PMID:24573369

  10. Acute functional reorganisation of the human motor cortex during resection of central lesions: a study using intraoperative brain mapping

    PubMed Central

    Duffau, H

    2001-01-01

    OBJECTIVES—Brain plasticity is supposed to allow the compensation of motor function in cases of rolandic lesion. The aim was to analyse the mechanisms of functional reorganisation during surgery in the central area.
METHODS—A motor brain mapping was performed in three right handed patients without any neurological deficit, operated on for a slow growing lesion near the rolandic region (two precentral resected under general anaesthesia and one retrocentral removed under local anaesthesia to allow also sensory mapping) using intraoperative direct electrical stimulations (5 mm space tips bipolar stimulator probe, biphasic square wave pulse current: 1 ms/phase, 60 Hz, 4 to 18mA).
RESULTS—For each patient, the motor areas of the hand and forearm in the primary motor cortex (M1) were identified before and after lesion removal with the same stimulation parameters: the same eloquent sites were found, plus the appearance after resection of additional sites in M1 inducing the same movement during stimulations as the previous areas.
CONCLUSIONS—Multiple cortical representations for hand and forearm movements in M1 seem to exist. In addition, the results demonstrate the short term capacity of the brain to make changes in local motor maps, by sudden unmasking after tumour resection of a second redundant site participating in the same movement. Finally, it seems not necessary for the whole of the redundant sites to be functional to provide normal movement, a concept with potential implications for surgery within the central region.

 PMID:11254775

  11. [Treatment of obstruction of retinal vessels (author's transl)].

    PubMed

    Babel, J

    1977-02-01

    The treatment of retinal thrombosis is an unresolved problem, mainly because of the numerous factors which participate in their formation; modifications in the walls of veins and arteries, external compressions, changes in the blood count--particularly of the platelets--slowing down of the blood flow, increase in blood viscosity etc. No drug provides constant results. Some widely employed drugs such as vasodilators may be useless or even contra-indicated. Emphasis is placed on anti-coagulants, fibrinolytics, antiaggregating agents and methods of lowering blood viscosity. Their action is difficult to test objectively. Some do appear to be useful, especially in cases of central vein thrombosis. Thrombi of branches of the central vein are apparently inacessible to medical therapy, but occasionally improvement is seen after laser coagulation. This seems to apply also to hemorrhagic glaucoma secondary to retinal obstruction.

  12. Optoelectronic retinal prosthesis: system design and performance.

    PubMed

    Loudin, J D; Simanovskii, D M; Vijayraghavan, K; Sramek, C K; Butterwick, A F; Huie, P; McLean, G Y; Palanker, D V

    2007-03-01

    The design of high-resolution retinal prostheses presents many unique engineering and biological challenges. Ever smaller electrodes must inject enough charge to stimulate nerve cells, within electrochemically safe voltage limits. Stimulation sites should be placed within an electrode diameter from the target cells to prevent 'blurring' and minimize current. Signals must be delivered wirelessly from an external source to a large number of electrodes, and visual information should, ideally, maintain its natural link to eye movements. Finally, a good system must have a wide range of stimulation currents, external control of image processing and the option of either anodic-first or cathodic-first pulses. This paper discusses these challenges and presents solutions to them for a system based on a photodiode array implant. Video frames are processed and imaged onto the retinal implant by a head-mounted near-to-eye projection system operating at near-infrared wavelengths. Photodiodes convert light into pulsed electric current, with charge injection maximized by applying a common biphasic bias waveform. The resulting prosthesis will provide stimulation with a frame rate of up to 50 Hz in a central 10 degrees visual field, with a full 30 degrees field accessible via eye movements. Pixel sizes are scalable from 100 to 25 microm, corresponding to 640-10,000 pixels on an implant 3 mm in diameter.

  13. Retinal AO OCT

    NASA Astrophysics Data System (ADS)

    Zawadzki, Robert J.; Miller, Donald T.

    The last two decades have witnessed extraordinary advances in optical technology to image noninvasively and at high resolution the posterior segment of the eye. Two of the most impactful technological advancements over this period have arguably been optical coherence tomography (OCT) and adaptive optics (AO). The strengths of these technologies complement each other and when combined have been shown to provide unprecedented, micron-scale resolution (<3 μm) in all three dimensions and sensitivity to image the cellular retina in the living eye. This powerful extension of OCT, that is AO-OCT, is the focus of this chapter. It presents key aspects of designing and implementing AO-OCT systems. Particular attention is devoted to the relevant optical properties of the eye that ultimately define these systems, AO componentry and operation tailored for ophthalmic use, and of course use of the latest technologies and methods in OCT for ocular imaging. It surveys the wide range of AO-OCT designs that have been developed for retinal imaging, with AO integrated into every major OCT design configuration. Finally, it reviews the scientific and clinical studies reported to date that show the exciting potential of AO-OCT to image the microscopic retina and fundus in ways not previously possible with other noninvasive methods and a look to future developments in this rapidly growing field.

  14. Eye Morphology and Retinal Topography in Hummingbirds (Trochilidae: Aves).

    PubMed

    Lisney, Thomas J; Wylie, Douglas R; Kolominsky, Jeffrey; Iwaniuk, Andrew N

    2015-01-01

    Hummingbirds are a group of small, highly specialized birds that display a range of adaptations to their nectarivorous lifestyle. Vision plays a key role in hummingbird feeding and hovering behaviours, yet very little is known about the visual systems of these birds. In this study, we measured eye morphology in 5 hummingbird species. For 2 of these species, we used stereology and retinal whole mounts to study the topographic distribution of neurons in the ganglion cell layer. Eye morphology (expressed as the ratio of corneal diameter to eye transverse diameter) was similar among all 5 species and was within the range previously documented for diurnal birds. Retinal topography was similar in Amazilia tzacatl and Calypte anna. Both species had 2 specialized retinal regions of high neuron density: a central region located slightly dorso-nasal to the superior pole of the pecten, where densities reached ∼ 45,000 cells · mm(-2), and a temporal area with lower densities (38,000-39,000 cells · mm(-2)). A weak visual streak bridged the two high-density areas. A retina from Phaethornis superciliosus also had a central high-density area with a similar peak neuron density. Estimates of spatial resolving power for all 3 species were similar, at approximately 5-6 cycles · degree(-1). Retinal cross sections confirmed that the central high-density region in C. anna contains a fovea, but not the temporal area. We found no evidence of a second, less well-developed fovea located close to the temporal retina margin. The central and temporal areas of high neuron density allow for increased spatial resolution in the lateral and frontal visual fields, respectively. Increased resolution in the frontal field in particular may be important for mediating feeding behaviors such as aerial docking with flowers and catching small insects.

  15. Study of retinal vessel oxygen saturation in ischemic and non-ischemic branch retinal vein occlusion

    PubMed Central

    Lin, Lei-Lei; Dong, Yan-Min; Zong, Yao; Zheng, Qi-Shan; Fu, Yue; Yuan, Yong-Guang; Huang, Xia; Qian, Garrett; Gao, Qian-Ying

    2016-01-01

    AIM To explore how oxygen saturation in retinal blood vessels is altered in ischemic and non-ischemic branch retinal vein occlusion (BRVO). METHODS Fifty BRVO eyes were divided into ischemic (n=26) and non-ischemic (n=24) groups, based on fundus fluorescein angiography. Healthy individuals (n=52 and n=48, respectively) were also recruited as controls for the two groups. The mean oxygen saturations of the occluded vessels and central vessels were measured by oximetry in the BRVO and control groups. RESULTS In the ischemic BRVO group, the occluded arterioles oxygen saturation (SaO2-A, 106.0%±14.3%), instead of the occluded venule oxygen saturation (SaO2-V, 60.8%±9.4%), showed increases when compared with those in the same quadrant vessels (SaO2-A, 86.1%±16.5%) in the contralateral eyes (P<0.05). The oxygen saturations of the central vessels showed similar trends with those of the occluded vessels. In the non-ischemic BRVO group, the occluded and central SaO2-V and SaO2-A showed no significant changes. In both the ischemic and non-ischemic BRVOs, the central SaO2-A was significantly increased when compared to healthy individuals. CONCLUSION Obvious changes in the occluded and central SaO2-A were found in the ischemic BRVO group, indicating that disorders of oxygen metabolism in the arterioles may participate in the pathogenesis of ischemic BRVO. PMID:26949618

  16. Rhegmatogenous retinal detachment treatment guidelines.

    PubMed

    García-Arumí, J; Martínez-Castillo, V; Boixadera, A; Blasco, H; Marticorena, J; Zapata, M Á; Macià, C; Badal, J; Distéfano, L; Rafart, J M; Berrocal, M; Zambrano, A; Ruíz-Moreno, J M; Figueroa, M S

    2013-01-01

    This paper outlines general guidelines following the initial diagnosis of rhegmatogenous retinal detachment. These include preoperative evaluation, treatment, possible intra- and post-operative complications, retinal re-detachment, and all therapeutic options available for each case. Treatment of the traumatic retinal detachment is also described, due to its importance and peculiarities. Treatment or prophylactic guidelines are suggested for the different types of retinal detachment described. These are based on both the experience of the ophthalmologists that have participated in preparing the guidelines, and also on evidence-based grading linked to bibliographical sources. However, these guidelines should not be interpreted as being mandatory. Given that there is a wide spectrum of options for treatment of retinal detachment, the surgeons' experience with one or other surgical technique will be of utmost importance in obtaining the best surgical result. As guidelines, they are intended as an additional aid to the surgeon during the decision-making process, with the expectation that the final choice will still be left to the surgeon's judgment and past experience.

  17. The influence of vasopressin deficiency and acute desmopressin administration on melatonin secretion in patients with central diabetes insipidus.

    PubMed

    Catrina, S B; Rotarus, R; Wivall, I-L; Coculescu, M; Brismar, K

    2004-01-01

    Melatonin secretion is modulated by the light-dark schedule, mainly through a sympathetic input to the pineal gland. Besides this, arginine vasopressin (AVP) has been found in the pineal glands of several animal species and there is experimental evidence that AVP modulates melatonin secretion in animals. However, the interaction between vasopressin and melatonin secretion in humans has not been systematically investigated. We proposed to study the nocturnal melatonin pattern in patients with central diabetes insipidus (CDI) who lack endogenous secretion of AVP, and the effect on their melatonin secretion of the agonist for V2 type receptors: desmopressin (1-Desamino [8-D Arginine] vasopressin). Plasma melatonin levels were measured in 14 patients with CDI, every 2 h starting from 22:00 h until 06:00 h, following iv injection of saline (day 1) and 3 microg desmopressin (day 2) at 20:00 h. The lights were turned off at 22:30 h and the samples were taken in a dim light. The plasma melatonin secretion pattern was normal in patients with CDI. Desmopressin at a dose 3 times higher than the antidiuretic one did not modify the melatonin levels or the time of the peak secretion. In conclusion melatonin secretion is not modulated by AVP in humans.

  18. SUMOylation of NaV1.2 channels mediates the early response to acute hypoxia in central neurons

    PubMed Central

    Plant, Leigh D; Marks, Jeremy D; Goldstein, Steve AN

    2016-01-01

    The mechanism for the earliest response of central neurons to hypoxia—an increase in voltage-gated sodium current (INa)—has been unknown. Here, we show that hypoxia activates the Small Ubiquitin-like Modifier (SUMO) pathway in rat cerebellar granule neurons (CGN) and that SUMOylation of NaV1.2 channels increases INa. The time-course for SUMOylation of single NaV1.2 channels at the cell surface and changes in INa coincide, and both are prevented by mutation of NaV1.2-Lys38 or application of a deSUMOylating enzyme. Within 40 s, hypoxia-induced linkage of SUMO1 to the channels is complete, shifting the voltage-dependence of channel activation so that depolarizing steps evoke larger sodium currents. Given the recognized role of INa in hypoxic brain damage, the SUMO pathway and NaV1.2 are identified as potential targets for neuroprotective interventions. DOI: http://dx.doi.org/10.7554/eLife.20054.001 PMID:28029095

  19. [Congenital retinal folds in different clinical cases].

    PubMed

    Munteanu, M

    2005-01-01

    We present 12 clinical cases of congenital retinal folds with different etiologies: posterior primitive vitreous persistency and hyperplasia (7 cases),retinocytoma (1 case). retinopathy of prematurity (1 case), astrocytoma of the retina (1 case), retinal vasculitis (1 case), Goldmann-Favre syndrome (1 case). Etiopathogenic and nosological aspects are discussed; the congenital retinal folds are interpreted as a symptom in a context of a congenital or acquired vitreo-retinal pathology.

  20. [Unusual retinal abnormality: retinal hemorrhages related to scurvy].

    PubMed

    Errera, M-H; Dupas, B; Man, H; Gualino, V; Gaudric, A; Massin, P

    2011-03-01

    A diet restricted to rice and boiled fruit and vegetables leads to vitamin C deficiency. We describe the third case, to our knowledge, of retinal hemorrhages related to scurvy. Reduced bilateral visual acuity in a 50-year-old patient was associated with macrocytic anemia, denutrition, and cutaneous ecchymoses. Oral vitamin C treatment provided subjective clinical improvement and regression of the retinal hemorrhages on fundus examination, with no side effects. Vitamin C plays an important role in collagen stability in vascular and bone walls.

  1. An excitatory cortical feedback loop gates retinal wave transmission in rodent thalamus

    PubMed Central

    Murata, Yasunobu; Colonnese, Matthew T

    2016-01-01

    Spontaneous retinal waves are critical for the development of receptive fields in visual thalamus (LGN) and cortex (VC). Despite a detailed understanding of the circuit specializations in retina that generate waves, whether central circuit specializations also exist to control their propagation through visual pathways of the brain is unknown. Here we identify a developmentally transient, corticothalamic amplification of retinal drive to thalamus as a mechanism for retinal wave transmission in the infant rat brain. During the period of retinal waves, corticothalamic connections excite LGN, rather than driving feedforward inhibition as observed in the adult. This creates an excitatory feedback loop that gates retinal wave transmission through the LGN. This cortical multiplication of retinal wave input ends just prior to eye-opening, as cortex begins to inhibit LGN. Our results show that the early retino-thalamo-cortical circuit uses developmentally specialized feedback amplification to ensure powerful, high-fidelity transmission of retinal activity despite immature connectivity. DOI: http://dx.doi.org/10.7554/eLife.18816.001 PMID:27725086

  2. Characteristic Retinal Atrophy with Secondary “Inverse” Optic Atrophy Identifies Vigabatrin Toxicity in Children

    PubMed Central

    Buncic, J. Raymond; Westall, Carol A.; Panton, Carole M.; Munn, J. Robert; MacKeen, Leslie D.; Logan, William J.

    2013-01-01

    Objective To describe the clinical pattern of retinal atrophy in children caused by the anticonvulsant vigabatrin. Design An interventional case series report. Participants One hundred thirty-eight patients, mainly infants, were evaluated regularly for evidence of possible vigabatrin toxicity in the Eye and Neurology clinics at the Hospital for Sick Children, Toronto. Method Sequential clinical and electroretinographic (International Society for Clinical Electrophysiology of Vision standards) evaluations every 6 months. Main Outcome Measures Presence of recognizable retinal and optic atrophy in the presence of abnormal electroretinogram (ERG) and other clinical findings. Results Three children being treated for seizures with vigabatrin showed definite clinical findings of peripheral retinal nerve fiber layer atrophy, with relative sparing of the central or macular portion of the retina and relative nasal optic nerve atrophic changes. Some macular wrinkling was evident in 1 case. Progressive ERG changes showing decreased responses, especially the 30-Hz flicker response, supported the presence of decreased retinal function. Conclusions A recognizable and characteristic form of peripheral retinal atrophy and nasal or “inverse” optic disc atrophy can occur in a small number of children being treated with vigabatrin. The changes in superficial light reflexes of the retina in children facilitate the clinical recognition of nerve fiber layer atrophy. The macula is relatively spared, although superficial retinal light reflexes indicating wrinkling of the innermost retina suggest early macular toxicity as well. Because these changes are accompanied by electrophysiologic evidence of retinal dysfunction, discontinuation of vigabatrin should be strongly considered. PMID:15465561

  3. Outer Retinal Structure Following Closed Globe Blunt Ocular Trauma

    PubMed Central

    Flatter, John A.; Cooper, Robert F.; Dubow, Michael J.; Pinhas, Alexander; Singh, Ravi S.; Kapur, Rashmi; Shah, Nishit; Walsh, Ryan D.; Hong, Sang H.; Weinberg, David V.; Stepien, Kimberly E.; Wirostko, William J.; Robison, Scott; Dubra, Alfredo; Rosen, Richard B.; Connor, Thomas B.; Carroll, Joseph

    2014-01-01

    Purpose To evaluate outer retinal structural abnormalities in patients with visual deficits following closed globe blunt ocular trauma (cgBOT). Methods Nine subjects with visual complaints following cgBOT were examined between 1 month post-trauma and 6 years post-trauma. Spectral domain optical coherence tomography (SD-OCT) was used to assess outer retinal architecture, while adaptive optics scanning light ophthalmoscopy (AOSLO) was used to analyze photoreceptor mosaic integrity. Results Visual deficits ranged from central scotomas to decreased visual acuity. SD-OCT defects included focal foveal photoreceptor lesions, variable attenuation of the interdigitation zone, and mottling of the outer segment band, with one subject having normal outer retinal structure. AOSLO revealed disruption of the photoreceptor mosaic in all subjects, variably manifesting as foveal focal discontinuities, perifoveal hyporeflective cones, and paracentral regions of selective cone loss. Conclusions We observe persistent outer retinal disruption in subjects with visual complaints following cgBOT, albeit to a variable degree. AOSLO imaging allows assessment of photoreceptor structure at a level of detail not resolvable using SD-OCT or other current clinical imaging tools. Multimodal imaging appears useful for revealing the cause of visual complaints in patients following cgBOT. Future studies are needed to better understand how photoreceptor structure changes longitudinally in response to various trauma. PMID:24752010

  4. Photoreceptor cell death and rescue in retinal detachment and degenerations

    PubMed Central

    Murakami, Yusuke; Notomi, Shoji; Hisatomi, Toshio; Nakazawa, Toru; Ishibashi, Tatsuro; Miller, Joan W.; Vavvas, Demetrios G.

    2013-01-01

    Photoreceptor cell death is the ultimate cause of vision loss in various retinal disorders, including retinal detachment (RD). Photoreceptor cell death has been thought to occur mainly through apoptosis, which is the most characterized form of programmed cell death. The caspase family of cysteine proteases plays a central role for inducing apoptosis, and in experimental models of RD, dying photoreceptor cells exhibit caspase activation; however, there is a paradox that caspase inhibition alone does not provide a sufficient protection against photoreceptor cell loss, suggesting that other mechanisms of cell death are involved. Recent accumulating evidence demonstrates that non-apoptotic forms of cell death, such as autophagy and necrosis, are also regulated by specific molecular machinery, such as those mediated by autophagy-related proteins and receptor-interacting protein kinases, respectively. Here we summarize the current knowledge of cell death signaling and its roles in photoreceptor cell death after RD and other retinal degenerative diseases. A body of studies indicate that not only apoptotic but also autophagic and necrotic signaling are involved in photoreceptor cell death, and that combined targeting of these pathways may be an effective neuroprotective strategy for retinal diseases associated with photoreceptor cell loss. PMID:23994436

  5. Choroidal melanoma clinically simulating a retinal angioma.

    PubMed

    Shields, J A; Joffe, L; Guibor, P

    1978-01-01

    An amelanotic fundus lesion in a 35-year-old man was associated with a dilated retinal vessel, thus suggesting the diagnosis of retinal angioma. Fluorescein angiography and B-scan ultrasonography were not diagnostic, but a radioactive phosphorus uptake test suggested the lesion was malignant. The enucleated globe showed a malignant choroidal melanoma drained by a large retinal vein.

  6. Transcorneal Electrical Stimulation Therapy for Retinal Disease

    ClinicalTrials.gov

    2012-05-03

    Retinitis Pigmentosa; Macula Off; Primary Open Angle Glaucoma; Hereditary Macular Degeneration; Treated Retina Detachment; Retinal Artery Occlusion; Retinal Vein Occlusion; Non-Arthritic-Anterior-Ischemic Optic-Neuropathy; Hereditary Autosomal Dominant Optic Atrophy; Dry Age Related Macular Degeneration; Ischemic Macula Edema

  7. Inherited Retinal Degenerative Clinical Trial Network

    DTIC Science & Technology

    2009-10-01

    ending in blindness. In the United States, the total number of individuals affected by retinitis pigmentosa (RP) and other forms of rare inherited...AD_________________ AWARD NUMBER: W81XWH-07-1-0720 TITLE: Inherited Retinal Degenerative...Final 3. DATES COVERED 27 Sep 2007 – 29 Sep 2009 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Inherited Retinal Degenerative Clinical Trial Network

  8. Exploring the retinal connectome

    PubMed Central

    Anderson, James R.; Jones, Bryan W.; Watt, Carl B.; Shaw, Margaret V.; Yang, Jia-Hui; DeMill, David; Lauritzen, James S.; Lin, Yanhua; Rapp, Kevin D.; Mastronarde, David; Koshevoy, Pavel; Grimm, Bradley; Tasdizen, Tolga; Whitaker, Ross

    2011-01-01

    Purpose A connectome is a comprehensive description of synaptic connectivity for a neural domain. Our goal was to produce a connectome data set for the inner plexiform layer of the mammalian retina. This paper describes our first retinal connectome, validates the method, and provides key initial findings. Methods We acquired and assembled a 16.5 terabyte connectome data set RC1 for the rabbit retina at ≈2 nm resolution using automated transmission electron microscope imaging, automated mosaicking, and automated volume registration. RC1 represents a column of tissue 0.25 mm in diameter, spanning the inner nuclear, inner plexiform, and ganglion cell layers. To enhance ultrastructural tracing, we included molecular markers for 4-aminobutyrate (GABA), glutamate, glycine, taurine, glutamine, and the in vivo activity marker, 1-amino-4-guanidobutane. This enabled us to distinguish GABAergic and glycinergic amacrine cells; to identify ON bipolar cells coupled to glycinergic cells; and to discriminate different kinds of bipolar, amacrine, and ganglion cells based on their molecular signatures and activity. The data set was explored and annotated with Viking, our multiuser navigation tool. Annotations were exported to additional applications to render cells, visualize network graphs, and query the database. Results Exploration of RC1 showed that the 2 nm resolution readily recapitulated well known connections and revealed several new features of retinal organization: (1) The well known AII amacrine cell pathway displayed more complexity than previously reported, with no less than 17 distinct signaling modes, including ribbon synapse inputs from OFF bipolar cells, wide-field ON cone bipolar cells and rod bipolar cells, and extensive input from cone-pathway amacrine cells. (2) The axons of most cone bipolar cells formed a distinct signal integration compartment, with ON cone bipolar cell axonal synapses targeting diverse cell types. Both ON and OFF bipolar cells receive

  9. Randomized trial of radiation-free central nervous system prophylaxis comparing intrathecal triple therapy with liposomal cytarabine in acute lymphoblastic leukemia.

