We have expanded our efforts to generate high spatial resolution images showing the distibution of carotenoid macular pigments in the human retina using Raman spectroscopy. A low level of macular pigments is associated with an increased risk of developing age-related macular degeneration, a leading cause of irreversible blindness. Using excised human eyecups and resonant excitation of the pigment molecules with narrow bandwidth blue light from a filtered arc lamp, we record Raman images originating from the carbon-carbon double bond stretch vibrations of lutein and zeaxanthin, the carotenoids comprising human macular pigments. Our Raman images reveal significnt differences among subjects, both in regard to absolute levels ss well as spatial distribution within the macula. Since the light levels used to obtain these images are well below established ssafety limits, this technique holds promise for developing a rapid screening diagnostic in large populations at risk for vision loss from age-realted macular degeneration.
Gellermann, Werner; Ermakov, Igor V.; McClane, Robert W.
Interest in macular pigment has been growing since it was first identified 200 years ago. Because of its antioxidant properties and putative protection against age-related macular degeneration (AMD), clinical, experimental, and epidemiologic studies have attempted to show a positive correlation between the high density of macular pigment and low risk for macular degeneration. Since the two main components of macular pigment, lutein and zeaxanthin, cannot be endogenously synthesized, oral supplementation may be an efficient means to increase macular pigment density. However, the ideal dosage for such supplementation remains to be determined, since absorption varies greatly from one subject to another. Hence, reliable quantitative measurement of macular pigment density is necessary before any beneficial effects of oral supplementation on AMD occurrence can be demonstrated; then at-risk subjects who would require such supplementation can be targeted. Several techniques can be used to measure macular pigment density noninvasively in vivo. Psychophysical methods are the most commonly used. They include heterochromatic flicker photometry and Raman spectroscopy. Heterochromatic flicker is the most widely used method and seems to be the easiest and least costly. However, because it requires very good cooperation from patients and a good grasp of the instructions, it is probably the least reliable and reproducible method. Raman spectroscopy, on the other hand, requires less cooperation on the part of the patient. Subjects are asked to overlap a blue disc and a red polka-dot pattern to ensure proper alignment of the eye. Since these instructions are simpler than those for heterochromatic flicker photometry, this technique is more reliable. Overall, the data obtained are more objective because they are based on the analysis of a signal emitted after an argon laser excitation of the macular pigment. Nevertheless, data are closely related to pupil diameter. Finally Raman spectroscopy requires expensive equipment. Physical methods are based on retinal excitation by an incident light and the analysis of the reflected signal obtained. These methods are mainly represented by autofluorescence measurement and fundus reflectance. These two techniques differ in the wavelength used in the incident light, because the reflected signal is itself related to the amount of incident light absorbed by retinal structures. Both techniques allow rapid and objective measurement of spatial distribution of macular pigment. The software of the modified Scanning Laser Ophthalmoscope (Heidelberg, Germany) further creates a density map image after digital subtraction of the log reflectance data obtained at two different wavelengths. Physical methods require little cooperation from patients and could be considered the most objective and high-performance technique available today. However, the instruments are still expensive and therefore cannot be widely used in clinical practice. PMID:18563047
Rougier, M B; Delyfer, M N; Korobelnik, J F
Purpose. The retinal carotenoids lutein (L) and zeaxanthin (Z) that form the macular pigment (MP) may help to prevent neovascular age-related macular degeneration. The purpose of this study was to determine whether MP density in the retina could be raised by increasing dietary intake of L and Z from foods. Methods. Macular pigment was measured psychophysically for 13 subjects. Serum
Billy R. Hammond; Elizabeth J. Johnson; Robert M. Russell; Norman I. Krinsky; Kyungjin Yeum; Ross B. Edwards; D. Max Snodderly