    PubMed

    Bassan, Renato; Masciulli, Arianna; Intermesoli, Tamara; Audisio, Ernesta; Rossi, Giuseppe; Pogliani, Enrico Maria; Cassibba, Vincenzo; Mattei, Daniele; Romani, Claudio; Cortelezzi, Agostino; Corti, Consuelo; Scattolin, Anna Maria; Spinelli, Orietta; Tosi, Manuela; Parolini, Margherita; Marmont, Filippo; Borlenghi, Erika; Fumagalli, Monica; Cortelazzo, Sergio; Gallamini, Andrea; Marfisi, Rosa Maria; Oldani, Elena; Rambaldi, Alessandro

    2015-06-01

    Developing optimal radiation-free central nervous system prophylaxis is a desirable goal in acute lymphoblastic leukemia, to avoid the long-term toxicity associated with cranial irradiation. In a randomized, phase II trial enrolling 145 adult patients, we compared intrathecal liposomal cytarabine (50 mg: 6/8 injections in B-/T-cell subsets, respectively) with intrathecal triple therapy (methotrexate/cytarabine/prednisone: 12 injections). Systemic therapy included methotrexate plus cytarabine or L-asparaginase courses, with methotrexate augmented to 2.5 and 5 g/m(2) in Philadelphia-negative B- and T-cell disease, respectively. The primary study objective was the comparative assessment of the risk/benefit ratio, combining the analysis of feasibility, toxicity and efficacy. In the liposomal cytarabine arm 17/71 patients (24%) developed grade 3-4 neurotoxicity compared to 2/74 (3%) in the triple therapy arm (P=0.0002), the median number of episodes of neurotoxicity of any grade was one per patient compared to zero, respectively (P=0.0001), and even though no permanent disabilities or deaths were registered, four patients (6%) discontinued intrathecal prophylaxis on account of these toxic side effects (P=0.06). Neurotoxicity worsened with liposomal cytarabine every 14 days (T-cell disease), and was improved by the adjunct of intrathecal dexamethasone. Two patients in the liposomal cytarabine arm suffered from a meningeal relapse (none with T-cell disease, only one after high-dose chemotherapy) compared to four in the triple therapy arm (1 with T-cell disease). While intrathecal liposomal cytarabine could contribute to improved, radiation-free central nervous system prophylaxis, the toxicity reported in this trial does not support its use at 50 mg and prompts the investigation of a lower dosage. (clinicaltrials.gov identifier: NCT-00795756).

  10. Randomized trial of radiation-free central nervous system prophylaxis comparing intrathecal triple therapy with liposomal cytarabine in acute lymphoblastic leukemia

    PubMed Central

    Bassan, Renato; Masciulli, Arianna; Intermesoli, Tamara; Audisio, Ernesta; Rossi, Giuseppe; Pogliani, Enrico Maria; Cassibba, Vincenzo; Mattei, Daniele; Romani, Claudio; Cortelezzi, Agostino; Corti, Consuelo; Scattolin, Anna Maria; Spinelli, Orietta; Tosi, Manuela; Parolini, Margherita; Marmont, Filippo; Borlenghi, Erika; Fumagalli, Monica; Cortelazzo, Sergio; Gallamini, Andrea; Marfisi, Rosa Maria; Oldani, Elena; Rambaldi, Alessandro

    2015-01-01

    Developing optimal radiation-free central nervous system prophylaxis is a desirable goal in acute lymphoblastic leukemia, to avoid the long-term toxicity associated with cranial irradiation. In a randomized, phase II trial enrolling 145 adult patients, we compared intrathecal liposomal cytarabine (50 mg: 6/8 injections in B-/T-cell subsets, respectively) with intrathecal triple therapy (methotrexate/cytarabine/prednisone: 12 injections). Systemic therapy included methotrexate plus cytarabine or L-asparaginase courses, with methotrexate augmented to 2.5 and 5 g/m2 in Philadelphia-negative B- and T-cell disease, respectively. The primary study objective was the comparative assessment of the risk/benefit ratio, combining the analysis of feasibility, toxicity and efficacy. In the liposomal cytarabine arm 17/71 patients (24%) developed grade 3–4 neurotoxicity compared to 2/74 (3%) in the triple therapy arm (P=0.0002), the median number of episodes of neurotoxicity of any grade was one per patient compared to zero, respectively (P=0.0001), and even though no permanent disabilities or deaths were registered, four patients (6%) discontinued intrathecal prophylaxis on account of these toxic side effects (P=0.06). Neurotoxicity worsened with liposomal cytarabine every 14 days (T-cell disease), and was improved by the adjunct of intrathecal dexamethasone. Two patients in the liposomal cytarabine arm suffered from a meningeal relapse (none with T-cell disease, only one after high-dose chemotherapy) compared to four in the triple therapy arm (1 with T-cell disease). While intrathecal liposomal cytarabine could contribute to improved, radiation-free central nervous system prophylaxis, the toxicity reported in this trial does not support its use at 50 mg and prompts the investigation of a lower dosage. (clinicaltrials.gov identifier: NCT-00795756). PMID:25749825

  11. Clinical Trials in Retinal Dystrophies

    PubMed Central

    Grob, Seanna R.; Finn, Avni; Papakostas, Thanos D.; Eliott, Dean

    2016-01-01

    Research development is burgeoning for genetic and cellular therapy for retinal dystrophies. These dystrophies are the focus of many research efforts due to the unique biology and accessibility of the eye, the transformative advances in ocular imaging technology that allows for in vivo monitoring, and the potential benefit people would gain from success in the field – the gift of renewed sight. Progress in the field has revealed the immense complexity of retinal dystrophies and the challenges faced by researchers in the development of this technology. This study reviews the current trials and advancements in genetic and cellular therapy in the treatment of retinal dystrophies and also discusses the current and potential future challenges. PMID:26957839

  12. Rat retinal transcriptome

    PubMed Central

    Kozhevnikova, Oyuna S.; Korbolina, Elena E.; Ershov, Nikita I.; Kolosova, Natalia G.

    2013-01-01

    Pathogenesis of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly, remains poorly understood due to the paucity of animal models that fully replicate the human disease. Recently, we showed that senescence-accelerated OXYS rats develop a retinopathy similar to human AMD. To identify alterations in response to normal aging and progression of AMD-like retinopathy, we compared gene expression profiles of retina from 3- and 18-mo-old OXYS and control Wistar rats by means of high-throughput RNA sequencing (RNA-Seq). We identified 160 and 146 age-regulated genes in Wistar and OXYS retinas, respectively. The majority of them are related to the immune system and extracellular matrix turnover. Only 24 age-regulated genes were common for the two strains, suggestive of different rates and mechanisms of aging. Over 600 genes showed significant differences in expression between the two strains. These genes are involved in disease-associated pathways such as immune response, inflammation, apoptosis, Ca2+ homeostasis and oxidative stress. The altered expression for selected genes was confirmed by qRT-PCR analysis. To our knowledge, this study represents the first analysis of retinal transcriptome from young and old rats with biologic replicates generated by RNA-Seq technology. We can conclude that the development of AMD-like retinopathy in OXYS rats is associated with an imbalance in immune and inflammatory responses. Aging alters the expression profile of numerous genes in the retina, and the genetic background of OXYS rats has a profound impact on the development of AMD-like retinopathy. PMID:23656783

  13. Retinal Optical Coherence Tomography Imaging

    NASA Astrophysics Data System (ADS)

    Drexler, Wolfgang; Fujimoto, James G.

    The eye is essentially transparent, transmitting light with only minimal optical attenuation and scattering providing easy optical access to the anterior segment as well as the retina. For this reason, ophthalmic and especially retinal imaging has been not only the first but also most successful clinical application for optical coherence tomography (OCT). This chapter focuses on the development of OCT technology for retinal imaging. OCT has significantly improved the potential for early diagnosis, understanding of retinal disease pathogenesis, as well as monitoring disease progression and response to therapy. Development of ultrabroad bandwidth light sources and high-speed detection techniques has enabled significant improvements in ophthalmic OCT imaging performance, demonstrating the potential of three-dimensional, ultrahigh-resolution OCT (UHR OCT) to perform noninvasive optical biopsy of the living human retina, i.e., the in vivo visualization of microstructural, intraretinal morphology in situ approaching the resolution of conventional histopathology. Significant improvements in axial resolution and speed not only enable three-dimensional rendering of retinal volumes but also high-definition, two-dimensional tomograms, topographic thickness maps of all major intraretinal layers, as well as volumetric quantification of pathologic intraretinal changes. These advances in OCT technology have also been successfully applied in several animal models of retinal pathologies. The development of light sources emitting at alternative wavelengths, e.g., around #1,060 nm, not only enabled three-dimensional OCT imaging with enhanced choroidal visualization but also improved OCT performance in cataract patients due to reduced scattering losses in this wavelength region. Adaptive optics using deformable mirror technology, with unique high stroke to correct higher-order ocular aberrations, with specially designed optics to compensate chromatic aberration of the human eye, in

  14. Retinal Image Quality During Accommodation

    PubMed Central

    López-Gil, N.; Martin, J.; Liu, T.; Bradley, A.; Díaz-Muñoz, D.; Thibos, L.

    2013-01-01

    Purpose We asked if retinal image quality is maximum during accommodation, or sub-optimal due to accommodative error, when subjects perform an acuity task. Methods Subjects viewed a monochromatic (552nm), high-contrast letter target placed at various viewing distances. Wavefront aberrations of the accommodating eye were measured near the endpoint of an acuity staircase paradigm. Refractive state, defined as the optimum target vergence for maximising retinal image quality, was computed by through-focus wavefront analysis to find the power of the virtual correcting lens that maximizes visual Strehl ratio. Results Despite changes in ocular aberrations and pupil size during binocular viewing, retinal image quality and visual acuity typically remain high for all target vergences. When accommodative errors lead to sub-optimal retinal image quality, acuity and measured image quality both decline. However, the effect of accommodation errors of on visual acuity are mitigated by pupillary constriction associated with accommodation and binocular convergence and also to binocular summation of dissimilar retinal image blur. Under monocular viewing conditions some subjects displayed significant accommodative lag that reduced visual performance, an effect that was exacerbated by pharmacological dilation of the pupil. Conclusions Spurious measurement of accommodative error can be avoided when the image quality metric used to determine refractive state is compatible with the focusing criteria used by the visual system to control accommodation. Real focusing errors of the accommodating eye do not necessarily produce a reliably measurable loss of image quality or clinically significant loss of visual performance, probably because of increased depth-of-focus due to pupil constriction. When retinal image quality is close to maximum achievable (given the eye’s higher-order aberrations), acuity is also near maximum. A combination of accommodative lag, reduced image quality, and reduced

  15. Retinitis pigmentosa in southern Africa.

    PubMed

    Greenberg, J; Bartmann, L; Ramesar, R; Beighton, P

    1993-11-01

    Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal disorders which are a common cause of genetic blindness. The relative frequencies of the different forms of RP in South Africa, as determined from the register at the DNA banking centre for RP at the Department of Human Genetics, University of Cape Town, are presented and discussed. Of the 125 families analysed, 29 (23%) showed autosomal dominant, 33 (27%) autosomal recessive and 3 (3%) X-linked inheritance. In 10 families the pedigree data were insufficient to allow accurate genetic subtyping and a further 50 patients were sporadic without a family history of RP or other syndromic features which would allow categorization.

  16. [Central nervous system relapse with multiple brain masses in an acute promyelocytic leukemia patient treated with all-trans retinoic acid].

    PubMed

    Maeda, A; Kobayashi, Y; Saito, T; Togitani, K; Kawahigashi, N; Tanosaki, R; Takaue, Y; Takenaka, T; Iwata, N; Tobinai, K

    1999-10-01

    A 22-year-old woman with fever and bleeding tendency was given a diagnosis of acute promyelocytic leukemia (APL) on the basis of laboratory findings including a WBC count of 106 x 10(3)/microliter (90% blasts) and a platelet count of 1.6 x 10(4)/microliter. Induction therapy was started with all-trans retinoic acid (ATRA) and cytotoxic chemotherapy. After the patient achieved complete remission, ATRA was discontinued and consolidation chemotherapy was started. However, 4 months after onset, leukemic blasts were detected in cerebrospinal fluid. Temporal central nervous system remission was induced by intrathecal chemotherapy only. However, 2 months later, multiple focal mass lesions had developed in the brain. ATRA (45 mg/m2) was restarted together with multiple intrathecal injections of anticancer drugs, and a third remission was achieved. It is conceivable that the incorporation of ATRA in induction chemotherapy is related to the development of this rather rare complication of APL. The outcome in this case suggested orally administered ATRA may be effective in treating brain metastasis of APL.

  17. Massive myeloid sarcoma affecting the central nervous system, mediastinum, retroperitoneum, liver, and rectum associated with acute myeloblastic leukaemia: a case report

    PubMed Central

    Best-Aguilera, C R; Vazquez-Del Mercado, M; Muñoz-Valle, J F; Herrera-Zarate, L; Navarro-Hernandez, R E; Martin-Marquez, B T; Oregon-Romero, E; Ruiz-Quezada, S; Bonilla, G M; Lomeli-Guerrero, A

    2005-01-01

    Myeloid sarcomas are extramedullary tumours with granulocytic precursors. When associated with acute myelogenous leukaemia (AML), these tumours usually affect no more than two different extramedullary regions. This report describes a myeloid sarcoma associated with AML with tumour formation at five anatomical sites. The patient was a 37 year old man admitted in September 1999 with a two month history of weight loss, symptoms of anaemia, rectal bleeding, and left facial nerve palsy. The anatomical sites affected were: the rectum, the right lobe of the liver, the mediastinum, the retroperitoneum, and the central nervous system. A bone marrow smear was compatible with AML M2. Flow cytometry showed that the peripheral blood was positive for CD4, CD11, CD13, CD14, CD33, CD45, and HLA-DR. A karyotypic study of the bone marrow revealed an 8;21 translocation. The presence of multiple solid tumours in AML is a rare event. Enhanced expression of cell adhesion molecules may be the reason why some patients develop myeloid sarcomas. PMID:15735171

  18. Metronidazole and hydroxymetronidazole central nervous system distribution: 1. microdialysis assessment of brain extracellular fluid concentrations in patients with acute brain injury.

    PubMed

    Frasca, Denis; Dahyot-Fizelier, Claire; Adier, Christophe; Mimoz, Olivier; Debaene, Bertrand; Couet, William; Marchand, Sandrine

    2014-01-01

    The distribution of metronidazole in the central nervous system has only been described based on cerebrospinal fluid data. However, extracellular fluid (ECF) concentrations may better predict its antimicrobial effect and/or side effects. We sought to explore by microdialysis brain ECF metronidazole distribution in patients with acute brain injury. Four brain-injured patients monitored by cerebral microdialysis received 500 mg of metronidazole over 0.5 h every 8 h. Brain dialysates and blood samples were collected at steady state over 8 h. Probe recoveries were evaluated by in vivo retrodialysis in each patient for metronidazole. Metronidazole and OH-metronidazole were assayed by high-pressure liquid chromatography, and a noncompartmental pharmacokinetic analysis was performed. Probe recovery was equal to 78.8% ± 1.3% for metronidazole in patients. Unbound brain metronidazole concentration-time curves were delayed compared to unbound plasma concentration-time curves but with a mean metronidazole unbound brain/plasma AUC0-τ ratio equal to 102% ± 19% (ranging from 87 to 124%). The unbound plasma concentration-time profiles for OH-metronidazole were flat, with mean average steady-state concentrations equal to 4.0 ± 0.7 μg ml(-1). This microdialysis study describes the steady-state brain distribution of metronidazole in patients and confirms its extensive distribution.

  19. High frequency of central memory regulatory T cells allows detection of liver recipients at risk of early acute rejection within the first month after transplantation.

    PubMed

    Boix-Giner, Francisco; Millan, Olga; San Segundo, David; Muñoz-Cacho, Pedro; Mancebo, Esther; Llorente, Santiago; Rafael-Valdivia, Lourdes; Rimola, Antoni; Fábrega, Emilio; Mrowiec, Anna; Allende, Luis; Minguela, Alfredo; Bolarín, Jose M; Paz-Artal, Estela; López-Hoyos, Marcos; Brunet, Mercé; Muro, Manuel

    2016-02-01

    Several studies have analyzed the potential of T regulatory cells (Treg cells) as biomarkers of acute rejection (AR). The aim of the present multicenter study was to correlate the percentage of peripheral Treg cells in liver graft recipients drawn at baseline up to 12 months after transplantation with the presence of AR. The percentage of central memory (cm) Treg cells (CD4(+)CD25(high)CD45RO(+)CD62L(+)) was monitored at pre-transplant and at 1 and 2 weeks, and 1, 2, 3 and 6 months and 1 year post-transplantation. The same validation standard operating procedures were used in all participating centers. Fifteen patients developed AR (23.4%). Hepatitis C virus recurrence was observed in 16 recipients, who displayed low peripheral blood cmTreg levels compared with patients who did not. A steady increase of cmTregs was observed during the first month after transplantation with statistically significant differences between AR and non-AR patients. The high frequency of memory Treg cells allowed us to monitor rejection episodes during the first month post-transplantation. On the basis of these data, we developed a prediction model for assessing risk of AR that can provide clinicians with useful information for managing patients individually and customizing immunosuppressive therapies.

  20. High frequency of central memory regulatory T cells allows detection of liver recipients at risk of early acute rejection within the first month after transplantation

    PubMed Central

    Boix-Giner, Francisco; Millan, Olga; San Segundo, David; Muñoz-Cacho, Pedro; Mancebo, Esther; Llorente, Santiago; Rafael-Valdivia, Lourdes; Rimola, Antoni; Fábrega, Emilio; Mrowiec, Anna; Allende, Luis; Minguela, Alfredo; Bolarín, Jose M.; Paz-Artal, Estela; López-Hoyos, Marcos; Brunet, Mercé

    2016-01-01

    Several studies have analyzed the potential of T regulatory cells (Treg cells) as biomarkers of acute rejection (AR). The aim of the present multicenter study was to correlate the percentage of peripheral Treg cells in liver graft recipients drawn at baseline up to 12 months after transplantation with the presence of AR. The percentage of central memory (cm) Treg cells (CD4+CD25highCD45RO+CD62L+) was monitored at pre-transplant and at 1 and 2 weeks, and 1, 2, 3 and 6 months and 1 year post-transplantation. The same validation standard operating procedures were used in all participating centers. Fifteen patients developed AR (23.4%). Hepatitis C virus recurrence was observed in 16 recipients, who displayed low peripheral blood cmTreg levels compared with patients who did not. A steady increase of cmTregs was observed during the first month after transplantation with statistically significant differences between AR and non-AR patients. The high frequency of memory Treg cells allowed us to monitor rejection episodes during the first month post-transplantation. On the basis of these data, we developed a prediction model for assessing risk of AR that can provide clinicians with useful information for managing patients individually and customizing immunosuppressive therapies. PMID:26270267

  1. An animal model to study toxicity of central nervous system therapy for childhood acute lymphoblastic leukemia: Effects on growth and craniofacial proportion

    SciTech Connect

    Schunior, A.; Zengel, A.E.; Mullenix, P.J.; Tarbell, N.J.; Howes, A.; Tassinari, M.S. )

    1990-10-15

    Many long term survivors of childhood acute lymphoblastic leukemia have short stature, as well as craniofacial and dental abnormalities, as side effects of central nervous system prophylactic therapy. An animal model is presented to assess these adverse effects on growth. Cranial irradiation (1000 cGy) with and without prednisolone (18 mg/kg i.p.) and methotrexate (2 mg/kg i.p.) was administered to 17- and 18-day-old Sprague-Dawley male and female rats. Animals were weighed 3 times/week. Final body weight and body length were measured at 150 days of age. Femur length and craniofacial dimensions were measured directly from the bones, using calipers. For all exposed groups there was a permanent suppression of weight gain with no catch-up growth or normal adolescent growth spurt. Body length was reduced for all treated groups, as were the ratios of body weight to body length and cranial length to body length. Animals subjected to cranial irradiation exhibited microcephaly, whereas those who received a combination of radiation and chemotherapy demonstrated altered craniofacial proportions in addition to microcephaly. Changes in growth patterns and skeletal proportions exhibited sexually dimorphic characteristics. The results indicate that cranial irradiation is a major factor in the growth failure in exposed rats, but chemotherapeutic agents contribute significantly to the outcome of growth and craniofacial dimensions.

  2. New cellular markers at diagnosis are associated with isolated central nervous system relapse in paediatric B-cell precursor acute lymphoblastic leukaemia.

    PubMed

    van der Velden, Vincent H J; de Launaij, Daphne; de Vries, Jeltje F; de Haas, Valerie; Sonneveld, Edwin; Voerman, Jane S A; de Bie, Maaike; Revesz, Tamas; Avigad, Smadar; Yeoh, Allen E J; Swagemakers, Sigrid M A; Eckert, Cornelia; Pieters, Rob; van Dongen, Jacques J M

    2016-03-01

    In childhood acute lymphoblastic leukaemia (ALL), central nervous system (CNS) involvement is rare at diagnosis (1-4%), but more frequent at relapse (~30%). Because of the significant late sequelae of CNS treatment, early identification of patients at risk of CNS relapse is crucial. Using microarray-analysis, we discovered multiple differentially expressed genes between B-cell precursor (BCP) ALL cells in bone marrow (BM) and BCP-ALL cells in cerebrospinal fluid (CSF) at the time of isolated CNS relapse. After confirmation by real-time quantitative polymerase chain reaction, selected genes (including SCD and SPP1) were validated at the protein level by flowcytometric analysis of BCP-ALL cells in CSF. Further flowcytometric validation showed that a subpopulation of BCP-ALL cells (>1%) with a 'CNS protein profile' (SCD positivity and increased SPP1 expression) was present in the BM at diagnosis in patients who later developed an isolated CNS relapse, whereas this subpopulation was <1% or absent in all other patients. These data indicate that the presence of a (small) subpopulation of BCP-ALL cells with a 'CNS protein profile' at diagnosis (particularly SCD-positivity) is associated with isolated CNS relapse. Such information can be used to design new diagnostic and treatment strategies that aim at prevention of CNS relapse with reduced toxicity.

  3. Prevalence and risk factors of cataract after chemotherapy with or without central nervous system irradiation for childhood acute lymphoblastic leukaemia: an LEA study.