The spatial density distribution of macular pigment in primate retinas was described by two-wavelength microdensitometry of retinal sections. The macular pigment is most dense along the path of the receptor axons in the center of the fovea. Another band of high density is present in the inner plexiform layer in many retinas. The density in both fiber layers declines to low, relatively constant levels within 1 mm eccentricity. Both the total retinal density of macular pigment and the contributions of subsets of the retinal layers were estimated by integrating along the path of light traversing the retina from the vitreal surface to the outer segments. The integrated densities were measured at several eccentricities to establish the profile of macular pigment density along a diameter through the fovea. The macular pigment profile was unimodal in some cases and trimodal in others. The main central peak always occurred in the center of the fovea. The total retinal density of the central peak ranged from 0.42-1.0 absorbance. Most of the pigment is interposed between the outer segments and the stimulating light and is effective as a visual filter. The macular pigment is dichroic, with the major axis of absorption oriented tangential to a circle centered on the fovea. This is consistent with commonly accepted explanations of Haidinger 's brushes. PMID:6724837
Snodderly, D M; Auran, J D; Delori, F C
The macular pigments (MP) absorb light in the blue-green region of the visible spectrum and comprise two carotenoids, lutein and zeaxanthin. In humans the concentration of MP varies widely across the normal population. There are two (not mutually exclusive) proposed roles for MP: to improve visual function and to act as an antioxidant and protect the macula from damage by
Nigel P. Davies; Antony B. Morland
Three dietary carotenoids, lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ) accumulate at the central retina (macula), where they are collectively referred to as macular pigment (MP). MP’s pre-receptoral absorption of blue light and consequential attenuation of the effects of chromatic aberration and light scatter are important for optimal visual function. Furthermore, antioxidant activity of MP’s constituent carotenoids and the same blue light-filtering properties underlie the rationale for its putative protective role for age-related macular degeneration (AMD). Supplementation with L, Z and MZ augments MP and enhances visual performance in diseased and non-diseased eyes, and may reduce risk of AMD development and/or progression.
Loskutova, Ekaterina; Nolan, John; Howard, Alan; Beatty, Stephen
We built a new macular pigment reflectometer (MPR) for fast and objective measuring of the optical density of macular pigment in the human eye, using the undilated eye. The design is based on the spectral reflectance from a spot of white light at the fovea. To evaluate its performance, we measured the macular pigment of 20 healthy subjects, ages 18 to 79 years, under four conditions: (1) natural pupil in the dark, (2) natural pupil with dim room light, (3) dilated pupil in the dark, and for comparison with a different technique, (4) heterochromatic flicker photometry (HFP) in dim room light with natural pupil. Condition 1 was repeated in a subset of 10 subjects after an interval of at least 3 days. Data analysis with a model of reflectors and absorbers in the eye provided the density of the macular pigment in conditions 1 to 3. Dim room light and pupil dilatation had no influence on measured density. Mean within subjects variation was typically 7%. Mean difference between test and retest after at least 3 days was 1%. Correlation between MPR and HFP was r=0.56 (p=0.012). Mean within subjects variation with HFP was 19%. The new instrument holds promise for specific applications such as epidemiological research. PMID:17212554
van de Kraats, Jan; Berendschot, Tos T J M; Valen, Suze; van Norren, Dirk
We present a case of an otherwise healthy 10-year-old girl who presented with asymptomatic brown macules over the trunk and proximal extremities, of three months' duration. The cutaneous examination revealed multiple, dark brown, discrete, round to oval macules and a few mildly elevated lesions over the trunk and proximal limbs. The individual lesion was 1-3 cm in diameter and a few showed velvety appearance over the surface. Darier's sign was negative. The histopathological study from the velvety lesion showed acanthosis, papillomatosis and increased melanin in the basal layer. The upper dermis showed sparse perivascular infiltrate of lymphocytes without any dermal melanophages. It fulfilled the criteria for idiopathic eruptive macular pigmentation with additional histological finding of papillomatosis. PMID:23130237
Verma, Shikha; Thakur, Binod Kumar
We present a case of an otherwise healthy 10-year-old girl who presented with asymptomatic brown macules over the trunk and proximal extremities, of three months’ duration. The cutaneous examination revealed multiple, dark brown, discrete, round to oval macules and a few mildly elevated lesions over the trunk and proximal limbs. The individual lesion was 1-3 cm in diameter and a few showed velvety appearance over the surface. Darier's sign was negative. The histopathological study from the velvety lesion showed acanthosis, papillomatosis and increased melanin in the basal layer. The upper dermis showed sparse perivascular infiltrate of lymphocytes without any dermal melanophages. It fulfilled the criteria for idiopathic eruptive macular pigmentation with additional histological finding of papillomatosis.