    PubMed

    Alloin, Anne-Lise; Barlogis, Vincent; Auquier, Pascal; Contet, Audrey; Poiree, Maryline; Demeocq, François; Herrmann, Iris; Villes, Virginie; Bertrand, Yves; Plantaz, Dominique; Kanold, Justyna; Chastagner, Pascal; Chambost, Hervé; Sirvent, Nicolas; Michel, Gérard

    2014-01-01

    Corticosteroid and central nervous system (CNS) irradiation can induce cataract in childhood lymphoblastic leukaemia survivors. Few prospective studies with systematic ophthalmological evaluation have been published. Cataract was prospectively assessed by serial slip lamp tests in 517 patients. All had acute lymphoblastic leukaemia, all had been treated by chemotherapy with or without CNS irradiation, and none had received haematopoietic stem cell transplantation. Median ages at last evaluation and follow-up duration from leukaemia diagnosis were 16·8 and 10·9 years, respectively. Cataract was observed in 21/517 patients (4·1%). Cumulative incidence was 4·5 ± 1·2% at 15 years and reached 26 ± 8·1% at 25 years. CNS irradiation was the only risk factor: prevalence was 11·1% in patients who had received irradiation and 2·8% in those who did not. We did not detect any steroid dose effect: cumulative dose was 5133 and 5190 mg/m(2) in patients with and without cataract, respectively. Cataract occurrence did not significantly impact quality of life. We conclude that, in the range of steroid dose reported here, the cataract risk proves very low 15 years after treatment without CNS irradiation but an even more prolonged follow-up is required because of potential very late occurrence.

  4. Effects of Acute Confinement Stress-induced Hypothalamic-Pituitary Adrenal Axis Activation and Concomitant Peripheral and Central Transforming Growth Factor-β1 Measures in Nonhuman Primates

    PubMed Central

    Coplan, Jeremy D.; Gopinath, Srinath; Abdallah, Chadi G.; Margolis, Jeffrey; Chen, Wei; Scharf, Bruce A.; Rosenblum, Leonard A.; Batuman, Olcay A.; Smith, Eric L. P.

    2017-01-01

    Transforming growth factor-β1 (TGF-β1) is a multifunctional cytokine with anti-inflammatory, immunosuppressive and neuroprotective properties. The hypothalamic-pituitary-adrenal (HPA) axis and immune system exert bidirectional influences on each other, via cortisol and TGF-β1, but the exact nature of the interaction is not well characterized. The current study examined the effects, in bonnet macaques (Macaca radiata), of two consecutive acute confinement stress periods in an unfamiliar room while mildly restrained, first without and then with dexamethasone pretreatment (0.01 mg/kg IM). Preceding the confinement studies, a non-stress control condition obtained contemporaneous levels of cortisol and TGF-β1 in both plasma and cerebrospinal fluid (CSF) to match the confinement stress studies. Subjects were reared under either normative or variable foraging demand (VFD) conditions. Since there were no rearing effects at baseline or for any of the conditions tested -- either for cortisol or TGF-β -- the study analyses were conducted on the combined rearing groups. The stress condition increased both plasma and CSF cortisol levels whereas dexamethasone pretreatment decreased cortisol concentrations to below baseline levels despite stress. The stress condition decreased TGF-β1 concentrations only in CSF but not in serum. Together the data suggested that stress-induced reductions of a centrally active neuroprotective cytokine occurs in the face of HPA axis activation, potentially facilitating glucocortoid-induced neurotoxicity. Stress-induced reductions of neuroprotective cytokines prompts exploration of protective measures against glucocorticoid-induced neurotoxicity.

  5. Preservation of retinal structure and function after cilioretinal artery occlusion: a case report

    PubMed Central

    Brown, Craig J

    2016-01-01

    Cilioretinal artery occlusion is a cause of sudden, often catastrophic loss of central vision. There are no established effective treatments. Recently, a patient presented 24 hours after a cilioretinal artery occlusion, following a cardiac catheterization prior to which her blood thinners had been discontinued. Lacking an effective way to address the severe retinal ischemic oxidative stress, she was offered, under compassionate use, a multivitamin complex designed to address retinal ischemia and oxidative stress. Significant components of this product are L-methylfolate and n-acetyl cysteine. The patient experienced a rapid unexpected improvement in vision and preservation of retinal structure, suggesting that marked improvement in retinal artery occlusions outcomes may be possible as late as 24 hours postocclusion. This is the third reported case of cilioretinal artery occlusion associated with cardiac catheterization. PMID:26929671

  6. [Retinal vascular changes--predictive and prognostic factor in systemic disease].

    PubMed

    Vicol, Anca Delia; Bogdănici, Tudor; Bogdănici, Camelia

    2014-01-01

    The retinal circulation represents a unique window for the direct, non invazive in vivo status of the systemic mycrocirculation, but it can also offer scientific support for theories related strictly to ocular diseases, such as glaucoma (vascular theory). The interaction between intraocular pressure, retinal vessels and cerebrospinal fluid pressure located at the retrolaminar part of the optic nerve has been of great interest for both ophthalmologists or neuroscientists, both clinicians and researchers. The retinal vascular bed has structural and functional similarities with other vascular teritories such as Central Nervous System (CNS), kidneys and heart, so as for the ophthalmologist any vascular change in the retina can signalize a systemic disease (diabetes mellitus, stroke, arterial hypertension) that is more or less symptomatic for the patient. The purpose of this meta-analysis was to reviview recent literature data related to the connections between different hemodynamic structures and their impact on the retinal blood flow.

  7. In-vivo confocal scanning laser ophthalmoscopic characterization of retinal pathology in a small-eye-animal model

    NASA Astrophysics Data System (ADS)

    Zwick, Harry; Elliot, Rowe; Schuschereba, Steven T.; Lund, David J.; Stuck, Bruce E.

    1997-05-01

    We have used confocal scanning laser ophthalmoscopy (CSLO) to evaluate acute laser retinal injury in a small eye animal model. THe snake eye is optically unique, combining a high numerical aperture with a clear ocular media and a cornea covered with a hard dry spectacle. These optical qualities allow detailed resolution of photoreceptors, retinal nerve fiber, and retinal capillary blood cells in an intact vertebrate eye. We demonstrated that acute laser exposures capable of damaging the photoreceptor matrix may also alter blood flow at more anterior levels of the retina. Changes in photoreceptor density and orientation were indicated in the early post exposure seconds at high dose acute Argon laser exposures. An increase in photoreceptor reflectivity was observed in surviving photoreceptors and was enhanced with a near IR CSLO imaging source. Q-switched exposure failed to show this enhancement, possibly because of greater subchoroidal involvement associated with acoustic damage processes.

  8. Tuberculous Panophthalmitis with Lymphadenitis and Central Nervous System Tuberculoma

    PubMed Central

    Srichatrapimuk, Sirawat; Wattanatranon, Duangkamon

    2016-01-01

    Tuberculosis (TB) is a serious infectious disease that spreads globally. The ocular manifestations of TB are uncommon and diverse. TB panophthalmitis has been rarely reported. Here, we described a 38-year-old Thai man presenting with panophthalmitis of the right eye. Further investigation showed that he had concurrent TB lymphadenitis and central nervous system (CNS) tuberculoma, as well as HIV infection, with a CD4 cell count of 153 cells/mm3. Despite the initial response to antituberculous agents, the disease had subsequently progressed and enucleation was required. The pathological examination revealed acute suppurative granulomatous panophthalmitis with retinal detachment. Further staining demonstrated acid-fast bacilli in the tissue. Colonies of Mycobacterium tuberculosis were obtained from tissue culture. He was treated with antiretroviral agents for HIV infection and 12 months of antituberculous agents. Clinicians should be aware of the possibility of TB in the differential diagnosis of endophthalmitis and panophthalmitis, especially in regions where TB is endemic. PMID:27051539

  9. Retinal vessels caliber changes after strabismus surgery: results of 6mo follow-up

    PubMed Central

    Li, Ji-Peng; Fu, Jing; Zhou, Jin-Qiong; Wang, Xiao-Zhen; Wang, Wen-Ying; Liu, Ning-Pu

    2016-01-01

    AIM To evaluate the effect of strabismus surgery on retinal vessels calibers with digital color fundus photographs. METHODS Two hundred consecutive strabismus patients underwent surgery, and 118 patients (female/male, 55/63) who finished 6-month follow-up were finally included in this study. Optic disc-centered digital color fundus photographs of both eyes of all patients were taken prior to surgery and 6mo post surgery. The retinal vascular caliber of 116 operated eyes were measured using the computer program IVAN. The operated eyes were divided into 3 groups according to the surgical methods, recession of one muscle, one muscle recession and one muscle folding, one muscle resection and one muscle recession. The effect of number of altered muscles on retinal vessels was analyzed using statistic software SPSS 16.0. RESULTS The mean age was 12.4±8.6y. Averaged central retinal artery equivalent (CRAE) of all patients was 120.31±23.02 µm preoperatively, and 122.87±15.93 µm six months after surgery. Averaged central retinal vein equivalent (CRVE) was 171.11±31.73 µm preoperatively and 175.02±21.00 µm postoperatively. There was no significant difference of averaged CRAE (P=0.22) or CRVE (P=0.19) before and after operation. Averaged arteriole to venule ratio (AVR) was 0.71±0.07 before surgery and 0.70±0.07 after surgery. Comparison of preoperative and postoperative retinal vessels calibers among different surgical groups did not show significant differences. Also, there was no advantage of rectus muscle folding to muscle resection. CONCLUSION Up to 6mo after strabismus surgery, the retinal vascular calibers were not altered. No more than two muscles in one surgery are safe for retinal perfusion. PMID:27672600

  10. Digital tracking and control of retinal images

    NASA Astrophysics Data System (ADS)

    Barrett, Steven F.; Jerath, Maya R.; Rylander, Henry G.; Welch, Ashley J.

    1994-01-01

    Laser-induced retinal lesions are used to treat a variety of eye disorders such as diabetic retinopathy and retinal tears. An instrumentation system has been developed to track a specific lesion coordinate on the retinal surface and provide corrective signals to maintain laser position on the coordinate. High-resolution retinal images are acquired via a CCD camera coupled to a fundus camera and video frame grabber. Optical filtering and histogram modification are used to enhance the retinal vessel network against the lighter retinal background. Six distinct retinal landmarks are tracked on the high contrast image obtained from the frame grabber using 2D blood vessel templates. An overview of the robotic laser system design is followed by implementation and testing of a development system for proof of concept and, finally, specifications for a real-time system are provided.

  11. Retinal Regeneration is Facilitated by the Presence of Surviving Neurons

    PubMed Central

    Sherpa, Tshering; Lankford, Tyler; McGinn, Tim E.; Hunter, Samuel S.; Frey, Ruth A.; Sun, Chi; Ryan, Mariel; Robison, Barrie D.; Stenkamp, Deborah L.

    2014-01-01

    Teleost fish regenerate their retinas after damage, in contrast to mammals. In zebrafish subjected to an extensive ouabain-induced lesion that destroys all neurons and spares Müller glia, functional recovery and restoration of normal optic nerve head (ONH) diameter take place at 100 days post-injury. Subsequently, regenerated retinas overproduce cells in the retinal ganglion cell (RGC) layer, and the ONH becomes enlarged. Here we test the hypothesis that a selective injury, which spares photoreceptors and Müller glia, results in faster functional recovery and fewer long-term histological abnormalities. Following this selective retinal damage, recovery of visual function required 60 days, consistent with this hypothesis. In contrast to extensively damaged retinas, selectively damaged retinas showed fewer histological errors and did not overproduce neurons. Extensively damaged retinas had RGC axons that were delayed in pathfinding to the ONH, and showed misrouted axons within the ONH, suggesting that delayed functional recovery following an extensive lesion is related to defects in RGC axons exiting the eye and/or reaching their central targets. The atoh7, fgf8a, shha, and netrin-1 genes were differentially expressed, and the distribution of Hh protein was disrupted following extensive damage as compared with selective damage. Confirming a role for Shh signaling in supporting rapid regeneration, shhat4+/− zebrafish showed delayed functional recovery following selective damage. We suggest that surviving retinal neurons provide structural/molecular information to regenerating neurons, and that this patterning mechanism regulates factors such as Shh. These factors in turn control neuronal number, retinal lamination, and RGC axon pathfinding during retinal regeneration. PMID:24488694

  12. Tyro3 Modulates Mertk-Associated Retinal Degeneration.

    PubMed

    Vollrath, Douglas; Yasumura, Douglas; Benchorin, Gillie; Matthes, Michael T; Feng, Wei; Nguyen, Natalie M; Sedano, Cecilia D; Calton, Melissa A; LaVail, Matthew M

    2015-12-01

    Inherited photoreceptor degenerations (IPDs) are the most genetically heterogeneous of Mendelian diseases. Many IPDs exhibit substantial phenotypic variability, but the basis is usually unknown. Mutations in MERTK cause recessive IPD phenotypes associated with the RP38 locus. We have identified a murine genetic modifier of Mertk-associated photoreceptor degeneration, the C57BL/6 (B6) allele of which acts as a suppressor. Photoreceptors degenerate rapidly in Mertk-deficient animals homozygous for the 129P2/Ola (129) modifier allele, whereas animals heterozygous for B6 and 129 modifier alleles exhibit an unusual intermixing of degenerating and preserved retinal regions, with females more severely affected than males. Mertk-deficient mice homozygous for the B6 modifier allele display degeneration only in the far periphery, even at 8 months of age, and have improved retinal function compared to animals homozygous for the 129 allele. We genetically mapped the modifier to an approximately 2-megabase critical interval that includes Tyro3, a paralog of Mertk. Tyro3 expression in the outer retina varies with modifier genotype in a manner characteristic of a cis-acting expression quantitative trait locus (eQTL), with the B6 allele conferring an approximately three-fold higher expression level. Loss of Tyro3 function accelerates the pace of photoreceptor degeneration in Mertk knockout mice, and TYRO3 protein is more abundant in the retinal pigment epithelium (RPE) adjacent to preserved central retinal regions of Mertk knockout mice homozygous for the B6 modifier allele. Endogenous human TYRO3 protein co-localizes with nascent photoreceptor outer segment (POS) phagosomes in a primary RPE cell culture assay, and expression of murine Tyro3 in cultured cells stimulates phagocytic ingestion of POS. Our findings demonstrate that Tyro3 gene dosage modulates Mertk-associated retinal degeneration, provide strong evidence for a direct role for TYRO3 in RPE phagocytosis, and suggest

  13. Cannabinoids modulate spontaneous synaptic activity in retinal ganglion cells.

    PubMed

    Middleton, T P; Protti, D A

    2011-09-01

    The endocannabinoid (ECB) system has been found throughout the central nervous system and modulates cell excitability in various forms of short-term plasticity. ECBs and their receptors have also been localized to all retinal cells, and cannabinoid receptor activation has been shown to alter voltage-dependent conductances in several different retinal cell types, suggesting a possible role for cannabinoids in retinal processing. Their effects on synaptic transmission in the mammalian retina, however, have not been previously investigated. Here, we show that exogenous cannabinoids alter spontaneous synaptic transmission onto retinal ganglion cells (RGCs). Using whole-cell voltage-clamp recordings in whole-mount retinas, we measured spontaneous postsynaptic currents (SPSCs) in RGCs in adult and young (P14-P21) mice. We found that the addition of an exogenous cannabinoid agonist, WIN55212-2 (5 μM), caused a significant reversible reduction in the frequency of SPSCs. This change, however, did not alter the kinetics of the SPSCs, indicating a presynaptic locus of action. Using blockers to isolate inhibitory or excitatory currents, we found that cannabinoids significantly reduced the release probability of both GABA and glutamate, respectively. While the addition of cannabinoids reduced the frequency of both GABAergic and glutamatergic SPSCs in both young and adult mice, we found that the largest effect was on GABA-mediated currents in young mice. These results suggest that the ECB system may potentially be involved in the modulation of signal transmission in the retina. Furthermore, they suggest that it might play a role in the developmental maturation of synaptic circuits, and that exogenous cannabinoids are likely able to disrupt retinal processing and consequently alter vision.

  14. Retinal Remodeling and Metabolic Alterations in Human AMD

    PubMed Central

    Jones, Bryan W.; Pfeiffer, Rebecca L.; Ferrell, William D.; Watt, Carl B.; Tucker, James; Marc, Robert E.

    2016-01-01

    Age-related macular degeneration (AMD) is a progressive retinal degeneration resulting in central visual field loss, ultimately causing debilitating blindness. AMD affects 18% of Americans from 65 to 74, 30% older than 74 years of age and is the leading cause of severe vision loss and blindness in Western populations. While many genetic and environmental risk factors are known for AMD, we currently know less about the mechanisms mediating disease progression. The pathways and mechanisms through which genetic and non-genetic risk factors modulate development of AMD pathogenesis remain largely unexplored. Moreover, current treatment for AMD is palliative and limited to wet/exudative forms. Retina is a complex, heterocellular tissue and most retinal cell classes are impacted or altered in AMD. Defining disease and stage-specific cytoarchitectural and metabolic responses in AMD is critical for highlighting targets for intervention. The goal of this article is to illustrate cell types impacted in AMD and demonstrate the implications of those changes, likely beginning in the retinal pigment epithelium (RPE), for remodeling of the the neural retina. Tracking heterocellular responses in disease progression is best achieved with computational molecular phenotyping (CMP), a tool that enables acquisition of a small molecule fingerprint for every cell in the retina. CMP uncovered critical cellular and molecular pathologies (remodeling and reprogramming) in progressive retinal degenerations such as retinitis pigmentosa (RP). We now applied these approaches to normal human and AMD tissues mapping progression of cellular and molecular changes in AMD retinas, including late-stage forms of the disease. PMID:27199657

  15. Non-contact ultra-widefield retinal imaging of infants with suspected abusive head trauma.

    PubMed

    Yusuf, I H; Barnes, J K; Fung, T H M; Elston, J S; Patel, C K

    2017-03-01

    PurposeThe purpose of the study was to audit the use of non-contact ultra-widefield retinal imaging in infants with suspected abusive head trauma (AHT) using the Optos P200MA Scanning Laser Ophthalmoscope.Patients and methodsA retrospective, observational case series. Ten eyes of five consecutive infants (aged 1-15 months) with suspected (or in 1 case, known) AHT referred for an ophthalmological opinion were included. Each infant underwent non-contact ultra-widefield retinal imaging using the Optos P200MA scanning laser ophthalmoscope. Optos fundus fluorescein angiography (FFA) was performed in one infant with oral sedation. The other four infants did not require sedation. The main outcome measure was the acquisition of a single, definitive ultra-widefield retinal image in each eye. Safety was audited by determining adverse changes in heart rate and oxygen saturations that required cessation of imaging.ResultsThe Optos P200MA ultra-widefield scanning laser ophthalmoscope acquired good quality retinal images in all infants. Documentation of acute, widespread retinal haemorrhages contributed to a diagnosis of AHT in three infants. Chronic pre-macular haemorrhage and macular schisis were documented by FFA in a fourth infant. The absence of retinal haemorrhages was documented in a fifth infant contributing to the exclusion of a diagnosis of AHT. There were no adverse safety signals in any infant in this series.ConclusionThe Optos P200MA ultra-widefield scanning laser ophthalmoscope appears safe to use in infants with suspected AHT, providing high-quality retinal images in a single frame without ocular contact. Optos P200MA may be used as alternative to RetCam to document retinal haemorrhages in stable infants with suspected AHT.

  16. Automatic temperature controlled retinal photocoagulation

    NASA Astrophysics Data System (ADS)

    Schlott, Kerstin; Koinzer, Stefan; Ptaszynski, Lars; Bever, Marco; Baade, Alex; Roider, Johann; Birngruber, Reginald; Brinkmann, Ralf

    2012-06-01

    Laser coagulation is a treatment method for many retinal diseases. Due to variations in fundus pigmentation and light scattering inside the eye globe, different lesion strengths are often achieved. The aim of this work is to realize an automatic feedback algorithm to generate desired lesion strengths by controlling the retinal temperature increase with the irradiation time. Optoacoustics afford non-invasive retinal temperature monitoring during laser treatment. A 75 ns/523 nm Q-switched Nd:YLF laser was used to excite the temperature-dependent pressure amplitudes, which were detected at the cornea by an ultrasonic transducer embedded in a contact lens. A 532 nm continuous wave Nd:YAG laser served for photocoagulation. The ED50 temperatures, for which the probability of ophthalmoscopically visible lesions after one hour in vivo in rabbits was 50%, varied from 63°C for 20 ms to 49°C for 400 ms. Arrhenius parameters were extracted as ΔE=273 J mol-1 and A=3.1044 s-1. Control algorithms for mild and strong lesions were developed, which led to average lesion diameters of 162+/-34 μm and 189+/-34 μm, respectively. It could be demonstrated that the sizes of the automatically controlled lesions were widely independent of the treatment laser power and the retinal pigmentation.

  17. Retinitis Pigmentosa and Education Issues

    ERIC Educational Resources Information Center

    Brown, Thomas J.

    2005-01-01

    Retinitis Pigmentosa includes a number of inherited diseases which usually result in blindness. The disease is progressive in nature and begins with the deterioration of cells in the eye responsible for peripheral vision. As the condition worsens there is a gradual loss of peripheral vision and night blindness. Proper educational planning requires…

  18. Automatic temperature controlled retinal photocoagulation.

    PubMed

    Schlott, Kerstin; Koinzer, Stefan; Ptaszynski, Lars; Bever, Marco; Baade, Alex; Roider, Johann; Birngruber, Reginald; Brinkmann, Ralf

    2012-06-01

    Laser coagulation is a treatment method for many retinal diseases. Due to variations in fundus pigmentation and light scattering inside the eye globe, different lesion strengths are often achieved. The aim of this work is to realize an automatic feedback algorithm to generate desired lesion strengths by controlling the retinal temperature increase with the irradiation time. Optoacoustics afford non-invasive retinal temperature monitoring during laser treatment. A 75 ns/523 nm Q-switched Nd:YLF laser was used to excite the temperature-dependent pressure amplitudes, which were detected at the cornea by an ultrasonic transducer embedded in a contact lens. A 532 nm continuous wave Nd:YAG laser served for photocoagulation. The ED50 temperatures, for which the probability of ophthalmoscopically visible lesions after one hour in vivo in rabbits was 50%, varied from 63°C for 20 ms to 49°C for 400 ms. Arrhenius parameters were extracted as ΔE=273 J mol(-1) and A=3 x 10(44) s(-1). Control algorithms for mild and strong lesions were developed, which led to average lesion diameters of 162 ± 34 μm and 189 ± 34 μm, respectively. It could be demonstrated that the sizes of the automatically controlled lesions were widely independent of the treatment laser power and the retinal pigmentation.

  19. TULP1 Mutations Causing Early-Onset Retinal Degeneration: Preserved but Insensitive Macular Cones

    PubMed Central

    Jacobson, Samuel G.; Cideciyan, Artur V.; Huang, Wei Chieh; Sumaroka, Alexander; Roman, Alejandro J.; Schwartz, Sharon B.; Luo, Xunda; Sheplock, Rebecca; Dauber, Joanna M.; Swider, Malgorzata; Stone, Edwin M.

    2014-01-01

    Purpose. To investigate visual function and outer and inner retinal structure in the rare form of retinal degeneration (RD) caused by TULP1 (tubby-like protein 1) mutations. Methods. Retinal degeneration patients with TULP1 mutations (n = 5; age range, 5–36 years) were studied by kinetic and chromatic static perimetry, en face autofluorescence imaging, and spectral-domain optical coherence tomography (OCT) scans. Outer and inner retinal laminar thickness were measured and mapped across the central retina. Comparisons were made with results from patients with RD associated with four ciliopathy genotypes (MAK, RPGR, BBS1, and USH2A). Results. The TULP1-RD patients were severely affected already in the first decade of life and there was rapidly progressive visual loss. No evidence of rod function was present at any age. Small central islands showed melanized retinal pigment epithelium by autofluorescence imaging and well-preserved photoreceptor laminar thickness by OCT imaging. There was extracentral loss of laminar architecture and increased inner retinal thickening. Structure-function relationships in residual foveal cone islands were made in TULP1-RD patients and in other retinopathies considered ciliopathies. Patients with TULP1-RD, unlike the others, had greater dysfunction for the degree of foveal structural preservation. Conclusions. Retinal degeneration with TULP1 mutations leads to a small central island of residual foveal cones at early ages. These cones are less sensitive than expected from the residual structure. The human phenotype is consistent with experimental evidence in the Tulp1 knockout mouse model that visual dysfunction could be complicated by abnormal processes proximal to cone outer segments. PMID:25074776

  20. Retinal detachment in a patient with extensive myelinated retinal nerve fibers.

    PubMed

    Chen, Muh-Shy; Ho, Tzyy-Chang; Chang, Ching-Chung; Hou, Ping-Kang

    2007-01-01

    We report extensive myelinated retinal nerve fibers in a 42-year-old patient with retinal detachment. Fundus examination revealed a horseshoe-shaped tear near the temporal edge. Pars plana vitrectomy was performed and firm vitreo-retinal adhesion was noticed in the area of extensive myelinated retinal nerve fibers. Following vitrectomy with silicone oil tamponade, the retina was reattached successfully. In conclusion, retinal detachment may develop in patients with extensive myelinated retinal nerve fibers. Vitrectomy may be performed to treat this condition.

  1. Comparison of Common Retinal Vessel Caliber Measurement Software and a Conversion Algorithm

    PubMed Central

    Yip, WanFen; Tham, Yih Chung; Hsu, Wynne; Lee, Mong Li; Klein, Ronald; Klein, Barbara; Ikram, Mohammad Kamran; Wong, Tien Yin; Cheung, Carol Yim-lui

    2016-01-01

    Purpose To compare three commonly used retinal vessel caliber measurement software systems, and propose an algorithm for conversion between measurement systems. Methods We used 120 retinal photographs to evaluate the agreement between three commonly used software (Retinal Analysis [RA], Integrative Vessel Analysis [IVAN], and Singapore I Vessel Assessment [SIVA]). Bland-Altman plots were used to evaluate agreement of retinal arteriolar (central retinal artery equivalent, CRAE) and venular (central retinal vein equivalent, CRVE) calibers. Pearson's correlation was used to assess the associations between systemic factors and retinal vessel calibers, and Z-test was used to compare the strength of the correlation coefficients across the three software systems. An algorithm was created to convert measurements, with paired t-test performed to evaluate the differences between SIVA-measured retinal calibers and SIVA-approximates converted from RA- and IVAN-measurements using the algorithm. Results Differences between SIVA- and RA-measured calibers (CRAE: mean difference [MD] = −21.8 μm, 95% limits of agreement [LOA], −47.3 to 3.7 μm; CRVE: MD = −7.7 μm, 95% LOA, −28.0 to 12.6 μm), SIVA- and IVAN-measured calibers (CRAE: MD = −6.7 μm, 95% LOA, −23.8 to 10.4 μm; CRVE: MD = −18.2 μm 95% LOA, −36.7 to 0.4 μm) were large. However, the strength of correlations between systemic factors with SIVA-measured retinal calibers was not significantly different to that measured using RA and IVAN (P ≥ 0.332). SIVA-approximates converted from RA and IVAN measurements using the proposed algorithm was not significantly different from SIVA-measured calibers (P ≥ 0.20). Conclusion Absolute measurements of retinal vessel calibers vary between three common software systems but associations with systemic factors were similar. Translational Relevance The proposed algorithm allowed conversions of RA and IVAN measurements to SIVA-approximates. This conversion is important

  2. Two-Step Reactivation of Dormant Cones in Retinitis Pigmentosa

    PubMed Central

    Wang, Wei; Lee, Sang Joon; Scott, Patrick A.; Lu, Xiaoqin; Emery, Douglas; Liu, Yongqin; Ezashi, Toshihiko; Roberts, Michael R.; Ross, Jason W.; Kaplan, Henry J.; Dean, Douglas C.

    2016-01-01

    Most Retinitis Pigmentosa (RP) mutations arise in rod photoreceptor genes, leading to diminished peripheral and nightime vision. Using a pig model of autosomal-dominant RP, we show glucose becomes sequestered in the retinal pigment epithelium (RPE), and thus is not transported to photoreceptors. The resulting starvation for glucose metabolites impairs synthesis of cone visual pigment -rich outer segments (OS), and then their mitochondrial-rich inner segments dissociate. Loss of these functional structures diminishes cone-dependent high-resolution central vision, which is utilized for most daily tasks. By transplanting wild-type rods, to restore glucose transport, or directly replacing glucose in the subretinal space, to bypass its retention in the RPE, we can regenerate cone functional structures, reactivating the dormant cells. Beyond providing metabolic building blocks for cone functional structures, we show glucose induces thioredoxin-interacting protein (Txnip) to regulate Akt signaling, thereby shunting metabolites toward aerobic glucose metabolism and regenerating cone OS synthesis. PMID:27050517

  3. Vaccination for protection of retinal ganglion cells against death from glutamate cytotoxicity and ocular hypertension: Implications for glaucoma

    NASA Astrophysics Data System (ADS)

    Schori, Hadas; Kipnis, Jonathan; Yoles, Eti; Woldemussie, Elizabeth; Ruiz, Guadalupe; Wheeler, Larry A.; Schwartz, Michal

    2001-03-01

    Our group recently demonstrated that autoimmune T cells directed against central nervous system-associated myelin antigens protect neurons from secondary degeneration. We further showed that the synthetic peptide copolymer 1 (Cop-1), known to suppress experimental autoimmune encephalomyelitis, can be safely substituted for the natural myelin antigen in both passive and active immunization for neuroprotection of the injured optic nerve. Here we attempted to determine whether similar immunizations are protective from retinal ganglion cell loss resulting from a direct biochemical insult caused, for example, by glutamate (a major mediator of degeneration in acute and chronic optic nerve insults) and in a rat model of ocular hypertension. Passive immunization with T cells reactive to myelin basic protein or active immunization with myelin oligodendrocyte glycoprotein-derived peptide, although neuroprotective after optic nerve injury, was ineffective against glutamate toxicity in mice and rats. In contrast, the number of surviving retinal ganglion cells per square millimeter in glutamate-injected retinas was significantly larger in mice immunized 10 days previously with Cop-1 emulsified in complete Freund's adjuvant than in mice injected with PBS in the same adjuvant (2,133 ± 270 and 1,329 ± 121, respectively, mean ± SEM; P < 0.02). A similar pattern was observed when mice were immunized on the day of glutamate injection (1,777 ± 101 compared with 1,414 ± 36; P <0.05), but not when they were immunized 48h later. These findings suggest that protection from glutamate toxicity requires reinforcement of the immune system by antigens that are different from those associated with myelin. The use of Cop-1 apparently circumvents this antigen specificity barrier. In the rat ocular hypertension model, which simulates glaucoma, immunization with Cop-1 significantly reduced the retinal ganglion cell loss from 27.8%±6.8% to 4.3%±1.6%, without affecting the intraocular pressure

  4. Impact of Cranial Irradiation Added to Intrathecal Conditioning in Hematopoietic Cell Transplantation in Adult Acute Myeloid Leukemia With Central Nervous System Involvement

    SciTech Connect

    Mayadev, Jyoti S.; Douglas, James G.; Storer, Barry E.; Appelbaum, Frederick R.; Storb, Rainer

    2011-05-01

    Purpose: Neither the prognostic importance nor the appropriate management of central nervous system (CNS) involvement is known for patients with acute myeloid leukemia (AML) undergoing hematopoietic cell transplantation (HCT). We examined the impact of a CNS irradiation boost to standard intrathecal chemotherapy (ITC). Methods and Materials: From 1995 to 2005, a total of 648 adult AML patients received a myeloablative HCT: 577 patients were CNS negative (CNS-), and 71 were CNS positive (CNS+). Of the 71 CNS+ patients, 52 received intrathecal chemotherapy alone (CNS+ITC), and 19 received ITC plus an irradiation boost (CNS+RT). Results: The CNS-, CNS+ITC, and CNS+RT patients had 1- and 5-year relapse-free survivals (RFS) of 43% and 35%, 15% and 6%, and 37% and 32%, respectively. CNS+ITC patients had a statistically significant worse RFS compared with CNS- patients (hazard ratio [HR], 2.65; 95% confidence interval [CI], 2.0-3.6; p < 0.0001). CNS+RT patients had improved relapse free survival over that of CNS+ITC patients (HR, 0.45; 95% CI, 0.2-0.8; p = 0.01). The 1- and 5-year overall survivals (OS) of patients with CNS-, CNS+ITC, and CNS+RT, were 50% and 38%, 21% and 6%, and 53% and 42%, respectively. The survival of CNS+RT were significantly better than CNS+ITC patients (p = 0.004). After adjusting for known risk factors, CNS+RT patients had a trend toward lower relapse rates and reduced nonrelapse mortality. Conclusions: CNS+ AML is associated with a poor prognosis. The role of a cranial irradiation boost to intrathecal chemotherapy appears to mitigate the risk of CNS disease, and needs to be further investigated to define optimal treatment strategies.

  5. Central nervous system involvement in adult acute lymphoblastic leukemia at diagnosis: results from the international ALL trial MRC UKALL XII/ECOG E2993

    PubMed Central

    Lazarus, Hillard M.; Richards, Susan M.; Chopra, Raj; Litzow, Mark R.; Burnett, Alan K.; Wiernik, Peter H.; Franklin, Ian M.; Tallman, Martin S.; Cook, Lucy; Buck, Georgina; Durrant, I. Jill; Rowe, Jacob M.; Goldstone, Anthony H.

    2006-01-01

    Outcome of acute lymphoblastic leukemia (ALL) in adults with central nervous system (CNS) disease at diagnosis is unclear. We treated 1508 de novo ALL patients with 2-phase induction and then high-dose methotrexate with l-asparaginase. Patients up to 50 years old in first remission (CR1) with a matched related donor (MRD) underwent an allogeneic stem cell transplantation (SCT); the remainder in CR1 were randomized to an autologous SCT or intensive consolidation followed by maintenance chemotherapy. Philadelphia chromosome (Ph)–positive patients were offered a matched unrelated donor (MUD) allogeneic SCT. Seventy-seven of 1508 (5%) patients a median age of 29 years had CNS leukemia at presentation; 13 of the 77 (17%) had Ph-positive ALL. Sixty-nine of 77 (90%) patients attained CR1. Thirty-six patients underwent transplantation in CR1 (25 MRD, 5 MUD, and 6 autografts). Eleven of 25 patients with MRD transplantation remain alive at 21 to 102 months, 2 of 5 with MUD at 42 and 71 months, and 1 of 6 with autologous SCT at 35 months. Seven of 27 treated with consolidation/maintenance remain in CR1 56 to 137 months after diagnosis. Overall survival at 5 years was 29% in those with CNS involvement at diagnosis versus 38% (P = .03) for those without. CNS leukemia in adult ALL is uncommon at diagnosis. Adult Ph-negative ALL patients, however, can attain long-term disease-free survival using SCT as well as conventional chemotherapy. PMID:16556888

  6. Retinal vasculature classification using novel multifractal features

    NASA Astrophysics Data System (ADS)

    Ding, Y.; Ward, W. O. C.; Duan, Jinming; Auer, D. P.; Gowland, Penny; Bai, L.

    2015-11-01

    Retinal blood vessels have been implicated in a large number of diseases including diabetic retinopathy and cardiovascular diseases, which cause damages to retinal blood vessels. The availability of retinal vessel imaging provides an excellent opportunity for monitoring and diagnosis of retinal diseases, and automatic analysis of retinal vessels will help with the processes. However, state of the art vascular analysis methods such as counting the number of branches or measuring the curvature and diameter of individual vessels are unsuitable for the microvasculature. There has been published research using fractal analysis to calculate fractal dimensions of retinal blood vessels, but so far there has been no systematic research extracting discriminant features from retinal vessels for classifications. This paper introduces new methods for feature extraction from multifractal spectra of retinal vessels for classification. Two publicly available retinal vascular image databases are used for the experiments, and the proposed methods have produced accuracies of 85.5% and 77% for classification of healthy and diabetic retinal vasculatures. Experiments show that classification with multiple fractal features produces better rates compared with methods using a single fractal dimension value. In addition to this, experiments also show that classification accuracy can be affected by the accuracy of vessel segmentation algorithms.

  7. Pharmacologic vitreolysis with ocriplasmin: rationale for use and therapeutic potential in vitreo-retinal disorders.

    PubMed

    Khoshnevis, Matin; Sebag, J

    2015-04-01

    With increased knowledge about the origins and pathophysiology of vitreo-retinal disorders—and, in particular, the central role of anomalous posterior vitreous detachment in vitreo-maculopathies—a paradigm shift from surgery to pharmacotherapy is taking place with the development of pharmacologic vitreolysis. The first approved agent for pharmacologic vitreolysis therapy is ocriplasmin, a truncated form of the nonspecific serine protease plasmin. Twelve studies comprise the current ocriplasmin clinical trial program, demonstrating the efficacy and safety of a single intravitreal injection of ocriplasmin for the treatment of patients with symptomatic vitreo-macular adhesion or vitreo-macular traction, including patients with macular holes. Although post-approval implementation of ocriplamsin in clinical practice has shown success rates of up to 78%, there have been recent case reports of acute, transient visual dysfunction. There are thus new initiatives to further refine clinical indications for case selection and to identify possible untoward effects. Although more studies are warranted, it appears that ocriplasmin offers a good alternative to surgery. The future lies in pharmacologic vitreolysis, and the future of pharmacologic vitreolysis lies in prevention. Thus, long-term studies are needed to define a role for pharmacologic vitreolysis, in particular with ocriplasmin, in the prevention of progressive diabetic retinopathy and age-related macular degeneration.

  8. [Vitreo-retinal surgery for complicated retinal detachment].

    PubMed

    Wang, J Z

    1993-07-01

    93 eyes (93 patients) of complicated retinal detachment were treated with vitreo-retinal surgery. Among the series, 75 eyes were rhegmatogenous with PVR C3-D3 in 66 eyes (88.0%), while the remaining 18 eyes were traction induced. None of the cases had giant tears or complicating diabetes. On discharge from the hospital, the operation was effective in 62 cases (66.7%), in whom the retina was totally reattached or only a small amount of subretinal fluid remained. In a group of 40 eyes where the inert gas SF6 was used, the operation was effective in 30 cases (75.0%). 41 cases were followed up postoperatively for over 3 months, averaging 13.7 months, to find the operative results stable in 33 eyes (80.5%), with the visual acuity improved in 22 cases (66.7%), unchanged in 9 cases (27.3%), and decreased in 2 cases (6.0%). The operative procedures, the peeling of pre-retinal membrane, the effect of PVR severity on the operative results, and the promotion of operative efficacy by application of wide encircling buckle and inert gas tamponade were discussed.

  9. Long-term Outcomes in Ranibizumab-Treated Patients With Retinal Vein Occlusion; The Role of Progression of Retinal Nonperfusion

    PubMed Central

    Sophie, Raafay; Hafiz, Gulnar; Scott, Adrienne W.; Zimmer-galler, Ingrid; Dong Nguyen, Quan; Ying, Howard; Do, Diana V.; Solomon, Sharon; Sodhi, Akrit; Gehlbach, Peter; Duh, Elia; Baranano, David; Campochiaro, Peter A.

    2014-01-01

    PURPOSE To determine the percentage of ranibizumab-treated patients with retinal vein occlusion (RVO) who had resolution of edema for at least 6 months after the last injection, along with factors and outcomes that correlate with resolution. DESIGN Post hoc analysis of open-label clinical trial. METHODS Twenty patients with branch RVO (BRVO) and 20 with central RVO (CRVO) received ranibizumab monthly for 3 months and as needed for recurrent/persistent macular edema, no more frequently than every 2 months. Patients still requiring injections after month 40 received scatter and grid laser photocoagulation to try to reduce the need for injections. Main outcome measures included the percentage of patients who had resolution of edema, change in best-corrected visual acuity (BCVA) from baseline, and change in area of retinal nonperfusion in central subfields. RESULTS Nine patients with BRVO (45%) had edema resolution from injections alone after a mean of 20.2 months, 4 resolved after addition of laser, 4 were unresolved through 72 months, and 3 exited prior to resolution. Five patients with CRVO (25%) resolved from injections alone after a mean of 14.0 months, 8 remained unresolved through 72 months despite addition of laser, and 7 exited prior to resolution. For BRVO or CRVO, there was a negative correlation between posterior retinal nonperfusion area and BCVA at months 18, 24, and 36 (P < .05). CONCLUSIONS In patients with RVO, infrequent ranibizumab injections to control edema may not be sufficient to prevent progression of retinal nonperfusion, which may contribute to loss of visual gains. PMID:24053892

  10. Retinal and post-retinal contributions to the quantum efficiency of the human eye revealed by electrical neuroimaging.

    PubMed

    Manasseh, Gibran; de Balthasar, Chloe; Sanguinetti, Bruno; Pomarico, Enrico; Gisin, Nicolas; de Peralta, Rolando Grave; Andino, Sara L Gonzalez

    2013-01-01

    The retina is one of the best known quantum detectors with rods able to reliably respond to single photons. However, estimates on the number of photons eliciting conscious perception, based on signal detection theory, are systematically above these values after discounting by retinal losses. One possibility is that there is a trade-off between the limited motor resources available to living systems and the excellent reliability of the visual photoreceptors. On this view, the limits to sensory thresholds are not set by the individual reliability of the receptors within each sensory modality (as often assumed) but rather by the limited central processing and motor resources available to process the constant inflow of sensory information. To investigate this issue, we reproduced the classical experiment from Hetch aimed to determine the sensory threshold in human vision. We combined a careful physical control of the stimulus parameters with high temporal/spatial resolution recordings of EEG signals and behavioral variables over a relatively large sample of subjects (12). Contrarily to the idea that the limits to visual sensitivity are fully set by the statistical fluctuations in photon absorption on retinal photoreceptors we observed that the state of ongoing neural oscillations before any photon impinges the retina helps to determine if the responses of photoreceptors have access to central conscious processing. Our results suggest that motivational and attentional off-retinal mechanisms play a major role in reducing the QE efficiency of the human visual system when compared to the efficiency of isolated retinal photoreceptors. Yet, this mechanism might subserve adaptive behavior by enhancing the overall multisensory efficiency of the whole system composed by diverse reliable sensory modalities.

  11. Retinal and post-retinal contributions to the quantum efficiency of the human eye revealed by electrical neuroimaging

    PubMed Central

    Manasseh, Gibran; de Balthasar, Chloe; Sanguinetti, Bruno; Pomarico, Enrico; Gisin, Nicolas; de Peralta, Rolando Grave; Andino, Sara L. Gonzalez

    2013-01-01

    The retina is one of the best known quantum detectors with rods able to reliably respond to single photons. However, estimates on the number of photons eliciting conscious perception, based on signal detection theory, are systematically above these values after discounting by retinal losses. One possibility is that there is a trade-off between the limited motor resources available to living systems and the excellent reliability of the visual photoreceptors. On this view, the limits to sensory thresholds are not set by the individual reliability of the receptors within each sensory modality (as often assumed) but rather by the limited central processing and motor resources available to process the constant inflow of sensory information. To investigate this issue, we reproduced the classical experiment from Hetch aimed to determine the sensory threshold in human vision. We combined a careful physical control of the stimulus parameters with high temporal/spatial resolution recordings of EEG signals and behavioral variables over a relatively large sample of subjects (12). Contrarily to the idea that the limits to visual sensitivity are fully set by the statistical fluctuations in photon absorption on retinal photoreceptors we observed that the state of ongoing neural oscillations before any photon impinges the retina helps to determine if the responses of photoreceptors have access to central conscious processing. Our results suggest that motivational and attentional off-retinal mechanisms play a major role in reducing the QE efficiency of the human visual system when compared to the efficiency of isolated retinal photoreceptors. Yet, this mechanism might subserve adaptive behavior by enhancing the overall multisensory efficiency of the whole system composed by diverse reliable sensory modalities. PMID:24302913

  12. cGMP-Phosphodiesterase Inhibition Prevents Hypoxia-Induced Cell Death Activation in Porcine Retinal Explants.

    PubMed

    Olivares-González, Lorena; Martínez-Fernández de la Cámara, Cristina; Hervás, David; Marín, María Pilar; Lahoz, Agustin; Millán, José María; Rodrigo, Regina

    2016-01-01

    Retinal hypoxia and oxidative stress are involved in several retinal degenerations including diabetic retinopathy, glaucoma, central retinal artery occlusion, or retinopathy of prematurity. The second messenger cyclic guanosine monophosphate (cGMP) has been reported to be protective for neuronal cells under several pathological conditions including ischemia/hypoxia. The purpose of this study was to evaluate whether the accumulation of cGMP through the pharmacological inhibition of phosphodiesterase (PDE) with Zaprinast prevented retinal degeneration induced by mild hypoxia in cultures of porcine retina. Exposure to mild hypoxia (5% O2) for 24h reduced cGMP content and induced retinal degeneration by caspase dependent and independent (PARP activation) mechanisms. Hypoxia also produced a redox imbalance reducing antioxidant response (superoxide dismutase and catalase activities) and increasing superoxide free radical release. Zaprinast reduced mild hypoxia-induced cell death through inhibition of caspase-3 or PARP activation depending on the cell layer. PDE inhibition also ameliorated the effects of mild hypoxia on antioxidant response and the release of superoxide radical in the photoreceptor layer. The use of a PKG inhibitor, KT5823, suggested that cGMP-PKG pathway is involved in cell survival and antioxidant response. The inhibition of PDE, therefore, could be useful for reducing retinal degeneration under hypoxic/ischemic conditions.