Verma, Shikha; Thakur, Binod Kumar
Recently, a unique distribution, namely a reduction of macular pigment optical density (MPOD) within the central retina with a surrounding ring-like structure of preserved MPOD at about 6 degrees eccentricity was suggested to be a common finding in macular telangiectasia (MacTel) type 2. In order to quantify this reduced MPOD, 28 eyes of 14 patients with MacTel type 2 were
Peter Charbel Issa; Rob L. P. van der Veen; Astrid Stijfs; Frank G. Holz; Hendrik P. N. Scholl; Tos T. J. M. Berendschot
There is increasing recognition that the optical and antioxidant properties of the xanthophyll carotenoids lutein and zeaxanthin play an important role in maintaining the health and function of the human macula. In this review article, we assess the value of non-invasive quantification of macular pigment levels and distributions to identify individuals potentially at risk for visual disability or catastrophic vision loss from age-related macular degeneration, and we consider the strengths and weaknesses of the diverse measurement methods currently available.
Bernstein, Paul S.; Delori, Francois C.; Richer, Stuart; van Kuijk, Frederik J. M.; Wenzel, Adam J.
Raman detection of macular pigments (MP) holds promise as a novel noninvasive technology for the quantification of lutein and zeaxanthin carotenoids, which are thought to prevent or delay the onset of age-related macular degeneration. Using resonant excitation in the visible, we measure the Raman signals that originate from the double-bond stretch vibrations of the p-conjugated carotenoid molecule's carbon backbone. In this paper we describe the construction and performance of a new, compact, and low-cost MP Raman instrument using dielectric, angle-tuned band-pass filters for wavelength selection and single-channel photo-multiplier detection of carotenoid Raman responses. MP concentration measurements are fast and accurate, as seen in experiments with model eyes and living human eyes. The ease and rapidity of Raman MP measurements, the relative simplicity of the instrumentation, the high accuracy of the measurements, and the lack of significant systematic errors should make this technology useful for widespread clinical research.
Ermakov, Igor V.; Ermakova, Maia R.; Gellermann, Werner
BACKGROUND: Age-related macular degeneration (AMD) is a disease with multiple risk factors, many of which appear to involve oxidative stress. Macular pigment, with its antioxidant and light-screening properties, is thought to be protective against AMD. A result has been the appearance of dietary supplements containing the macular carotenoids, lutein and zeaxanthin. More recently, a supplement has been marketed containing, in
Richard A Bone; John T Landrum; Yisi Cao; Alan N Howard; Francesca Alvarez-Calderon
A low density of macular pigment may represent a risk factor for age-related macular degeneration (AMD) by permitting greater blue light damage. This study was carried out to determine the effects on macular pigment optical density of dietary supplementation with lutein, one of the pigment constituents. Two subjects consumed lutein esters, equivalent to 30 mg of free lutein per day,
JOHN T LANDRUM; RICHARD A BONE; HILDA JOA; MARK D KILBURN; LINDA L MOORE; KATHLEEN E SPRAGUE
Background Several lines of evidence suggest that macular pigment may play a protective role against age-related macular degeneration, but the influence of age on macular pigment density levels remains unclear. This study was designed to investigate the relationship between age and the normal distribution of macular pigment optical density (MPOD) values surrounding the fovea. Methods Consecutive healthy subjects with no evidence of ocular disease were enrolled in this study. After inclusion, MPOD values were measured at specific eccentricities (0.5, 1, and 2 degrees) from the foveal center using a dual-wavelength autofluorescence method employing a modified confocal scanning laser ophthalmoscope. Whenever both eyes were eligible, one was randomly selected for analysis. The correlation between age and MPOD values was investigated using regression analysis. Results Thirty subjects (30 eyes) were included (mean age 48.6 ± 16.4 [range 23–77] years). Significant differences were found between MPOD values measured at 0.5, 1, and 2 degrees from the center of the fovea (0.49 ± 0.12 density units, 0.37 ± 0.11 density units, and 0.13 ± 0.05 density units, respectively, P < 0.05). Significant correlations between age and MPOD values at 0.5 and 1 degree were found (P ? 0.02). Values measured at 2 degrees did not correlate significantly with age (P = 0.06). Conclusion In healthy subjects, MPOD values were highest near the foveal center. These values appeared to increase during adulthood (peak at 45–50 years), followed by a gradual reduction after 60 years of age.