  13. cGMP-Phosphodiesterase Inhibition Prevents Hypoxia-Induced Cell Death Activation in Porcine Retinal Explants

    PubMed Central

    Olivares-González, Lorena; Martínez-Fernández de la Cámara, Cristina; Hervás, David; Marín, María Pilar; Lahoz, Agustin; Millán, José María

    2016-01-01

    Retinal hypoxia and oxidative stress are involved in several retinal degenerations including diabetic retinopathy, glaucoma, central retinal artery occlusion, or retinopathy of prematurity. The second messenger cyclic guanosine monophosphate (cGMP) has been reported to be protective for neuronal cells under several pathological conditions including ischemia/hypoxia. The purpose of this study was to evaluate whether the accumulation of cGMP through the pharmacological inhibition of phosphodiesterase (PDE) with Zaprinast prevented retinal degeneration induced by mild hypoxia in cultures of porcine retina. Exposure to mild hypoxia (5% O2) for 24h reduced cGMP content and induced retinal degeneration by caspase dependent and independent (PARP activation) mechanisms. Hypoxia also produced a redox imbalance reducing antioxidant response (superoxide dismutase and catalase activities) and increasing superoxide free radical release. Zaprinast reduced mild hypoxia-induced cell death through inhibition of caspase-3 or PARP activation depending on the cell layer. PDE inhibition also ameliorated the effects of mild hypoxia on antioxidant response and the release of superoxide radical in the photoreceptor layer. The use of a PKG inhibitor, KT5823, suggested that cGMP-PKG pathway is involved in cell survival and antioxidant response. The inhibition of PDE, therefore, could be useful for reducing retinal degeneration under hypoxic/ischemic conditions. PMID:27861632

  14. Changes in ganglion cell physiology during retinal degeneration influence excitability by prosthetic electrodes

    NASA Astrophysics Data System (ADS)

    Cho, Alice; Ratliff, Charles; Sampath, Alapakkam; Weiland, James

    2016-04-01

    Objective. Here we investigate ganglion cell physiology in healthy and degenerating retina to test its influence on threshold to electrical stimulation. Approach. Age-related Macular Degeneration and Retinitis Pigmentosa cause blindness via outer retinal degeneration. Inner retinal pathways that transmit visual information to the central brain remain intact, so direct electrical stimulation from prosthetic devices offers the possibility for visual restoration. Since inner retinal physiology changes during degeneration, we characterize physiological properties and responses to electrical stimulation in retinal ganglion cells (RGCs) of both wild type mice and the rd10 mouse model of retinal degeneration. Main results. Our aggregate results support previous observations that elevated thresholds characterize diseased retinas. However, a physiology-driven classification scheme reveals distinct sub-populations of ganglion cells with thresholds either normal or strongly elevated compared to wild-type. When these populations are combined, only a weakly elevated threshold with large variance is observed. The cells with normal threshold are more depolarized at rest and exhibit periodic oscillations. Significance. During degeneration, physiological changes in RGCs affect the threshold stimulation currents required to evoke action potentials.

  15. Retinal blood vessels extraction using probabilistic modelling.

    PubMed

    Kaba, Djibril; Wang, Chuang; Li, Yongmin; Salazar-Gonzalez, Ana; Liu, Xiaohui; Serag, Ahmed

    2014-01-01

    The analysis of retinal blood vessels plays an important role in detecting and treating retinal diseases. In this review, we present an automated method to segment blood vessels of fundus retinal image. The proposed method could be used to support a non-intrusive diagnosis in modern ophthalmology for early detection of retinal diseases, treatment evaluation or clinical study. This study combines the bias correction and an adaptive histogram equalisation to enhance the appearance of the blood vessels. Then the blood vessels are extracted using probabilistic modelling that is optimised by the expectation maximisation algorithm. The method is evaluated on fundus retinal images of STARE and DRIVE datasets. The experimental results are compared with some recently published methods of retinal blood vessels segmentation. The experimental results show that our method achieved the best overall performance and it is comparable to the performance of human experts.

  16. Mitochondria mediates caspase-dependent and independent retinal cell death in Staphylococcus aureus endophthalmitis

    PubMed Central

    Singh, P K; Kumar, A

    2016-01-01

    Bacterial endophthalmitis, a vision-threatening complication of ocular surgery or trauma, is characterized by increased intraocular inflammation and retinal tissue damage. Although significant vision loss in endophthalmitis has been linked to retinal cell death, the underlying mechanisms of cell death remain elusive. In this study, using a mouse model of Staphylococcus aureus endophthalmitis and cultured human retinal Müller glia (MIO-M1 cell line), we demonstrate that S. aureus caused significant apoptotic cell death in the mouse retina and Müller glia, as evidenced by increased number of terminal dUTP nick end labeling and Annexin V and propidium iodide-positive cells. Immunohistochemistry and western blot studies revealed the reduction in mitochondrial membrane potential (JC-1 staining), release of cytochrome c into the cytosol, translocation of Bax to the mitochondria and the activation of caspase-9 and -3 in S. aureus-infected retina/retinal cells. In addition, the activation of PARP-1 and the release of apoptosis inducing factor from mitochondria was also observed in S. aureus-infected retinal cells. Inhibition studies using pan-caspase (Q-VD-OPH) and PARP-1 (DPQ) inhibitors showed significant reduction in S. aureus-induced retinal cell death both in vivo and in vitro. Together, our findings demonstrate that in bacterial endophthalmitis, retinal cells undergo apoptosis in the both caspase-dependent and independent manners, and mitochondria have a central role in this process. Hence, targeting the identified signaling pathways may provide the rationale to design therapeutic interventions to prevent bystander retinal tissue damage in bacterial endophthalmitis. PMID:27551524

  17. Retinal Toxicity in Patients Treated With Hydroxychloroquine: A Cross-Sectional Study.

    PubMed

    Espandar, Goldis; Moghimi, Jamileh; Ghorbani, Raheb; Pourazizi, Mohsen; Seiri, Mohammad-Ali; Khosravi, Shervin

    2016-01-01

    Hydroxychloroquine (HCQ) is an antimalarial medication that can also be used to treat autoimmune diseases. However, it can produce irreversible changes to the retina that lead to visual impairment. The aim of this study was to determine the proportion of patients treated with HCQ who develop retinal toxicity and the risk factors for the development of HCQ-induced retinal toxicity among Iranian patients. The is a cross-sectional clinical study of 59 patients who were treated with HCQ during 2014-2015. A questionnaire was used to collect data on the following demographic and clinical factors: age, gender, type of rheumatic disease, history of cataract surgery, daily and cumulative HCQ dose, and duration of HCQ use. Retinal toxicity was diagnosed on the basis of the automated perimetry results of the central 10° of vision and spectral domain optical coherence tomography. The associations between the demographic and clinical factors and retinal toxicity were assessed, and P < 0.05 was considered statistically significant. Retinal toxicity was detected in 18 (30.5%) of the patients, and 5 (8.5 %) developed color vision impairments. There was no association between retinal toxicity and sex (P = 0.514), history of cataract surgery (P = 0.479), type of rheumatic disease (P = 0.539), or daily HCQ dose (P = 0.062). However, there was a significant positive association between retinal toxicity and age (P = 0.006), cumulative HCQ dose (P = 0.002), and duration of HCQ use (P < 0.001). In conclusion, the risk factors for retinal toxicity after HCQ treatment were advanced age, use of a higher cumulative HCQ dose, and a longer duration of treatment.

  18. Retinal Toxicity in Patients Treated With Hydroxychloroquine: A Cross-Sectional Study

    PubMed Central

    ESPANDAR, Goldis; MOGHIMI, Jamileh; GHORBANI, Raheb; POURAZIZI, Mohsen; SEIRI, Mohammad-Ali; KHOSRAVI, Shervin

    2016-01-01

    Hydroxychloroquine (HCQ) is an antimalarial medication that can also be used to treat autoimmune diseases. However, it can produce irreversible changes to the retina that lead to visual impairment. The aim of this study was to determine the proportion of patients treated with HCQ who develop retinal toxicity and the risk factors for the development of HCQ-induced retinal toxicity among Iranian patients. The is a cross-sectional clinical study of 59 patients who were treated with HCQ during 2014–2015. A questionnaire was used to collect data on the following demographic and clinical factors: age, gender, type of rheumatic disease, history of cataract surgery, daily and cumulative HCQ dose, and duration of HCQ use. Retinal toxicity was diagnosed on the basis of the automated perimetry results of the central 10° of vision and spectral domain optical coherence tomography. The associations between the demographic and clinical factors and retinal toxicity were assessed, and P < 0.05 was considered statistically significant. Retinal toxicity was detected in 18 (30.5%) of the patients, and 5 (8.5 %) developed color vision impairments. There was no association between retinal toxicity and sex (P = 0.514), history of cataract surgery (P = 0.479), type of rheumatic disease (P = 0.539), or daily HCQ dose (P = 0.062). However, there was a significant positive association between retinal toxicity and age (P = 0.006), cumulative HCQ dose (P = 0.002), and duration of HCQ use (P < 0.001). In conclusion, the risk factors for retinal toxicity after HCQ treatment were advanced age, use of a higher cumulative HCQ dose, and a longer duration of treatment. PMID:28293646

  19. Retinal complications after bungee jumping.

    PubMed

    Filipe, J A; Pinto, A M; Rosas, V; Castro-Correia, J

    Bungee jumping is becoming a popular sport in the Western world with some cases of ophthalmic complications being reported in recent literature. The authors reported a case of a 23-year-old healthy female who presented retinal complications following a bungee jumping. Her fundi showed superficial retinal hemorrhages in the right eye and a sub-internal limiting membrane hemorrhage affecting the left eye. A general examination, including a full neurological examination, was normal and laboratorial investigations were all within normal values. More studies are necessary to identify risk factors and the true incidence of related ocular lesions, but until then, we think this sport activity should be desencouraged, especially to those that are not psychological and physically fit.

  20. Mechanical Dissociation of Retinal Neurons with Vibration

    NASA Astrophysics Data System (ADS)

    Motomura, Tamami; Hayashida, Yuki; Murayama, Nobuki

    The neuromorphic device, which implements the functions of biological neural circuits by means of VLSI technology, has been collecting much attention in the engineering fields in the last decade. Concurrently, progress in neuroscience research has revealed the nonlinear computation in single neuron levels, suggesting that individual neurons are not merely the circuit elements but computational units. Thus, elucidating the properties of neuronal signal processing is thought to be an essential step for developing the next generation of neuromorphic devices. In the present study, we developed a method for dissociating single neurons from specific sublayers of mammalian retinas with using no proteolytic enzymes but rather combining tissue incubation in a low-Ca2+ medium and the vibro-dissociation technique developed for the slices of brains and spinal cords previously. Our method took shorter time of the procedure, and required less elaborated skill, than the conventional enzymatic method did; nevertheless it yielded enough number of the cells available for acute electrophysiological experiments. The isolated retinal neurons were useful for measuring the nonlinear membrane conductances as well as the spike firing properties under the perforated-patch whole-cell configuration. These neurons also enabled us to examine the effects of proteolytic enzymes on the membrane excitability in those cells.

  1. [Retinal ischemia and nitric oxide].

    PubMed

    Neroev, V V; Arkhipova, M M

    2003-01-01

    Retinal ischemia is the main chain in the pathogenesis of vascular diseases of the eye. It was established that nitric oxide (NO) plays the key role in the development of ischemia. Recent understanding of the NO role, as a universal regulator of the cellular and tissue metabolism, is presented. The authors' and published data were used to design a scheme of pathogenesis of retinal ischemia with regard for the NO role. NO can produce both positive and negative effects depending on a stage of the process, NO concentration and on a number of other factors if they are present. Initial stages of hypoxia/ischemia are accompanied by an activation of all forms of NO-synthases (NOS) caused by the influence of biologically active substances (cytokines, prostaglandins, serotonin, bradykinin, glycolisis suboxide products etc.). The activation of inducible NOS, which synthesize a bigger quantity of NO possessing a direct cytotoxic action and contributing to the production of highly toxic radical of peroxinitrit, is in the focus of attention. The damage of cellular structures due to free-radical processes leads to the development of endothelial, macrophage and thrombocyte malfunctions, which manifest itself through a reduced activity of endothelial NOS and through disruption of NO-dependent processes (vasospasm, an increased aggregation of platelets and a reduced fibrinolytic activity). A sharp reduction of NO synthesis substrate (L-arginine) is observed in patients with retinal ischemia. The aggravation of ischemia causes a decrease of NO synthesis due to an exhaustion of L-arginine and its intensified consumption in the course of free-radical processes. The use of NO-inhibitors and of NO-donors at different stages of retinal ischemia prevents the development of neovascularization and proliferation.

  2. Microelectronic Array for Stimulation of Retinal Tissue

    DTIC Science & Technology

    2005-01-01

    from diseases such as retinitis pigmentosa and age-related macular degeneration are the leading causes of blindness in the developing world...53featured research 2005 NRL Review Microelectronic Array for Stimulation of Retinal Tissue D. Scribner,1 L. Johnson,4 P. Skeath,4 R. Klein,4...GOALS The development of a high-resolution retinal prosthesis device at the Naval Research Laboratory (NRL) was first discussed in the late 1990s

  3. Inherited Retinal Degenerative Clinical Trial Network. Addendum

    DTIC Science & Technology

    2013-10-01

    visual impairment usually ending in blindness. In the United States, the total number of individuals affected by retinitis pigmentosa (RP) and other...linica l trial in the NEER network for autosomal dominant retinitis pigmentosa , and the ProgSTAR studies for Stargardt disease) . As new interventions b... retinitis pigmentosa continues at six sites- the CTEC site at University of Utah and five additional recruitment sites- the Retina Foundation of the

  4. Retinal Morphology and Sensitivity Are Primarily Impaired in Eyes with Neuromyelitis Optica Spectrum Disorder (NMOSD)

    PubMed Central

    Akiba, Ryutaro; Yokouchi, Hirotaka; Mori, Masahiro; Oshitari, Toshiyuki; Baba, Takayuki; Sawai, Setsu; Kuwabara, Satoshi; Yamamoto, Shuichi

    2016-01-01

    Background Previous studies of neuromyelitis optica spectrum disorder (NMOSD) using spectral domain optical coherence tomography (SD-OCT) showed that the outer nuclear layer (ONL) in eyes without a history of optic neuritis (ON) was thinner than that of healthy controls. It remains unclear whether the ONL thinning is caused by a direct attack on the retina by an autoantibody or a retrograde degeneration. Objective To determine the mechanisms involved in the retinal damage in eyes with NMOSD without ON. Methods SD-OCT was used to determine the thicknesses of the different retinal layers of 21 eyes of 12 NMOSD patients without prior ON and 19 eyes of 10 healthy controls. Eyes with peripapillary retinal nerve fiber layer (RNFL) thinning were excluded to eliminate the confounding effects of retrograde degeneration. Microperimetry was used to determine the central retinal sensitivity. The data of the two groups were compared using generalized estimated equation models to account for inter-eye dependencies. Results The ganglion cell plus inner plexiform layer and the inner nuclear layer plus outer plexiform layer thicknesses of the NMOSD eyes were not significantly different from that of the control eyes (P = 0.28, P = 0.78). However, the ONL and average macular thickness (AMT) in the NMOSD eyes were significantly thinner than that of the control eyes (P = 0.022, P = 0.036). The retinal sensitivity in the central 10°, 10° to 2°, and 2° sectors were significantly lower in the NMOSD eyes than in the control eyes (P = 0.013, P = 0.022, P = 0.002). Conclusions The ONL thinning, AMT thinning, and reduced retinal sensitivity in eyes with NMOSD without significant peripapillary RNFL thinning are most likely due to direct retinal pathology. PMID:27936154

  5. Retinal Macroglial Responses in Health and Disease

    PubMed Central

    de Hoz, Rosa; Rojas, Blanca; Ramírez, Ana I.; Salazar, Juan J.; Gallego, Beatriz I.; Triviño, Alberto; Ramírez, José M.

    2016-01-01

    Due to their permanent and close proximity to neurons, glial cells perform essential tasks for the normal physiology of the retina. Astrocytes and Müller cells (retinal macroglia) provide physical support to neurons and supplement them with several metabolites and growth factors. Macroglia are involved in maintaining the homeostasis of extracellular ions and neurotransmitters, are essential for information processing in neural circuits, participate in retinal glucose metabolism and in removing metabolic waste products, regulate local blood flow, induce the blood-retinal barrier (BRB), play fundamental roles in local immune response, and protect neurons from oxidative damage. In response to polyetiological insults, glia cells react with a process called reactive gliosis, seeking to maintain retinal homeostasis. When malfunctioning, macroglial cells can become primary pathogenic elements. A reactive gliosis has been described in different retinal pathologies, including age-related macular degeneration (AMD), diabetes, glaucoma, retinal detachment, or retinitis pigmentosa. A better understanding of the dual, neuroprotective, or cytotoxic effect of macroglial involvement in retinal pathologies would help in treating the physiopathology of these diseases. The extensive participation of the macroglia in retinal diseases points to these cells as innovative targets for new drug therapies. PMID:27294114

  6. Mitochondrial dysfunction underlying outer retinal diseases.

    PubMed

    Lefevere, Evy; Toft-Kehler, Anne Katrine; Vohra, Rupali; Kolko, Miriam; Moons, Lieve; Van Hove, Inge

    2017-03-29

    Dysfunction of photoreceptors, retinal pigment epithelium (RPE) or both contribute to the initiation and progression of several outer retinal disorders. Disrupted Müller glia function might additionally subsidize to these diseases. Mitochondrial malfunctioning is importantly associated with outer retina pathologies, which can be classified as primary and secondary mitochondrial disorders. This review highlights the importance of oxidative stress and mitochondrial DNA damage, underlying outer retinal disorders. Indeed, the metabolically active photoreceptors/RPE are highly prone to these hallmarks of mitochondrial dysfunction, indicating that mitochondria represent a weak link in the antioxidant defenses of outer retinal cells.

  7. Hypoxia-Induced Retinal Neovascularization in Zebrafish Embryos: A Potential Model of Retinopathy of Prematurity

    PubMed Central

    Kao, Alex; Hsi, Brian; Lee, Shwu-Huey; Chen, Yau-Hung; Wang, I-Jong

    2015-01-01

    Retinopathy of prematurity, formerly known as a retrolental fibroplasia, is a leading cause of infantile blindness worldwide. Retinopathy of prematurity is caused by the failure of central retinal vessels to reach the retinal periphery, creating a nonperfused peripheral retina, resulting in retinal hypoxia, neovascularization, vitreous hemorrhage, vitreoretinal fibrosis, and loss of vision. We established a potential retinopathy of prematurity model by using a green fluorescent vascular endothelium zebrafish transgenic line treated with cobalt chloride (a hypoxia-inducing agent), followed by GS4012 (a vascular endothelial growth factor inducer) at 24 hours postfertilization, and observed that the number of vascular branches and sprouts significantly increased in the central retinal vascular trunks 2–4 days after treatment. We created an angiography method by using tetramethylrhodamine dextran, which exhibited severe vascular leakage through the vessel wall into the surrounding retinal tissues. The quantification of mRNA extracted from the heads of the larvae by using real-time quantitative polymerase chain reaction revealed a twofold increase in vegfaa and vegfr2 expression compared with the control group, indicating increased vascular endothelial growth factor signaling in the hypoxic condition. In addition, we demonstrated that the hypoxic insult could be effectively rescued by several antivascular endothelial growth factor agents such as SU5416, bevacizumab, and ranibizumab. In conclusion, we provide a simple, highly reproducible, and clinically relevant retinopathy of prematurity model based on zebrafish embryos; this model may serve as a useful platform for clarifying the mechanisms of human retinopathy of prematurity and its progression. PMID:25978439

  8. Hypoxia-induced retinal neovascularization in zebrafish embryos: a potential model of retinopathy of prematurity.

    PubMed

    Wu, Yu-Ching; Chang, Chao-Yuan; Kao, Alex; Hsi, Brian; Lee, Shwu-Huey; Chen, Yau-Hung; Wang, I-Jong

    2015-01-01

    Retinopathy of prematurity, formerly known as a retrolental fibroplasia, is a leading cause of infantile blindness worldwide. Retinopathy of prematurity is caused by the failure of central retinal vessels to reach the retinal periphery, creating a nonperfused peripheral retina, resulting in retinal hypoxia, neovascularization, vitreous hemorrhage, vitreoretinal fibrosis, and loss of vision. We established a potential retinopathy of prematurity model by using a green fluorescent vascular endothelium zebrafish transgenic line treated with cobalt chloride (a hypoxia-inducing agent), followed by GS4012 (a vascular endothelial growth factor inducer) at 24 hours postfertilization, and observed that the number of vascular branches and sprouts significantly increased in the central retinal vascular trunks 2-4 days after treatment. We created an angiography method by using tetramethylrhodamine dextran, which exhibited severe vascular leakage through the vessel wall into the surrounding retinal tissues. The quantification of mRNA extracted from the heads of the larvae by using real-time quantitative polymerase chain reaction revealed a twofold increase in vegfaa and vegfr2 expression compared with the control group, indicating increased vascular endothelial growth factor signaling in the hypoxic condition. In addition, we demonstrated that the hypoxic insult could be effectively rescued by several antivascular endothelial growth factor agents such as SU5416, bevacizumab, and ranibizumab. In conclusion, we provide a simple, highly reproducible, and clinically relevant retinopathy of prematurity model based on zebrafish embryos; this model may serve as a useful platform for clarifying the mechanisms of human retinopathy of prematurity and its progression.

  9. Effect of Axial Eye Length on Retinal Vessel Parameters in 6 to 12-Year-Old Malay Girls

    PubMed Central

    Tai, Evelyn Li Min; Li, Ling-Jun; Wan-Hazabbah, Wan Hitam; Wong, Tien-Yin; Shatriah, Ismail

    2017-01-01

    Purpose Retinal vessel analysis is affected by both systemic and ocular factors. Malays are the major ethnicity in South East Asia. Data on the retinal microvasculature in Malays is limited, especially among children. We aim to evaluate the influence of ocular biometry on retinal vessel parameters in young Malay girls. Methods This was a cross-sectional, hospital-based study involving 86 Malay girls aged 6 to 12 years old in Hospital Universiti Sains Malaysia from 2015–2016. Ocular examination, refraction, biometry, retinal photography, and anthropometric measurements were performed. The central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE) and overall fractal dimension (Df) were measured using validated computer-based methods (Singapore I vessel analyzer, SIVA version 3.0, Singapore). The associations of ocular biometry and CRAE, CRVE and Df were analyzed using multivariable analysis. Results The mean CRAE, CRVE and Df in Malay girls were 171.40 (14.40) um, 248.02 (16.95) um and 1.42 (0.05) respectively. Each 1 mm increase in axial length was associated with a reduction of 4.25 um in the CRAE (p = 0.03) and a reduction of 0.02 in the Df (p = 0.02), after adjustment for age, blood pressure and body mass index. No association was observed between axial length and CRVE. Anterior chamber depth and corneal curvature had no association with CRAE, CRVE or Df. Conclusion Axial length affects retinal vessel measurements. Narrower retinal arterioles and reduced retinal fractal dimension were observed in Malay girls with longer axial lengths. PMID:28107389

  10. RP1L1 variants are associated with a spectrum of inherited retinal diseases including retinitis pigmentosa and occult macular dystrophy.

    PubMed

    Davidson, Alice E; Sergouniotis, Panagiotis I; Mackay, Donna S; Wright, Genevieve A; Waseem, Naushin H; Michaelides, Michel; Holder, Graham E; Robson, Anthony G; Moore, Anthony T; Plagnol, Vincent; Webster, Andrew R

    2013-03-01

    In one consanguineous family with retinitis pigmentosa (RP), a condition characterized by progressive visual loss due to retinal degeneration, homozygosity mapping, and candidate gene sequencing suggested a novel locus. Exome sequencing identified a homozygous frameshifting mutation, c.601delG, p.Lys203Argfs*28, in RP1L1 encoding RP 1-like1, a photoreceptor-specific protein. A screen of a further 285 unrelated individuals with autosomal recessive RP identified an additional proband, homozygous for a missense variant, c.1637G>C, p.Ser546Thr, in RP1L1. A distinct retinal disorder, occult macular dystrophy (OCMD) solely affects the central retinal cone photoreceptors and has previously been reported to be associated with variants in the same gene. The association between mutations in RP1L1 and the disorder OCMD was explored by screening a cohort of 28 unrelated individuals with the condition; 10 were found to harbor rare (minor allele frequency ≤0.5% in the 1,000 genomes dataset) heterozygous RP1L1 missense variants. Analysis of family members revealed many unaffected relatives harboring the same variant. Linkage analysis excluded the possibility of a recessive mode of inheritance, and sequencing of RP1, a photoreceptor protein that interacts with RP1L1, excluded a digenic mechanism involving this gene. These findings imply an important and diverse role for RP1L1 in human retinal physiology and disease.

  11. The peptidomimetic Vasotide targets two retinal VEGF receptors and reduces pathological angiogenesis in murine and nonhuman primate models of retinal disease

    PubMed Central

    Sidman, Richard L.; Li, Jianxue; Lawrence, Matthew; Hu, Wenzheng; Musso, Gary F.; Giordano, Ricardo J.; Cardó-Vila, Marina; Pasqualini, Renata; Arap, Wadih

    2016-01-01

    Blood vessel growth from preexisting vessels (angiogenesis) underlies many severe diseases including major blinding retinal diseases such as retinopathy of prematurity (ROP) and aged macular degeneration (AMD). This observation has driven development of antibody inhibitors that block a central factor in AMD, named vascular endothelial growth factor (VEGF), from binding to its receptors VEGFR-1 and VEGFR-2. However, some patients are insensitive to current anti-VEGF drugs or develop resistance, and the required repeated intravitreal injection of these large molecules is costly and clinically problematic. Here, we have evaluated a small cyclic retro-inverted peptidomimetic, D(Cys-Leu-Pro-Arg-Cys), abbreviated as D(CLPRC), and hereafter named Vasotide, that inhibits retinal angiogenesis by binding selectively to the VEGF receptors, VEGFR-1 and Neuropilin-1 (NRP-1). Delivery of Vasotide in eye drops or via intraperitoneal injection in a laser-induced monkey model of human wet AMD, a mouse genetic knockout model of the AMD subtype called retinal angiomatous proliferation (RAP), and a mouse oxygen-induced model of retinopathy of prematurity (ROP) markedly decreased retinal angiogenesis in all three animal models. This prototype drug candidate is a promising new dual receptor inhibitor of the VEGF ligand with potential for translation into safer, less invasive applications to combat pathological angiogenesis in retinal disorders. PMID:26468327

  12. Retinal pigment epithelium transplantation: concepts, challenges, and future prospects

    PubMed Central

    Alexander, P; Thomson, H A J; Luff, A J; Lotery, A J

    2015-01-01

    The retinal pigment epithelium (RPE) is a single layer of cells that supports the light-sensitive photoreceptor cells that are essential for retinal function. Age-related macular degeneration (AMD) is a leading cause of visual impairment, and the primary pathogenic mechanism is thought to arise in the RPE layer. RPE cell structure and function are well understood, the cells are readily sustainable in laboratory culture and, unlike other cell types within the retina, RPE cells do not require synaptic connections to perform their role. These factors, together with the relative ease of outer retinal imaging, make RPE cells an attractive target for cell transplantation compared with other cell types in the retina or central nervous system. Seminal experiments in rats with an inherited RPE dystrophy have demonstrated that RPE transplantation can prevent photoreceptor loss and maintain visual function. This review provides an update on the progress made so far on RPE transplantation in human eyes, outlines potential sources of donor cells, and describes the technical and surgical challenges faced by the transplanting surgeon. Recent advances in the understanding of pluripotent stem cells, combined with novel surgical instrumentation, hold considerable promise, and support the concept of RPE transplantation as a regenerative strategy in AMD. PMID:26043704

  13. Polymerase chain reaction analysis of aqueous humour samples in necrotising retinitis

    PubMed Central

    Tran, T H C; Rozenberg, F; Cassoux, N; Rao, N A; LeHoang, P; Bodaghi, B

    2003-01-01

    Aim: To evaluate the diagnostic value of polymerase chain reaction (PCR) performed on aqueous humour for the detection of viral DNA in patients with necrotising herpetic retinitis. Methods: The clinical features and laboratory results of 22 patients (29 eyes) presenting with necrotising herpetic retinitis between March 1999 and June 2001 were reviewed retrospectively. Aqueous humour was obtained after anterior chamber paracentesis and PCR was performed in all cases. Results: Viral DNA was detected in the aqueous humour of 19 patients (86.4%). Epstein-Barr virus (EBV) seroconversion was evidenced in one additional patient. In the acute retinal necrosis (ARN) group (n = 19), varicella zoster virus (VZV) DNA was identified in six patients, herpes simplex virus 1 (HSV-1) DNA in two patients, herpes simplex virus 2 (HSV-2) DNA in four patients, and cytomegalovirus (CMV) genome in four patients. In the progressive outer retinal necrosis (PORN) group (n = 3), VZV DNA was detected in all patients. No sample was positive for more than one virus. Conclusions: PCR analysis of aqueous humour in patients with clinical features of necrotising viral retinitis can provide specific aetiological orientation and the method appears to be safe and highly sensitive. PMID:12488268

  14. Does retinal configuration make the head and eyes of foveate birds move?

    PubMed

    Moore, Bret A; Tyrrell, Luke P; Pita, Diana; Bininda-Emonds, Olaf R P; Fernández-Juricic, Esteban

    2017-01-12

    Animals move their heads and eyes to compensate for movements of the body and background, search, fixate, and track objects visually. Avian saccadic head/eye movements have been shown to vary considerably between species. We tested the hypothesis that the configuration of the retina (i.e., changes in retinal ganglion cell density from the retinal periphery to the center of acute vision-fovea) would account for the inter-specific variation in avian head/eye movement behavior. We characterized retinal configuration, head movement rate, and degree of eye movement of 29 bird species with a single fovea, controlling for the effects of phylogenetic relatedness. First, we found the avian fovea is off the retinal center towards the dorso-temporal region of the retina. Second, species with a more pronounced rate of change in ganglion cell density across the retina generally showed a higher degree of eye movement and higher head movement rate likely because a smaller retinal area with relatively high visual acuity leads to greater need to move the head/eye to align this area that contains the fovea with objects of interest. Our findings have implications for anti-predator behavior, as many predator-prey interaction models assume that the sensory system of prey (and hence their behavior) varies little between species.

  15. Does retinal configuration make the head and eyes of foveate birds move?

    PubMed Central

    Moore, Bret A.; Tyrrell, Luke P.; Pita, Diana; Bininda-Emonds, Olaf R. P.; Fernández-Juricic, Esteban

    2017-01-01

    Animals move their heads and eyes to compensate for movements of the body and background, search, fixate, and track objects visually. Avian saccadic head/eye movements have been shown to vary considerably between species. We tested the hypothesis that the configuration of the retina (i.e., changes in retinal ganglion cell density from the retinal periphery to the center of acute vision-fovea) would account for the inter-specific variation in avian head/eye movement behavior. We characterized retinal configuration, head movement rate, and degree of eye movement of 29 bird species with a single fovea, controlling for the effects of phylogenetic relatedness. First, we found the avian fovea is off the retinal center towards the dorso-temporal region of the retina. Second, species with a more pronounced rate of change in ganglion cell density across the retina generally showed a higher degree of eye movement and higher head movement rate likely because a smaller retinal area with relatively high visual acuity leads to greater need to move the head/eye to align this area that contains the fovea with objects of interest. Our findings have implications for anti-predator behavior, as many predator-prey interaction models assume that the sensory system of prey (and hence their behavior) varies little between species. PMID:28079062

  16. Herpetic (non-cytomegalovirus) retinal infections in patients with the acquired immunodeficiency syndrome.

    PubMed

    Stewart, Michael W

    2013-04-01

    Human herpes viruses cause significant morbidity in patients with the acquired immunodeficiency syndrome. Even after the introduction of highly active anti-retroviral therapy (HAART), herpes viruses remain the leading causes of blindness in AIDS patients. Cytomegalovirus (CMV) retinitis and the closely-related immune reconstitution uveitis syndrome are the most common causes of blindness, but progressive outer retinal necrosis and acute retinal necrosis due to varicella zoster and herpes simplex are also important causes of vision loss. Successful treatment of these conditions requires an aggressive approach with multi-drug intravenous therapy or repeated intravitreal antiviral injections. Since the rate of retinal detachment is alarmingly high despite successful antiviral therapy, internists and ophthalmologists must work closely together to recognize and treat complications as they arise. Fortunately, Epstein-Barr virus is a rare cause of retinal infection and human herpes virus (HHV)-6, HHV-7, and HHV-8 do not appear to be primary pathogens. However, increasing evidence suggests that HHV-6 and HHV-7 play important roles in modulating the immune system and potentiating infection by CMV.

  17. Defining incidence, risk factors, and impact on survival of central line-associated blood stream infections following hematopoietic cell transplantation in acute myeloid leukemia and myelodysplastic syndrome.

    PubMed

    Lukenbill, Joshua; Rybicki, Lisa; Sekeres, Mikkael A; Zaman, Muhammad Omer; Copelan, Alexander; Haddad, Housam; Fraser, Thomas; DiGiorgio, Megan J; Hanna, Rabi; Duong, Hien; Hill, Brian; Kalaycio, Matt; Sobecks, Ronald; Bolwell, Brian; Copelan, Edward

    2013-05-01

    Central line-associated blood stream infections (CLABSI) commonly complicate the care of patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) after allogeneic stem cell transplantation (HCT). We developed a modified CLABSI (MCLABSI) definition that attempts to exclude pathogens usually acquired because of disruption of mucosal barriers during the vulnerable neutropenic period following HCT that are generally included under the original definition (OCLABSI). We conducted a retrospective study of all AML and MDS patients undergoing HCT between August 2009 and December 2011 at the Cleveland Clinic (N = 73), identifying both OCLABSI and MCLABSI incidence. The median age at transplantation was 52 years (range, 16 to 70); 34 had a high (≥3) HCT comorbidity index (HCT-CI); 34 received bone marrow (BM), 24 received peripheral stem cells (PSC), and 15 received umbilical cord blood cells (UCB). Among these 73 patients, 23 (31.5%) developed OCLABSI, of whom 16 (69.6%) died, and 8 (11%) developed MCLABSI, of whom 7 (87.5%) died. OCLABSI was diagnosed a median of 9 days from HCT: 5 days (range, 2 to 12) for UCB and 78 days (range, 7 to 211) for BM/PSC (P < .001). MCLABSI occurred a median of 12 days from HCT, with similar earlier UCB and later BM/PSC diagnosis (P = .030). Risk factors for OCLABSI in univariate analysis included CBC (P < .001), human leukocyte antigen (HLA)-mismatch (P = .005), low CD34(+) count (P = .007), low total nucleated cell dose (P = .016), and non-Caucasian race (P = .017). Risk factors for OCLABSI in multivariable analysis were UCB (P < .001) and high HCT-CI (P = .002). There was a significant increase in mortality for both OCLABSI (hazard ratio, 7.14; CI, 3.31 to 15.37; P < .001) and MCLABSI (hazard ratio, 6.44; CI, 2.28 to 18.18; P < .001). CLABSI is common and associated with high mortality in AML and MDS patients undergoing HCT, especially in UCB recipients and those with high HCT-CI. We propose

  18. Anti-VEGF Therapy for Retinal Vein Occlusions.

    PubMed

    Campa, Claudio; Alivernini, Giuseppe; Bolletta, Elena; Parodi, Maurizio Battaglia; Perri, Paolo

    2016-01-01

    Retinal vein occlusion (RVO) is the second most common cause of visual loss in the Western World. RVO is usually classified into branch RVO (BRVO) and central RVO (CRVO) according to the anatomical site of the vascular occlusion. The pathogenesis of RVO is not yet fully understood, however an important event is the intraluminal thrombus formation, which is usually secondary to several conditions such as hypertension, hyperlipidemia, diabetes and thrombophilia. The blockage of venous circulation causes an elevation of intraluminal pressure in the capillaries, leading to hemorrhages and leakage of fluid within the retina, increase of interstitial pressure and a consequent reduction of retinal perfusion. Ischemia may develop resulting in secretion of vascular endothelial growth factor (VEGF) that causes further vascular leakage and retinal oedema. VEGF has therefore a leading role in RVO pathogenesis and symptoms. As a consequence use of anti-VEGF agents by intravitreal injections has become very common with the aim to improve the clinical outcomes in these patients. Currently 2 anti-VEGF agents (ranimizumab and aflibercept) have been FDA (Food and Drug Administration) and EMA (European Medicine Agency) approved for the treatment of RVO, while another VEGF inhibitor (bevacizumab) is often used "off-label" in clinical practice. Many treatment regimens have been suggested in the clinical trials with these drugs, as monthly injections or injections when needed, however the ideal regimen has not been defined yet. We conducted a systematic review searching MEDLINE for the following terms: retinal vein occlusion, ranibizumab, bevacizumab, aflibercept, vascular endothelial growth factor, macular oedema. Data were extracted by one author (AG and BE) and checked by a second (BPM, CC). Aim of this article was to review available data for each drug, focusing on their efficacy and safety trying to compare their advantages and limits.

  19. Optical properties of retinal tissue and the potential of adaptive optics to visualize retinal ganglion cells in vivo.

    PubMed

    Prasse, Martina; Rauscher, Franziska Georgia; Wiedemann, Peter; Reichenbach, Andreas; Francke, Mike

    2013-08-01

    Many efforts have been made to improve the diagnostic tools used to identify and to estimate the progress of ganglion cell and nerve fibre degeneration in glaucoma. Imaging by optical coherence tomography and measurements of the dimensions of the optic nerve head and the nerve fibre layer in central retinal areas is currently used to estimate the grade of pathological changes. The visualization and quantification of ganglion cells and nerve fibres directly in patients would dramatically improve glaucoma diagnostics. We have investigated the optical properties of cellular structures of retinal tissue in order to establish a means of visualizing and quantifying ganglion cells in the living retina without staining. We have characterized the optical properties of retinal tissue in several species including humans. Nerve fibres, blood vessels, ganglion cells and their cell processes have been visualized at high image resolution by means of the reflection mode of a confocal laser scanning microscope. The potential of adaptive optics in current imaging systems and the possibilities of imaging single ganglion cells non-invasively in patients are discussed.

  20. Caffeine administration prevents retinal neuroinflammation and loss of retinal ganglion cells in an animal model of glaucoma

    PubMed Central

    Madeira, Maria H.; Ortin-Martinez, Arturo; Nadal-Nícolas, Francisco; Ambrósio, António F.; Vidal-Sanz, Manuel; Agudo-Barriuso, Marta; Santiago, Ana Raquel

    2016-01-01

    Glaucoma is the second leading cause of blindness worldwide, being characterized by progressive optic nerve damage and loss of retinal ganglion cells (RGCs), accompanied by increased inflammatory response involving retinal microglial cells. The etiology of glaucoma is still unknown, and despite elevated intraocular pressure (IOP) being a major risk factor, the exact mechanisms responsible for RGC degeneration remain unknown. Caffeine, which is an antagonist of adenosine receptors, is the most widely consumed psychoactive drug in the world. Several evidences suggest that caffeine can attenuate the neuroinflammatory responses and afford protection upon central nervous system (CNS) injury. We took advantage of a well characterized animal model of glaucoma to investigate whether caffeine administration controls neuroinflammation and elicits neuroprotection. Caffeine or water were administered ad libitum and ocular hypertension (OHT) was induced by laser photocoagulation of the limbal veins in Sprague Dawley rats. Herein, we show that caffeine is able to partially decrease the IOP in ocular hypertensive animals. More importantly, we found that drinking caffeine prevented retinal microglia-mediated neuroinflammatory response and attenuated the loss of RGCs in animals with ocular hypertension (OHT). This study opens the possibility that caffeine or adenosine receptor antagonists might be a therapeutic option to manage RGC loss in glaucoma. PMID:27270337

  1. Retinal fundus imaging in mouse models of retinal diseases.

    PubMed

    Alex, Anne F; Heiduschka, Peter; Eter, Nicole

    2013-01-01

    The development of in vivo retinal fundus imaging in mice has opened a new research horizon, not only in ophthalmic research. The ability to monitor the dynamics of vascular and cellular changes in pathological conditions, such as neovascularization or degeneration, longitudinally without the need to sacrifice the mouse, permits longer observation periods in the same animal. With the application of the high-resolution confocal scanning laser ophthalmoscopy in experimental mouse models, access to a large spectrum of imaging modalities in vivo is provided.

  2. Hard Retinal exudates and visual loss due to papilledema

    SciTech Connect

    Rush, J.A.

    1982-02-01

    Bilateral papilledema developed in a patient with a cystic, grade 3 astrocytoma of the right frontal lobe. Despite successful neurosurgical treatment, /sup 60/Co radiotherapy, and oral corticosteroid therapy, progressive visual loss occurred. At examination one year later, visual activity was 20/200 and 20/70, and extensive lipid exudates in the peripapillary retina and central macula of each eye were noted. Retinal lipid exudates rarely complicate the course of surviving patients who had papilledema from intracranial tumor; physicians involved in the multispecialty care of such patients should be aware of the possible ocular residuals of persistent papilledema in an otherwise successfully treated patient.

  3. Tri-functional cannula for retinal endovascular surgery

    DOEpatents

    Weiss, Jonathan D.

    2010-07-27

    A tri-functional cannula combines the functions of tissue Plasminogen Activator (tPA) solution delivery, illumination and venous pressure measurement. The cannula utilizes a tapered hollow-core optical fiber having an inlet for tPA solution, an attached fiber optic splitter configured to receive illumination light from an optical source such and a LED. A window in the cannula transmits the light to and from a central retinal vein. The return light is coupled to an optical detector to measure the pressure within the vein and determine whether an occlusion has been removed.

  4. The bacterial toxin CNF1 as a tool to induce retinal degeneration reminiscent of retinitis pigmentosa

    PubMed Central

    Guadagni, Viviana; Cerri, Chiara; Piano, Ilaria; Novelli, Elena; Gargini, Claudia; Fiorentini, Carla; Caleo, Matteo; Strettoi, Enrica

    2016-01-01

    Retinitis pigmentosa (RP) comprises a group of inherited pathologies characterized by progressive photoreceptor degeneration. In rodent models of RP, expression of defective genes and retinal degeneration usually manifest during the first weeks of postnatal life, making it difficult to distinguish consequences of primary genetic defects from abnormalities in retinal development. Moreover, mouse eyes are small and not always adequate to test pharmacological and surgical treatments. An inducible paradigm of retinal degeneration potentially extensible to large animals is therefore desirable. Starting from the serendipitous observation that intraocular injections of a Rho GTPase activator, the bacterial toxin Cytotoxic Necrotizing Factor 1 (CNF1), lead to retinal degeneration, we implemented an inducible model recapitulating most of the key features of Retinitis Pigmentosa. The model also unmasks an intrinsic vulnerability of photoreceptors to the mechanism of CNF1 action, indicating still unexplored molecular pathways potentially leading to the death of these cells in inherited forms of retinal degeneration. PMID:27775019

  5. Retinal imaging as a source of biomarkers for diagnosis, characterization and prognosis of chronic illness or long-term conditions

    PubMed Central

    Trucco, E; Cameron, J R; Dhillon, B; Houston, J G; van Beek, E J R

    2014-01-01

    The black void behind the pupil was optically impenetrable before the invention of the ophthalmoscope by von Helmholtz over 150 years ago. Advances in retinal imaging and image processing, especially over the past decade, have opened a route to another unexplored landscape, the retinal neurovascular architecture and the retinal ganglion pathways linking to the central nervous system beyond. Exploiting these research opportunities requires multidisciplinary teams to explore the interface sitting at the border between ophthalmology, neurology and computing science. It is from the detail and depth of retinal phenotyping that novel metrics and candidate biomarkers are likely to emerge. Confirmation that in vivo retinal neurovascular measures are predictive of microvascular change in the brain and other organs is likely to be a major area of research activity over the next decade. Unlocking this hidden potential within the retina requires integration of structural and functional data sets, that is, multimodal mapping and longitudinal studies spanning the natural history of the disease process. And with further advances in imaging, it is likely that this area of retinal research will remain active and clinically relevant for many years to come. Accordingly, this review looks at state-of-the-art retinal imaging and its application to diagnosis, characterization and prognosis of chronic illness or long-term conditions. PMID:24936979

  6. Nuclear receptor NR2E3 gene mutations distort human retinal laminar architecture and cause an unusual degeneration.

    PubMed

    Jacobson, Samuel G; Sumaroka, Alexander; Aleman, Tomas S; Cideciyan, Artur V; Schwartz, Sharon B; Roman, Alejandro J; McInnes, Roderick R; Sheffield, Val C; Stone, Edwin M; Swaroop, Anand; Wright, Alan F

    2004-09-01

    Mutations in the nuclear receptor gene, NR2E3, cause a disorder of human retinal photoreceptor development characterized by hyperfunction and excess of the minority S (short wavelength or blue) cone photoreceptor type, but near absence of function of the majority rod receptor. NR2E3 disease can also progress to blindness. How the human retina accommodates mis-specified types and numbers of neurons and advances to retinal degeneration are unknown. We studied the retinal organization in vivo of patients with NR2E3 mutations. Early human NR2E3 disease with S cone hyperfunction showed thickened retinal layers within an otherwise normally structured retina. With visual loss, however, lamination was coarse and there was a strikingly thick and bulging appearance to the retina, localized to an annulus encircling the central fovea. This pattern was not found in other retinal degenerations. The abnormal laminar retinal architecture of early NR2E3 disease may be due in part to larger cells with an S cone phenotype in place of rods that failed to differentiate. The later-stage dysplastic appearance suggests a previously unrecognized proliferative response in human retinal degeneration.

  7. Branch retinal artery occlusion with visual field and multifocal erg in Susac syndrome: a case report.

    PubMed

    van Winden, Marianne; Salu, Paul

    2010-12-01

    A 19-year-old woman presented with subacute encephalopathy and subsequently developed hearing loss and occlusions of branches of the central retinal artery. The triad of microangiopathy of the brain, retina and cochlea is typical for Susac syndrome. The etiology of this syndrome is still unknown, but the prognosis is good in most cases. Spontaneous resolution usually occurs, but early treatment minimizes the risk of sequelae. Multifocal ERG may be useful to assess subclinical retinal dysfunction after recovery of subjective symptoms of BRAO in Susac syndrome.