Lima, Veronica Castro; Rosen, Richard B; Prata, Tiago Santos; Dorairaj, Syril; Spielberg, Leigh; Maia, Mauricio; Sallum, Juliana M
Purpose To evaluate the application of 488 and 514?nm fundus autofluorescence (FAF) and macular pigment optical density (MPOD) imaging in diabetic macular oedema (DMO) and to demonstrate the typical imaging features. Patients and Methods A hundred and twenty-five eyes of 71 consecutive patients with diabetic retinopathy who underwent examination at a specialist university clinic employing a modified Heidelberg Retina Angiograph, using two different light sources of 488 and 514?nm wavelength, were retrospectively reviewed. MPOD images were calculated using modified Heidelberg Eye Explorer software. All images were evaluated by two independent masked graders. Features from FAF and MPOD images were correlated with optical coherence tomography (OCT) imaging findings and inter-grader variability, sensitivity and specificity were calculated using OCT as reference. Results Sixty-seven eyes had DMO on OCT. The inter-grader variability was 0.84 for 488?nm FAF, 0.63 for 514?nm FAF and 0.79 for MPOD imaging. Sensitivity and specificity for detection of DMO were 80.6 and 89.7% for 488?nm FAF; 55.2 and 94.8% for 514?nm FAF; and 80.6 and 91.4% for MPOD imaging. In 488?nm FAF and MPOD imaging, DMO was better visualised in comparison with 514?nm FAF imaging, P<0.01. MPOD revealed displacement of macular pigment by intraretinal cysts. Conclusion MPOD imaging, and particularly its combination with 488?nm and 514?nm FAF, provides a valuable addition to OCT in the evaluation of DMO and is clinically useful in rapid en-face assessment of the central macula.
Waldstein, S M; Hickey, D; Mahmud, I; Kiire, C A; Charbel Issa, P; Chong, N V
Purpose: The 3 carotenoids lutein, zeaxanthin, and meso-zeaxanthin, which account for the ‘yellow spot’ at the macula and which are referred to as macular pigment (MP), are believed to play a role in visual function and protect against age-related macular degeneration (AMD) via their optical and antioxidant properties. This study was undertaken to compare MP optical density (MPOD) in a
John M. Nolan; Roseanne Kenny; Claire O’Regan; Hilary Cronin; James Loughman; Eithne E. Connolly; Patricia Kearney; Edward Loane; Stephen Beatty
Recently, a unique distribution, namely a reduction of macular pigment optical density (MPOD) within the central retina with a surrounding ring-like structure of preserved MPOD at about 6 degrees eccentricity was suggested to be a common finding in macular telangiectasia (MacTel) type 2. In order to quantify this reduced MPOD, 28 eyes of 14 patients with MacTel type 2 were investigated by fundus reflectometry and two wavelengths fundus autofluorescence (FAF; at 488 nm and 514 nm). Fundus reflectometry showed a reduced MPOD within the central 4 degrees eccentricity that was most absent temporal to the foveola. At 6 degrees, MP density was not different from normative values. Two wavelengths FAF was in accordance with these findings. Fundus reflectometry also allowed separate determination of lutein and zeaxanthin. The patients with MacTel type 2 showed a disproportionally high zeaxanthin reduction. The study suggests that in MacTel type 2, there might be an inability to accumulate MP in the central retina. This disease might serve as a model to further study abnormalities of MP distribution in retinal disorders and to elucidate the mechanisms of MP deposition in the retina. PMID:19233170
Charbel Issa, Peter; van der Veen, Rob L P; Stijfs, Astrid; Holz, Frank G; Scholl, Hendrik P N; Berendschot, Tos T J M
Background Macular pigment has been the focus of much attention in recent years, as a potential modifiable risk factor for age-related\\u000a macular degeneration. This interest has been heightened by the ability to measure macular pigment optical density (MPOD) in\\u000a vivo.\\u000a \\u000a \\u000a \\u000a \\u000a Method A systematic literature search was undertaken to identify all available papers that have used in vivo MPOD techniques. The\\u000a papers were
Olivia Howells; Frank Eperjesi; Hannah Bartlett
Objectives The objectives of this study were to report peculiar postoperative changes at the level of the retinal pigment epithelium (RPE) in young women with moderate or mild myopia and classic choroidal neovascularisation first treated unsuccessfully with photodynamic therapy (PDT) and afterwards with limited macular translocation.Methods Retrospective review of two young myopic women who underwent PDT for treatment of idiopathic choroidal neovascularisation.