  8. Re-evaluating the treatment of acute optic neuritis

    PubMed Central

    Bennett, Jeffrey L; Nickerson, Molly; Costello, Fiona; Sergott, Robert C; Calkwood, Jonathan C; Galetta, Steven L; Balcer, Laura J; Markowitz, Clyde E; Vartanian, Timothy; Morrow, Mark; Moster, Mark L; Taylor, Andrew W; Pace, Thaddeus W W; Frohman, Teresa; Frohman, Elliot M

    2015-01-01

    Clinical case reports and prospective trials have demonstrated a reproducible benefit of hypothalamic-pituitary-adrenal (HPA) axis modulation on the rate of recovery from acute inflammatory central nervous system (CNS) demyelination. As a result, corticosteroid preparations and adrenocorticotrophic hormones are the current mainstays of therapy for the treatment of acute optic neuritis (AON) and acute demyelination in multiple sclerosis. Despite facilitating the pace of recovery, HPA axis modulation and corticosteroids have failed to demonstrate long-term benefit on functional recovery. After AON, patients frequently report visual problems, motion perception difficulties and abnormal depth perception despite ‘normal’ (20/20) vision. In light of this disparity, the efficacy of these and other therapies for acute demyelination require re-evaluation using modern, high-precision paraclinical tools capable of monitoring tissue injury. In no arena is this more amenable than AON, where a new array of tools in retinal imaging and electrophysiology has advanced our ability to measure the anatomic and functional consequences of optic nerve injury. As a result, AON provides a unique clinical model for evaluating the treatment response of the derivative elements of acute inflammatory CNS injury: demyelination, axonal injury and neuronal degeneration. In this article, we examine current thinking on the mechanisms of immune injury in AON, discuss novel technologies for the assessment of optic nerve structure and function, and assess current and future treatment modalities. The primary aim is to develop a framework for rigorously evaluating interventions in AON and to assess their ability to preserve tissue architecture, re-establish normal physiology and restore optimal neurological function. PMID:25355373

  9. Anatomy of the retinal nerve fiber layer.

    PubMed

    Radius, R L; de Bruin, J

    1981-11-01

    Anatomy of the retinal nerve fiber layer in rabbit eyes is studied by light microscopy, transmission electron microscopy, and scanning electron microscopy. It is demonstrated that retinal striations noted ophthalmoscopically in these eyes represent individual fiber bundles, Axon bundles are compartmentalized within tissue tunnels comprised of elongated processes of glial cell origin.

  10. Fundus autofluorescence applications in retinal imaging

    PubMed Central

    Gabai, Andrea; Veritti, Daniele; Lanzetta, Paolo

    2015-01-01

    Fundus autofluorescence (FAF) is a relatively new imaging technique that can be used to study retinal diseases. It provides information on retinal metabolism and health. Several different pathologies can be detected. Peculiar AF alterations can help the clinician to monitor disease progression and to better understand its pathogenesis. In the present article, we review FAF principles and clinical applications. PMID:26139802

  11. Fundus autofluorescence applications in retinal imaging.

    PubMed

    Gabai, Andrea; Veritti, Daniele; Lanzetta, Paolo

    2015-05-01

    Fundus autofluorescence (FAF) is a relatively new imaging technique that can be used to study retinal diseases. It provides information on retinal metabolism and health. Several different pathologies can be detected. Peculiar AF alterations can help the clinician to monitor disease progression and to better understand its pathogenesis. In the present article, we review FAF principles and clinical applications.

  12. Bestrophin 1 and retinal disease.

    PubMed

    Johnson, Adiv A; Guziewicz, Karina E; Lee, C Justin; Kalathur, Ravi C; Pulido, Jose S; Marmorstein, Lihua Y; Marmorstein, Alan D

    2017-01-30

    Mutations in the gene BEST1 are causally associated with as many as five clinically distinct retinal degenerative diseases, which are collectively referred to as the "bestrophinopathies". These five associated diseases are: Best vitelliform macular dystrophy, autosomal recessive bestrophinopathy, adult-onset vitelliform macular dystrophy, autosomal dominant vitreoretinochoroidopathy, and retinitis pigmentosa. The most common of these is Best vitelliform macular dystrophy. Bestrophin 1 (Best1), the protein encoded by the gene BEST1, has been the subject of a great deal of research since it was first identified nearly two decades ago. Today we know that Best1 functions as both a pentameric anion channel and a regulator of intracellular Ca(2+) signaling. Best1 is an integral membrane protein which, within the eye, is uniquely expressed in the retinal pigment epithelium where it predominantly localizes to the basolateral plasma membrane. Within the brain, Best1 expression has been documented in both glial cells and astrocytes where it functions in both tonic GABA release and glutamate transport. The crystal structure of Best1 has revealed critical information about how Best1 functions as an ion channel and how Ca(2+) regulates that function. Studies using animal models have led to critical insights into the physiological roles of Best1 and advances in stem cell technology have allowed for the development of patient-derived, "disease in a dish" models. In this article we review our knowledge of Best1 and discuss prospects for near-term clinical trials to test therapies for the bestrophinopathies, a currently incurable and untreatable set of diseases.

  13. Neural reprogramming in retinal degenerations

    PubMed Central

    Marc, Robert E.; Jones, Bryan W.; Anderson, James R.; Kinard, Krista; Marshak, David W.; Wilson, John H.; Wensel, Theodore; Lucas, Robert J.

    2008-01-01

    Purpose Early visual defects in degenerative diseases such as retinitis pigmentosa (RP) may arise from phased remodeling of the neural retina. We sought to explore the functional expression of ionotropic (iGluR) and group III, type 6 metabotropic (mGluR6) glutamate receptors in late-stage photoreceptor degenerations. Methods Excitation mapping with organic cations and computational molecular phenotyping were used to determine whether retinal neurons displayed functional glutamate receptor signaling in rodent models of retinal degenerations and a sample of human RP. Results After photoreceptor loss in rodent models of RP, bipolar cells lose mGluR6 and iGluR glutamate-activated currents, while amacrine and ganglion cells retain iGluR-mediated responsivity. Paradoxically, amacrine and ganglion cells show spontaneous iGluR signals in vivo even though bipolar cells lack glutamate-coupled depolarization mechanisms. Cone survival can rescue iGluR expression by OFF bipolar cells. In a case of human RP with cone sparing, iGluR signaling appeared intact, but the numbers of bipolar cells expressing functional iGluRs was double that of normal retina. Conclusions RP triggers permanent loss of bipolar cell glutamate receptor expression, though spontaneous iGluR-mediated signaling by amacrine and ganglion cells implies that such truncated bipolar cells still release glutamate in response to some non-glutamatergic depolarization. Focal cone-sparing can preserve iGluR display by nearby bipolar cells, which may facilitate late-RP photoreceptor transplant attempts. An instance of human RP provides evidence that rod bipolar cell dendrite switching likely triggers new gene expression patterns and may impair cone pathway function. PMID:17591910

  14. [Viral retinitis following intravitreal triamcinolone injection].

    PubMed

    Zghal, I; Malek, I; Amel, C; Soumaya, O; Bouguila, H; Nacef, L

    2013-09-01

    Necrotizing viral retinitis is associated with infection by the Herpes family of viruses, especially herpes simplex virus (HSV), varicella zoster virus (VZV) and occasionally cytomegalovirus (CMV). When the diagnosis is suspected clinically, antiviral therapy must be instituted immediately. We report the case of a patient presenting with necrotizing viral retinitis 3 months following intravitreal injection of triamcinolone acetonide for diabetic macular edema. Fluorescein angiography demonstrated a superior temporal occlusive vasculitis. A diagnostic anterior chamber paracentesis was performed to obtain deoxyribo-nucleic acid (DNA) for a polymerase chain reaction (PCR) test for viral retinitis. PCR was positive for CMV. The patient was placed on intravenous ganciclovir. CMV retinitis is exceedingly rare in immunocompetent patients; however, it remains the most common cause of posterior uveitis in immunocompromised patients. The incidence of this entity remains unknown. Local immunosuppression, the dose and the frequency of injections may explain the occurrence of this severe retinitis.

  15. The cell stress machinery and retinal degeneration.

    PubMed

    Athanasiou, Dimitra; Aguilà, Monica; Bevilacqua, Dalila; Novoselov, Sergey S; Parfitt, David A; Cheetham, Michael E

    2013-06-27

    Retinal degenerations are a group of clinically and genetically heterogeneous disorders characterised by progressive loss of vision due to neurodegeneration. The retina is a highly specialised tissue with a unique architecture and maintaining homeostasis in all the different retinal cell types is crucial for healthy vision. The retina can be exposed to a variety of environmental insults and stress, including light-induced damage, oxidative stress and inherited mutations that can lead to protein misfolding. Within retinal cells there are different mechanisms to cope with disturbances in proteostasis, such as the heat shock response, the unfolded protein response and autophagy. In this review, we discuss the multiple responses of the retina to different types of stress involved in retinal degenerations, such as retinitis pigmentosa, age-related macular degeneration and glaucoma. Understanding the mechanisms that maintain and re-establish proteostasis in the retina is important for developing new therapeutic approaches to fight blindness.

  16. Oximetry of retinal capillaries by multicomponent analysis.

    PubMed

    Furukawa, Hiromitsu; Arimoto, Hidenobu; Shirai, Tomohiro; Ooto, Sotaro; Hangai, Masanori; Yoshimura, Nagahisa

    2012-08-01

    Retinal oximetry of capillaries was performed for early detection of retinal vascular abnormalities, which are caused predominantly by complications of systemic circulatory diseases. As the conventional method for determining absorbance is not applicable to capillaries, multicomponent analysis was used to estimate the absorbance spectra of the retinal blood vessels. In this analysis, the capillary spectrum was classified as intermediate between those of the retinal arteries and veins, enabling relative estimation of oxygen saturation in the capillaries. This method could be useful for early recognition of disturbances in the peripheral circulation. Furthermore, a spectroscopic ophthalmoscope system based on the proposed method was developed to examine the human retina. A clinical trial of this system demonstrated that oximetry of the retinal capillaries may be an improvement over the present diagnosis for patients of malignant hypertension.

  17. Chronic ocular hypertension alters local retinal responsiveness.

    PubMed Central

    Ofri, R; Dawson, W W; Foli, K; Gelatt, K N

    1993-01-01

    Electrophysiological responses of the retina and visual cortex to a series of grating stimuli (6-768 minutes of arc) were recorded in seven sessions using normal beagles, 21 sessions using beagles afflicted with inherited ocular hypertension, and 12 sessions using rhesus monkeys. A 15 degrees field centred around the animal's area centralis or fovea was used to stimulate the central retina. A 30 degrees field, centred on the same spot, was then used to stimulate the larger area. Two recording series were completed on each animal, with both field sizes presented in each recording session. The first recording took place 30 minutes after and the second 2 hours after the injection of thiamylal sodium. Only the signals from the toroidal 15 degrees of the retina of the hypertensive dogs were remarkably larger during the second recording (p = 0.001). No significant differences were found between the two recordings from the retinas of normal dogs or monkeys, nor were there any significant differences between the two recordings from above the cortex in any group. Several hypotheses are proposed to explain the basis for the interaction of thiamylal with the more peripheral retinal function in clinically glaucomatous dogs. PMID:8025048

  18. Effects of central activation of serotonin 5-HT2A/2C or dopamine D2/3 receptors on the acute and repeated effects of clozapine in the conditioned avoidance response test

    PubMed Central

    Feng, Min; Gao, Jun; Sui, Nan; Li, Ming

    2014-01-01

    Rationale: Acute administration of clozapine (a gold standard of atypical antipsychotics) disrupts avoidance response in rodents, while repeated administration often causes a tolerance effect. Objective: The present study investigated the neuroanatomical basis and receptor mechanisms of acute and repeated effects of clozapine treatment in the conditioned avoidance response test in male Sprague-Dawley rats. Methods: DOI (2,5-dimethoxy-4-iodo-amphetamine, a preferential 5-HT2A/2C agonist) or quinpirole (a preferential dopamine D2/3 agonist) was microinjected into the medial prefrontal cortex (mPFC) or nucleus accumbens shell (NAs), and their effects on the acute and long-term avoidance-disruptive effect of clozapine were tested. Results: Intra-mPFC microinjection of quinpirole enhanced the acute avoidance disruptive effect of clozapine (10 mg/kg, sc), while DOI microinjections reduced it marginally. Repeated administration of clozapine (10 mg/kg, sc) daily for 5 days caused a progressive decrease in its inhibition of avoidance responding, indicating tolerance development. Intra-mPFC microinjection of DOI at 25.0 (but not 5.0) μg/side during this period completely abolished the expression of clozapine tolerance. This was indicated by the finding that clozapine-treated rats centrally infused with 25.0 μg/side DOI did not show higher levels of avoidance responses than the vehicle-treated rats in the clozapine challenge test. Microinjection of DOI into the mPFC immediately before the challenge test also decreased the expression of clozapine tolerance. Conclusions: Acute behavioral effect of clozapine can be enhanced by activation of the D2/3 receptors in the mPFC. Clozapine tolerance expression relies on the neuroplasticity initiated by its antagonist action against 5-HT2A/2C receptors in the mPFC. PMID:25288514

  19. Cannabinoid receptors and TRPA1 on neuroprotection in a model of retinal ischemia.

    PubMed

    Araújo, D S M; Miya-Coreixas, V S; Pandolfo, P; Calaza, K C

    2017-01-01

    Retinal ischemia is a pathological event present in several retinopathies such as diabetic retinopathy and glaucoma, leading to partial or full blindness with no effective treatment available. Since synthetic and endogenous cannabinoids have been studied as modulators of ischemic events in the central nervous system (CNS), the present study aimed to investigate the involvement of cannabinoid system in the cell death induced by ischemia in an avascular (chick) retina. We observed that chick retinal treatment with a combination of WIN 55212-2 and cannabinoid receptor antagonists (either AM251/O-2050 or AM630) decreased the release of lactate dehydrogenase (LDH) induced by retinal ischemia in an oxygen and glucose deprivation (OGD) model. Further, the increased availability of endocannabinoids together with cannabinoid receptor antagonists also had a neuroprotective effect. Surprisingly, retinal exposure to any of these drugs alone did not prevent the release of LDH stimulated by OGD. Since cannabinoids may also activate transient receptor potential (TRP) channels, we investigated the involvement of TRPA1 receptors (TRPA1) in retinal cell death induced by ischemic events. We demonstrated the presence of TRPA1 in the chick retina, and observed an increase in TRPA1 content after OGD, both by western blot and immunohistochemistry. In addition, the selective activation of TRPA1 by mustard oil (MO) did not worsen retinal LDH release induced by OGD, whereas the blockage of TRPA1 completely prevented the extravasation of cellular LDH in ischemic condition. Hence, these results show that during the ischemic event there is an augment of TRPA1, and activation of this receptor is important in cell death induction. The data also indicate that metabotropic cannabinoid receptors, both type 1 and 2, are not involved with the cell death found in the early stages of ischemia. Therefore, the study points to a potential role of TRPA1 as a target for neuroprotective approaches in retinal

  20. Honokiol inhibits pathological retinal neovascularization in oxygen-induced retinopathy mouse model

    SciTech Connect

    Vavilala, Divya Teja; O’Bryhim, Bliss E.; Ponnaluri, V.K. Chaithanya; White, R. Sid; Radel, Jeff; Symons, R.C. Andrew; Mukherji, Mridul

    2013-09-06

    Highlights: •Aberrant activation of HIF pathway is the underlying cause of ischemic neovascularization. •Honokiol has better therapeutic index as a HIF inhibitor than digoxin and doxorubicin. •Daily IP injection of honokiol in OIR mouse model reduced retinal neovascularization. •Honokiol also prevents vaso-obliteration, the characteristic feature of the OIR model. •Honokiol enhanced physiological revascularization of the retinal vascular plexuses. -- Abstract: Aberrant activation of the hypoxia inducible factor (HIF) pathway is the underlying cause of retinal neovascularization, one of the most common causes of blindness worldwide. The HIF pathway also plays critical roles during tumor angiogenesis and cancer stem cell transformation. We have recently shown that honokiol is a potent inhibitor of the HIF pathway in a number of cancer and retinal pigment epithelial cell lines. Here we evaluate the safety and efficacy of honokiol, digoxin, and doxorubicin, three recently identified HIF inhibitors from natural sources. Our studies show that honokiol has a better safety to efficacy profile as a HIF inhibitor than digoxin and doxorubicin. Further, we show for the first time that daily intraperitoneal injection of honokiol starting at postnatal day (P) 12 in an oxygen-induced retinopathy (OIR) mouse model significantly reduced retinal neovascularization at P17. Administration of honokiol also prevents the oxygen-induced central retinal vaso-obliteration, characteristic feature of the OIR model. Additionally, honokiol enhanced physiological revascularization of the retinal vascular plexuses. Since honokiol suppresses multiple pathways activated by HIF, in addition to the VEGF signaling, it may provide advantages over current treatments utilizing specific VEGF antagonists for ocular neovascular diseases and cancers.

  1. Evaluation of Retinal Vessel Morphology in Patients with Parkinson's Disease Using Optical Coherence Tomography

    PubMed Central

    Hidding, Ute; Keserü, Matthias; Keserü, Diana; Hassenstein, Andrea; Stemplewitz, Birthe

    2016-01-01

    Purpose The retina has been found affected in Parkinson’s disease (PD). It is unclear if this is due to neurodegeneration of local dopamine-dependent retinal cells, a result of central nervous degeneration including the optic nerve or retinal small vessel disease. This study aimed to detect changes of the retinal vasculature in PD patients compared to controls. Methods We examined 49 PD patients and 49 age- and sex-matched healthy controls by spectral domain optical coherence tomography (SD-OCT) with a circular scan centred at the optic disc. Vessels within the retinal nerve fibre layer were identified by an automated algorithm and thereafter manually labelled as artery or vein. Layer segmentation, vessel lumen and direct surrounding tissue were marked automatically with a grey value and the contrast between both values in relation to the surrounding tissue was calculated. The differences in these grey value ratios among subjects were determined and used as an indicator for differences in vessel morphology. Furthermore, the diameters of the veins and arteries were measured and then compared between the groups. Results The contrast of retinal veins was significantly lower in PD patients compared to controls, which indicates changes in vessel morphology in PD. The contrast of arteries was not significantly different. Disease duration, disease stage according to Hoehn and Yahr or age did not influence the grey value ratios in PD patients. Vessel diameter in either veins or arteries did not differ between subject groups. The contrast of retinal veins contralateral to the clinically predominant and first affected side was significantly lower compared to the ipsilateral side. Conclusion Our data show a potential difference of the retinal vasculature in PD patients compared to controls. Vascular changes in the retina of PD patients might contribute to vision-related complaints in PD. PMID:27525728

  2. High-Resolution Quantitative Immunogold Analysis of Membrane Receptors at Retinal Ribbon Synapses.

    PubMed

    Zhang, Jun; Petralia, Ronald S; Wang, Ya-Xian; Diamond, Jeffrey S

    2016-02-18

    Retinal ganglion cells (RGCs) receive excitatory glutamatergic input from bipolar cells. Synaptic excitation of RGCs is mediated postsynaptically by NMDA receptors (NMDARs) and AMPA receptors (AMPARs). Physiological data have indicated that glutamate receptors at RGCs are expressed not only in postsynaptic but also in perisynaptic or extrasynaptic membrane compartments. However, precise anatomical locations for glutamate receptors at RGC synapses have not been determined. Although a high-resolution quantitative analysis of glutamate receptors at central synapses is widely employed, this approach has had only limited success in the retina. We developed a postembedding immunogold method for analysis of membrane receptors, making it possible to estimate the number, density and variability of these receptors at retinal ribbon synapses. Here we describe the tools, reagents, and the practical steps that are needed for: 1) successful preparation of retinal fixation, 2) freeze-substitution, 3) postembedding immunogold electron microscope (EM) immunocytochemistry and, 4) quantitative visualization of glutamate receptors at ribbon synapses.

  3. Line-field parallel swept source MHz OCT for structural and functional retinal imaging.

    PubMed

    Fechtig, Daniel J; Grajciar, Branislav; Schmoll, Tilman; Blatter, Cedric; Werkmeister, Rene M; Drexler, Wolfgang; Leitgeb, Rainer A

    2015-03-01

    We demonstrate three-dimensional structural and functional retinal imaging with line-field parallel swept source imaging (LPSI) at acquisition speeds of up to 1 MHz equivalent A-scan rate with sensitivity better than 93.5 dB at a central wavelength of 840 nm. The results demonstrate competitive sensitivity, speed, image contrast and penetration depth when compared to conventional point scanning OCT. LPSI allows high-speed retinal imaging of function and morphology with commercially available components. We further demonstrate a method that mitigates the effect of the lateral Gaussian intensity distribution across the line focus and demonstrate and discuss the feasibility of high-speed optical angiography for visualization of the retinal microcirculation.

  4. Line-field parallel swept source MHz OCT for structural and functional retinal imaging

    PubMed Central

    Fechtig, Daniel J.; Grajciar, Branislav; Schmoll, Tilman; Blatter, Cedric; Werkmeister, Rene M.; Drexler, Wolfgang; Leitgeb, Rainer A.

    2015-01-01

    We demonstrate three-dimensional structural and functional retinal imaging with line-field parallel swept source imaging (LPSI) at acquisition speeds of up to 1 MHz equivalent A-scan rate with sensitivity better than 93.5 dB at a central wavelength of 840 nm. The results demonstrate competitive sensitivity, speed, image contrast and penetration depth when compared to conventional point scanning OCT. LPSI allows high-speed retinal imaging of function and morphology with commercially available components. We further demonstrate a method that mitigates the effect of the lateral Gaussian intensity distribution across the line focus and demonstrate and discuss the feasibility of high-speed optical angiography for visualization of the retinal microcirculation. PMID:25798298

  5. Advancing therapeutic strategies for inherited retinal degeneration: recommendations from the Monaciano Symposium.

    PubMed

    Thompson, Debra A; Ali, Robin R; Banin, Eyal; Branham, Kari E; Flannery, John G; Gamm, David M; Hauswirth, William W; Heckenlively, John R; Iannaccone, Alessandro; Jayasundera, K Thiran; Khan, Naheed W; Molday, Robert S; Pennesi, Mark E; Reh, Thomas A; Weleber, Richard G; Zacks, David N

    2015-02-09

    Although rare in the general population, retinal dystrophies occupy a central position in current efforts to develop innovative therapies for blinding diseases. This status derives, in part, from the unique biology, accessibility, and function of the retina, as well as from the synergy between molecular discoveries and transformative advances in functional assessment and retinal imaging. The combination of these factors has fueled remarkable progress in the field, while at the same time creating complex challenges for organizing collective efforts aimed at advancing translational research. The present position paper outlines recent progress in gene therapy and cell therapy for this group of disorders, and presents a set of recommendations for addressing the challenges remaining for the coming decade. It is hoped that the formulation of these recommendations will stimulate discussions among researchers, funding agencies, industry, and policy makers that will accelerate the development of safe and effective treatments for retinal dystrophies and related diseases.

  6. Advancing Therapeutic Strategies for Inherited Retinal Degeneration: Recommendations From the Monaciano Symposium

    PubMed Central

    Thompson, Debra A.; Ali, Robin R.; Banin, Eyal; Branham, Kari E.; Flannery, John G.; Gamm, David M.; Hauswirth, William W.; Heckenlively, John R.; Iannaccone, Alessandro; Jayasundera, K. Thiran; Khan, Naheed W.; Molday, Robert S.; Pennesi, Mark E.; Reh, Thomas A.; Weleber, Richard G.; Zacks, David N.

    2015-01-01

    Although rare in the general population, retinal dystrophies occupy a central position in current efforts to develop innovative therapies for blinding diseases. This status derives, in part, from the unique biology, accessibility, and function of the retina, as well as from the synergy between molecular discoveries and transformative advances in functional assessment and retinal imaging. The combination of these factors has fueled remarkable progress in the field, while at the same time creating complex challenges for organizing collective efforts aimed at advancing translational research. The present position paper outlines recent progress in gene therapy and cell therapy for this group of disorders, and presents a set of recommendations for addressing the challenges remaining for the coming decade. It is hoped that the formulation of these recommendations will stimulate discussions among researchers, funding agencies, industry, and policy makers that will accelerate the development of safe and effective treatments for retinal dystrophies and related diseases. PMID:25667399

  7. Construction of a plasmid for human brain-derived neurotrophic factor and its effect on retinal pigment epithelial cell viability

    PubMed Central

    Yan, Bo-jing; Wu, Zhi-zhong; Chong, Wei-hua; Li, Gen-lin

    2016-01-01

    Several studies have investigated the protective functions of brain-derived neurotrophic factor (BDNF) in retinitis pigmentosa. However, a BDNF-based therapy for retinitis pigmentosa is not yet available. To develop an efficient treatment for fundus disease, an eukaryotic expression plasmid was generated and used to transfect human 293T cells to assess the expression and bioactivity of BDNF on acute retinal pigment epithelial-19 (ARPE-19) cells, a human retinal epithelial cell line. After 96 hours of co-culture in a Transwell chamber, ARPE-19 cells exposed to BDNF secreted by 293T cells were more viable than ARPE-19 cells not exposed to secreted BDNF. Western blot assay showed that Bax levels were downregulated and that Bcl-2 levels were upregulated in human ARPE-19 cells exposed to BDNF. Furthermore, 293T cells transfected with the BDNF gene steadily secreted the protein. The powerful anti-apoptotic function of this BDNF may be useful for the treatment of retinitis pigmentosa and other retinal degenerative diseases. PMID:28197196

  8. Progressive outer retinal necrosis syndrome: a comprehensive review of its clinical presentation, relationship to immune system status, and management.

    PubMed

    Austin

    2000-12-01

    Progressive outer retinal necrosis (PORN) syndrome is a form of the Varicella zoster virus (VZV) chorioretinitis found almost exclusively in people with the acquired immunodeficiency syndrome (AIDS). This destructive infection has an extremely rapid course that may lead to no light perception in affected eyes within days or weeks. Attempts at its treatment have had limited success. Rhegmatogenous retinal detachments often occur after the development of atrophic retinal holes, and silicone oil temponade has been found to be the most successful reattachment procedure. Unfortunately, cataract formation is common after such surgery. PORN needs to be differentiated from acute retinal necrosis (ARN) syndrome, a necrotizing retinitis that can also be caused by VZV. PORN and ARN are found at opposite ends of the spectrum of necrotizing herpetic retinopathies (NHR), where its clinical presentation depends upon immune system status. After a brief case presentation, the distinguishing clinical characteristics of PORN, its differentiation from ARN, attempts at its treatment, the role of the immune system status on its clinical appearance and treatment, and management of complications such as retinal detachment and subsequent cataracts are discussed.

  9. Acute disseminated encephalomyelitis.

    PubMed

    Alper, Gulay

    2012-11-01

    Acute disseminated encephalomyelitis is an immune-mediated inflammatory and demyelinating disorder of the central nervous system, commonly preceded by an infection. It principally involves the white matter tracts of the cerebral hemispheres, brainstem, optic nerves, and spinal cord. Acute disseminated encephalomyelitis mainly affects children. Clinically, patients present with multifocal neurologic abnormalities reflecting the widespread involvement in central nervous system. Cerebrospinal fluid may be normal or may show a mild pleocytosis with or without elevated protein levels. Magnetic resonance image (MRI) shows multiple demyelinating lesions. The diagnosis of acute disseminated encephalomyelitis requires both multifocal involvement and encephalopathy by consensus criteria. Acute disseminated encephalomyelitis typically has a monophasic course with a favorable prognosis. Multiphasic forms have been reported, resulting in diagnostic difficulties in distinguishing these cases from multiple sclerosis. In addition, many inflammatory disorders may have a similar presentation with frequent occurrence of encephalopathy and should be considered in the differential diagnosis of acute disseminated encephalomyelitis.

  10. Platelet-derived growth factor (PDGF)-C inhibits neuroretinal apoptosis in a murine model of focal retinal degeneration.

    PubMed

    Wang, Yujuan; Abu-Asab, Mones S; Yu, Cheng-Rong; Tang, Zhongshu; Shen, Defen; Tuo, Jingsheng; Li, Xuri; Chan, Chi-Chao

    2014-06-01

    Platelet-derived growth factor (PDGF)-C is a member of the PDGF family and is critical for neuronal survival in the central nervous system. We studied the possible survival and antiapoptotic effects of PDGF-C on focal retinal lesions in Ccl2(-/-)/Cx3cr1(-/-) on C57BL/6N [Crb1(rd8)] (DKO rd8) background mice, a model for progressive and focal retinal degeneration. We found no difference in transcript and protein expression of PDGF-C in the retina between DKO rd8 mice and wild type (WT, C57BL/6N). Recombinant PDGF-CC protein (500 ng/eye) was injected intravitreally into the right eye of DKO rd8 mice with phosphate-buffered saline as controls into the left eye. The retinal effects of PDGF-C were assessed by fundoscopy, ocular histopathology, A2E levels, apoptotic molecule analysis, and direct flat mount retinal vascular labeling. We found that the PDGF-CC-treated eyes showed slower progression or attenuation of the focal retinal lesions, lesser photoreceptor and retinal pigment epithelial degeneration resulting in better-preserved photoreceptor structure. Lower expression of apoptotic molecules was detected in the PDGF-CC-treated eyes than in controls. In addition, no retinal neovascularization was observed after PDGF-CC treatment. Our results demonstrate that PDGF-C potently ameliorates photoreceptor degeneration via the suppression of apoptotic pathways without inducing retinal angiogenesis. The protective effects of PDGF-C suggest a novel alternative approach for potential age-related retinal degeneration treatment.

  11. Genetic linkage studies in autosomal recessive retinitis pigmentosa

    SciTech Connect

    Mansfield, D.C.; Teague, P.W.; Barber, A.

    1994-09-01

    Autosomal recessive retinitis pigmentosa (arRP) is a severe retinal dystrophy characterized by night blindness, progressive constriction of the visual fields and loss of central vision in the fourth or fifth decades. The frequency of this form of retinitis pigmentosa (RP) varies in different populations. Mutations within the rhodopsin, cyclic GMP phosphodiesterase-{beta} subunit and cGMP-gated channel genes have been reported in some arRP families. The genetic loci responsible for the majority of cases have yet to be identified. Genetic heterogeneity is likely to be extensive. In order to minimize the amount of genetic heterogenity, a set of arRP families was ascertained within the South-Central Sardinian population, in which 81% of families with a known mode of inheritance show an autosomal recessive form of RP. The Sardinian population is an ethnic {open_quotes}outlier{close_quotes}, having remained relatively isolated from mainland and other cultures. Genetic linkage data has been obtained in a set of 11 Sardinian arRP kindreds containing 26 affected members. Under the assumption of genetic homogeneity, no evidence of linkage was found in the arRP kindreds using 195 markers, which excluded 62% of the genome (Z<-2). Positive lod scores were obtained with D14S80 which showed no recombination in a subset of 5 families. Heterogeneity testing using D14S80 and arRP showed no significant evidence of heterogeneity (p=0.18) but evidence of linkage ({chi}{sup 2}=3.64, p=0.028). We are currently screening the neural retina-specific leucine zipper gene (NRL) in 14q11 for mutations as a candidate locus.

  12. Fixation strategies for retinal immunohistochemistry.

    PubMed

    Stradleigh, Tyler W; Ishida, Andrew T

    2015-09-01

    Immunohistochemical and ex vivo anatomical studies have provided many glimpses of the variety, distribution, and signaling components of vertebrate retinal neurons. The beauty of numerous images published to date, and the qualitative and quantitative information they provide, indicate that these approaches are fundamentally useful. However, obtaining these images entailed tissue handling and exposure to chemical solutions that differ from normal extracellular fluid in composition, temperature, and osmolarity. Because the differences are large enough to alter intercellular and intracellular signaling in neurons, and because retinae are susceptible to crush, shear, and fray, it is natural to wonder if immunohistochemical and anatomical methods disturb or damage the cells they are designed to examine. Tissue fixation is typically incorporated to guard against this damage and is therefore critically important to the quality and significance of the harvested data. Here, we describe mechanisms of fixation; advantages and disadvantages of using formaldehyde and glutaraldehyde as fixatives during immunohistochemistry; and modifications of widely used protocols that have recently been found to improve cell shape preservation and immunostaining patterns, especially in proximal retinal neurons.

  13. Measurement of retinal blood velocity

    NASA Astrophysics Data System (ADS)

    Winchester, Leonard W., Jr.; Chou, Nee-Yin

    2006-02-01

    A fundus camera was modified to illuminate the retina of a rabbit model with low power laser light in order to obtain laser speckle images. A fast-exposure charge-coupled device (CCD) camera was used to capture laser speckle images of the retina. Image acquisition was synchronized with the arterial pulses of the rabbit to ensure that all images are obtained at the same point in the cardiac cycle. The rabbits were sedated and a speculum was inserted to prevent the eyelid from closing. Both albino (New Zealand; pigmented (Dutch belted) rabbits were used in the study. The rabbit retina is almost avascular. The measurements are obtained for choroidal tissue as well as retinal tissue. Because the retina is in a region of high metabolism, blood velocity is strongly affected by blood oxygen saturation. Measurements of blood velocity obtained over a wide range of O II saturations (58%-100%) showed that blood velocity increases with decreasing O II saturation. For most experiments, the left eye of the rabbit was used for laser measurements whereas the right eye served as a control. No observable difference between pre- and post-experimented eye was noted. Histological examinations of retinal tissue subjected to repeated laser measurements showed no indication of tissue damage.

  14. Fixation Strategies For Retinal Immunohistochemistry

    PubMed Central

    Stradleigh, Tyler W.; Ishida, Andrew T.

    2015-01-01

    Immunohistochemical and ex vivo anatomical studies have provided many glimpses of the variety, distribution, and signaling components of vertebrate retinal neurons. The beauty of numerous images published to date, and the qualitative and quantitative information they provide, indicate that these approaches are fundamentally useful. However, obtaining these images entailed tissue handling and exposure to chemical solutions that differ from normal extracellular fluid in composition, temperature, and osmolarity. Because the differences are large enough to alter intercellular and intracellular signaling in neurons, and because retinae are susceptible to crush, shear, and fray, it is natural to wonder if immunohistochemical and anatomical methods disturb or damage the cells they are designed to examine. Tissue fixation is typically incorporated to guard against this damage and is therefore critically important to the quality and significance of the harvested data. Here, we describe mechanisms of fixation; advantages and disadvantages of using formaldehyde and glutaraldehyde as fixatives during immunohistochemistry; and modifications of widely used protocols that have recently been found to improve cell shape preservation and immunostaining patterns, especially in proximal retinal neurons. PMID:25892361

  15. RPGR-Associated Retinal Degeneration in Human X-Linked RP and a Murine Model

    PubMed Central

    Huang, Wei Chieh; Wright, Alan F.; Roman, Alejandro J.; Cideciyan, Artur V.; Manson, Forbes D.; Gewaily, Dina Y.; Schwartz, Sharon B.; Sadigh, Sam; Limberis, Maria P.; Bell, Peter; Wilson, James M.; Swaroop, Anand; Jacobson, Samuel G.

    2012-01-01

    Purpose. We investigated the retinal disease due to mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene in human patients and in an Rpgr conditional knockout (cko) mouse model. Methods. XLRP patients with RPGR-ORF15 mutations (n = 35, ages at first visit 5–72 years) had clinical examinations, and rod and cone perimetry. Rpgr-cko mice, in which the proximal promoter and first exon were deleted ubiquitously, were back-crossed onto a BALB/c background, and studied with optical coherence tomography and electroretinography (ERG). Retinal histopathology was performed on a subset. Results. Different patterns of rod and cone dysfunction were present in patients. Frequently, there were midperipheral losses with residual rod and cone function in central and peripheral retina. Longitudinal data indicated that central rod loss preceded peripheral rod losses. Central cone-only vision with no peripheral function was a late stage. Less commonly, patients had central rod and cone dysfunction, but preserved, albeit abnormal, midperipheral rod and cone vision. Rpgr-cko mice had progressive retinal degeneration detectable in the first months of life. ERGs indicated relatively equal rod and cone disease. At late stages, there was greater inferior versus superior retinal degeneration. Conclusions. RPGR mutations lead to progressive loss of rod and cone vision, but show different patterns of residual photoreceptor disease expression. Knowledge of the patterns should guide treatment strategies. Rpgr-cko mice had onset of degeneration at relatively young ages and progressive photoreceptor disease. The natural history in this model will permit preclinical proof-of-concept studies to be designed and such studies should advance progress toward human therapy. PMID:22807293

  16. Neural remodeling in retinal degeneration.

    PubMed

    Marc, Robert E; Jones, Bryan W; Watt, Carl B; Strettoi, Enrica

    2003-09-01

    Mammalian retinal degenerations initiated by gene defects in rods, cones or the retinal pigmented epithelium (RPE) often trigger loss of the sensory retina, effectively leaving the neural retina deafferented. The neural retina responds to this challenge by remodeling, first by subtle changes in neuronal structure and later by large-scale reorganization. Retinal degenerations in the mammalian retina generally progress through three phases. Phase 1 initiates with expression of a primary insult, followed by phase 2 photoreceptor death that ablates the sensory retina via initial photoreceptor stress, phenotype deconstruction, irreversible stress and cell death, including bystander effects or loss of trophic support. The loss of cones heralds phase 3: a protracted period of global remodeling of the remnant neural retina. Remodeling resembles the responses of many CNS assemblies to deafferentation or trauma, and includes neuronal cell death, neuronal and glial migration, elaboration of new neurites and synapses, rewiring of retinal circuits, glial hypertrophy and the evolution of a fibrotic glial seal that isolates the remnant neural retina from the surviving RPE and choroid. In early phase 2, stressed photoreceptors sprout anomalous neurites that often reach the inner plexiform and ganglion cell layers. As death of rods and cones progresses, bipolar and horizontal cells are deafferented and retract most of their dendrites. Horizontal cells develop anomalous axonal processes and dendritic stalks that enter the inner plexiform layer. Dendrite truncation in rod bipolar cells is accompanied by revision of their macromolecular phenotype, including the loss of functioning mGluR6 transduction. After ablation of the sensory retina, Müller cells increase intermediate filament synthesis, forming a dense fibrotic layer in the remnant subretinal space. This layer invests the remnant retina and seals it from access via the choroidal route. Evidence of bipolar cell death begins in

  17. Primary visual cortical remapping in patients with inherited peripheral retinal degeneration.

    PubMed

    Ferreira, Sónia; Pereira, Andreia Carvalho; Quendera, Bruno; Reis, Aldina; Silva, Eduardo Duarte; Castelo-Branco, Miguel

    2017-01-01

    Human studies addressing the long-term effects of peripheral retinal degeneration on visual cortical function and structure are scarce. Here we investigated this question in patients with Retinitis Pigmentosa (RP), a genetic condition leading to peripheral visual degeneration. We acquired functional and anatomical magnetic resonance data from thirteen patients with different levels of visual loss and twenty-two healthy participants to study primary (V1) visual cortical retinotopic remapping and cortical thickness. We identified systematic visual field remapping in the absence of structural changes in the primary visual cortex of RP patients. Remapping consisted in a retinotopic eccentricity shift of central retinal inputs to more peripheral locations in V1. Importantly, this was associated with changes in visual experience, as assessed by the extent of the visual loss, with more constricted visual fields resulting in larger remapping. This pattern of remapping is consistent with expansion or shifting of neuronal receptive fields into the cortical regions with reduced retinal input. These data provide evidence for functional changes in V1 that are dependent on the magnitude of peripheral visual loss in RP, which may be explained by rapid cortical adaptation mechanisms or long-term cortical reorganization. This study highlights the importance of analyzing the retinal determinants of brain functional and structural alterations for future visual restoration approaches.

  18. The clinical features of retinal disease due to a dominant mutation in RPE65

    PubMed Central

    Hull, Sarah; Mukherjee, Rajarshi; Holder, Graham E.; Moore, Anthony T.

    2016-01-01

    Purpose To present a detailed phenotypic and molecular study of two families with autosomal dominant RPE65-related retinal dystrophy. Methods Five patients from two families were ascertained from the retinal clinics of a tertiary referral center. Phenotyping included retinal imaging and electrophysiological testing. Bidirectional Sanger sequencing of exon 13 of RPE65 and its intron–exon boundaries was performed on all reported patients and segregation confirmed in available relatives. The main outcome measures were the results of an ophthalmic examination and investigation and molecular genetic analysis. Results Four affected patients from two families presented with nyctalopia and central visual disturbance in adulthood progressing to severe visual loss by the fifth to eighth decades. The patients had extensive chorioretinal atrophy with a relatively preserved anterior retina. In the second family, one patient had bilateral, vitelliform-like foveal lesions consistent with adult onset vitelliform macular dystrophy and no peripheral retinal changes. These unrelated families were both heterozygous for c.1430A>G (p.Asp477Gly). One unaffected family member also tested positive for this mutation but had good vision at age 80 years. Conclusions Autosomal dominant retinal dystrophy resembling choroideremia can arise from a heterozygous mutation in RPE65. It may manifest with mild disease or be non-penetrant. Awareness of these unusual presentations can facilitate targeted molecular investigation. PMID:27307694

  19. Persistent inflammatory state after photoreceptor loss in an animal model of retinal degeneration

    PubMed Central

    Noailles, Agustina; Maneu, Victoria; Campello, Laura; Gómez-Vicente, Violeta; Lax, Pedro; Cuenca, Nicolás

    2016-01-01

    Microglia act as the resident immune cells of the central nervous system, including the retina. In response to damaging stimuli microglia adopt an activated state, which can progress into a phagocytic phenotype and play a potentially harmful role by eliciting the expression and release of pro-inflammatory cytokines. The aim of the present study was to assess longitudinal changes in microglia during retinal degeneration in the homozygous P23H rat, a model of dominant retinitis pigmentosa. Microglial phenotypes, morphology and density were analyzed by immunohistochemistry, flow cytometry, and cytokine antibody array. In addition, we performed electroretinograms to evaluate the retinal response. In the P23H retina, sclera, choroid and ciliary body, inflammatory cells increased in number compared with the control at all ages analyzed. As the rats became older, a higher number of amoeboid MHC-II+ cells were observed in the P23H retina, which correlated with an increase in the expression of pro-inflammatory cytokines. These findings suggest that, in the P23H model, retinal neuroinflammation persists throughout the rat’s life span even after photoreceptor depletion. Therefore, the inclusion of anti-inflammatory drugs at advanced stages of the neurodegenerative process may provide better retinal fitness so the remaining cells could still be used as targets of cellular or gene therapies. PMID:27624537

  20. Automated retinal image analysis over the internet.

    PubMed

    Tsai, Chia-Ling; Madore, Benjamin; Leotta, Matthew J; Sofka, Michal; Yang, Gehua; Majerovics, Anna; Tanenbaum, Howard L; Stewart, Charles V; Roysam, Badrinath

    2008-07-01

    Retinal clinicians and researchers make extensive use of images, and the current emphasis is on digital imaging of the retinal fundus. The goal of this paper is to introduce a system, known as retinal image vessel extraction and registration system, which provides the community of retinal clinicians, researchers, and study directors an integrated suite of advanced digital retinal image analysis tools over the Internet. The capabilities include vasculature tracing and morphometry, joint (simultaneous) montaging of multiple retinal fields, cross-modality registration (color/red-free fundus photographs and fluorescein angiograms), and generation of flicker animations for visualization of changes from longitudinal image sequences. Each capability has been carefully validated in our previous research work. The integrated Internet-based system can enable significant advances in retina-related clinical diagnosis, visualization of the complete fundus at full resolution from multiple low-angle views, analysis of longitudinal changes, research on the retinal vasculature, and objective, quantitative computer-assisted scoring of clinical trials imagery. It could pave the way for future screening services from optometry facilities.

  1. Lipoprotein(a), homocysteine, and retinal arteriosclerosis

    PubMed Central

    Javadzadeh, Alireza; Argani, Hassan; Nezami, Nariman; Rashtchizadeh, Nadereh; Rafeey, Mandana; Rohbaninoubar, Mohammad; Rahimi-Ardabili, Babak

    2008-01-01

    Purpose Elevated levels of lipoprotein(a) [Lp(a)] and homocysteine (Hcy) have been implicated as risk factors for vascular diseases. The study was performed to explore the possible relationship between retinal arteriosclerosis and serum Lp(a) and Hcy levels. Methods Study subjects consisted of 80 nonsmoking male patients with retinal arteriosclerosis and 54 healthy nonsmoker males as controls. Retinal arteriosclerosis was graded according to the Scheie classification. Serum levels of lipids, lipoproteins, Lp(a), and Hcy were measured by standard methods. Results The serum level of Hcy was higher in patients (24.2±8.1 μmol/l) than controls (10.5±4.1 μmol/l); p<0.01. Serum levels of Lp(a) in patients (47.9±33.1 mg/dl) was also higher than controls (11.7±7.6 mg/dl); p<0.01. There was a significant direct linear correlation between the degree of retinal arteriosclerosis and Lp(a) level (r=0.61, p<0.01), the degree of retinal arteriosclerosis and Hcy level (r=0.72, p<0.01), and also between Lp(a) and Hcy levels (r=0.67, p<0.01). Conclusions The association between retinal arteriosclerosis and serum Lp(a) and Hcy levels suggests that Lp(a) as well as Hcy could play a role in the development of retinal arteriosclerosis. PMID:18806883

  2. Digital tracking and control of retinal images

    NASA Astrophysics Data System (ADS)

    Barrett, Steven F.; Jerath, Maya R.; Rylander, Henry G., III; Welch, Ashley J.

    1993-06-01

    Laser induced retinal lesions are used to treat a variety of eye diseases such as diabetic retinopathy and retinal detachment. An instrumentation system has been developed to track a specific lesion coordinate on the retinal surface and provide corrective signals to maintain laser position on the coordinate. High resolution retinal images are acquired via a CCD camera coupled to a fundus camera and video frame grabber. Optical filtering and histogram modification are used to enhance the retinal vessel network against the lighter retinal background. Six distinct retinal landmarks are tracked on the high contrast image obtained from the frame grabber using two-dimensional blood vessel templates. The frame grabber is hosted on a 486 PC. The PC performs correction signal calculations using an exhaustive search on selected image portions. An X and Y laser correction signal is derived from the landmark tracking information and provided to a pair of galvanometer steered mirrors via a data acquisition and control subsystem. This subsystem also responds to patient inputs and the system monitoring lesion growth. This paper begins with an overview of the robotic laser system design followed by implementation and testi