Agnčs Glacet-Bernard; Gabriel Coscas; Gisčle Soubrane
BackgroundTo determine long-term functional and morphological changes after full macular translocation (FMT) with 360° retinotomy in patients with retinal pigment epithelium (RPE) tears, in light of the increasing number of reports of this complication following vascular endothelial growth factor (VEGF)-modulating therapy.MethodsWe retrospectively reviewed a consecutive series of six patients with RPE tears secondary to neovascular age-related macular degeneration who underwent
A. Polito; M. Cereda; F. Romanelli; G. Pertile
The measurement of macular pigment optical density (MPOD) in the eye is often carried out using optical techniques based on heterochromatic flicker photometry (HFP). These require the use of two spectrally-narrow beams, one at the wavelength of maximum absorption of the macular pigment (MP) and the other in the long wavelength region of the visible spectrum where MP absorption is negligible. A new technique for the measurement of MPOD spatial profiles has been developed by overcoming the current shortcomings associated with the use of visual displays. The new Macular Assessment Profile (MAP) test makes use of a 'notch' filter and a photometric model to measure and compute the peak MPOD value. Two other useful parameters are also computed from the same measurements. These describe the subject's sensitivity to rapid flicker and the absorption of blue light by the lens. MPOD profiles, lens density, rapid flicker sensitivity, and red/green (RG) and yellow/blue (YB) colour thresholds were measured in 54 normal subjects aged 18-61 years. The results confirm previous findings on ageing effects and demonstrate the complete absence of correlation between MPOD and the subject's YB chromatic thresholds. In contrast, RG chromatic sensitivity improves with higher levels of MPOD. PMID:20883330
Barbur, J L; Konstantakopoulou, E; Rodriguez-Carmona, M; Harlow, J A; Robson, A G; Moreland, J D
To report two cases of full-thickness macular hole (FTMH) formation associated with pigment epithelial detachment (PED). Two patients presenting with visual loss and metamorphopsia were evaluated with fundal fluorescein angiography (FFA) and optical coherence tomography (OCT). Case 1: Fundus examination and FFA revealed a small subfoveal PED. Subsequent serial OCT elucidated the progressive formation of a FTMH. Case 2: Fundus examination and FFA revealed a small PED and changes suggestive of central serous retinopathy (CSR). Subsequent OCT illustrated a FTMH with an underlying small PED at the base of the hole. It is possible that, in at least some cases of macular hole formation, there may be a causative link with PED. To my knowledge, this is the first report of full-thickness macular hole formation associated with pigment epithelial detachment. PMID:20517636
Purpose: To analyze and compare the angiographic features of retinal vascular anomalous complex (RVAC) in patients with a vascularized pigment epithelial detachment (PED) secondary to age-related macular degeneration. Methods: Retrospective evaluation of fluorescein and indocyanine green angiographies of 180 patients with occult choroidal neovascularization and PED. Results: On indocyanine green angiography (ICGA), RVAC demonstrated as a focal hyperfluorescence in connection
Ulrike Schneider; Faik Gelisken; Werner Inhoffen; Karl Ulrich Bartz-Schmidt
PURPOSE. Lutein (L) and zeaxanthin (Z) are two dietary carote- noids that accumulate at the macula, where they are collec- tively known as macular pigment (MP). There is a biologically plausible rationale, with some supporting evidence, that MP may protect against age-related maculopathy (ARM). This study was undertaken to investigate the relationship between dietary intake of L and Z, serum
John M. Nolan; Jim Stack; Eamonn O'Connell; Stephen Beatty
A new simple method for two-dimensional determination of optical density of macular pigment xanthophyll (ODx) in clinical routine is based on a single blue-reflection fundus image. Individual different vignetting is corrected by a shading function. For its construction, nodes are automatically found in structureless image regions. The influence of stray light in elderly crystalline lenses is compensated by a correction
Dietrich Schweitzer; Susanne Jentsch; Jens Dawczynski; Martin Hammer; Ute E. K. Wolf-Schnurrbusch; Sebastian Wolf
Age-related macular degeneration (AMD) is the leading cause of severe visual impairment in the elderly in developed countries. AMD patients have ele- vated levels of iron within the retinal pigment epithelia (RPE), which may lead to oxidative damage to mitochon- dria, disruption of retinal metabolism, and vision impair- ment or loss. As a possible model for iron-induced AMD, we investigated
Ludmila A. Voloboueva; David W. Killilea; Hani Atamna; Bruce N. Ames
Purpose. Age-Related Eye Disease Study 2 (AREDS2) is a randomized, placebo-controlled study designed to determine whether supplementation with 10 mg of lutein and 2 mg of zeaxanthin per day can slow the rate of progression of age-related macular degeneration (AMD). Although some biomarkers of response to carotenoid supplementation such as serum concentrations are part of the AREDS2 protocol, measurement of carotenoid concentrations in the eye and other tissues is not. In this approved ancillary study, macular pigment optical density (MPOD), macular pigment distributions, and skin carotenoid levels at enrollment and at each annual visit were measured to assess baseline carotenoid status and to monitor response to assigned interventions. Methods. All subjects enrolled at the Moran Eye Center had MPOD and macular pigment spatial distributions measured by dual-wavelength autofluorescence imaging and total skin carotenoids measured by resonance Raman spectroscopy. Results. Baseline MPOD in enrolled subjects was unusually high relative to an age-matched control group that did not consume carotenoid supplements regularly, consistent with the high rate of habitual lutein and zeaxanthin consumption in Utah AREDS2 subjects prior to enrollment. MPOD did not correlate with serum or skin carotenoid measurements. Conclusions. Useful information is provided through this ancillary study on the ocular carotenoid status of AREDS2 participants in the target tissue of lutein and zeaxanthin supplementation: The macula. When treatment assignments are unmasked at the conclusion of the study, unique tissue-based insights will be provided on the progression of AMD in response to long-term, high-dose carotenoid supplementation versus diet alone. (ClinicalTrials.gov number, NCT00345176.)
Bernstein, Paul S.; Ahmed, Faisal; Liu, Aihua; Allman, Susan; Sheng, Xiaoming; Sharifzadeh, Mohsen; Ermakov, Igor; Gellermann, Werner
PURPOSE. To determine macular pigment (MP) optical density (OD) in patients with ABCA4-associated retinal degenerations (ABCA4-RD) and the response of MP and vision to supplemen- tation with lutein. METHODS. Patients with Stargardt disease or cone-rod dys- trophy and known or suspected disease-causing mutations in the ABCA4 gene were included. All patients had foveal fixation. MPOD profiles were measured with heterochro-
Tomas S. Aleman; Artur V. Cideciyan; Elizabeth A. M. Windsor; Sharon B. Schwartz; Malgorzata Swider; John D. Chico; Alexander Sumaroka; Alexander Y. Pantelyat; Keith G. Duncan; Leigh M. Gardner; Jessica M. Emmons; Janet D. Steinberg; Edwin M. Stone; Samuel G. Jacobson
We report an unusual case of primary dystrophy of the retinal pigment epithelium (RPE) in which a vitelliform macular appearance was associated with reticular hyperpigmentation resembling the pattern dystrophies of the RPE. The entire evolution of the disease was observed and documented step-by-step during a 10-year follow-up. During the progressive change of the lesions morphologic characteristics of butterfly, reticular and
F. Cardillo Piccolino; M. Zingirian
Choroidal new vessel (CNV) excision may improve vision in patients with age-related macular degeneration (AMD) by eliminating\\u000a the source of subretinal bleeding and scarring. Visual recovery after CNV excision is usually poor in AMD patients, probably\\u000a because of removal of the associated retinal pigment epithelium (RPE), coupled with the inability of native RPE at the edge\\u000a of the dissection bed
Ilene K. Sugino; Hao Wang; Marco A. Zarbin
Lutein and zeaxanthin, two oxygenated carotenoids, exclusively accumulate in the macula, protecting the underlying photoreceptors and retinal pigment epithelial cells from damaging blue radiation of sunlight. As macular pigment, lutein and zeaxanthin are also potent antioxidants protecting the vulnerable regions of retina from free radical injury. Oxidative stress and cumulative light damage play an important role in pathogenesis of age-related
The study was undertaken to answer the question that how many patients with pigmentation of back and arms actually have amyloid deposits in pathology. 44 patients presenting with diffuse pigmentation of back and arms (DPOBA) were selected. Skin biopsies were performed in all cases from the affected sites. On all formalin fixed and paraffin embedded specimens, the following histochemical stains were performed: Haematoxylin and eosin (H&E), Congo red and immunohistochemical staining using anti-cytokeratin monoclonal antibody. In 9 of 44 cases (20%), amyloid deposits were found. In the remaining 35 cases (80%), H&E, Congo red and immunohistochemical staining failed to show any amyloid deposition. We were unable to find amyloid deposition in most of the patients presented with DPOBA. It seems that the signs may be attributable other disorders with similar clinical but different pathophysiologic aspects. PMID:23737318
Ghodsi, Seyed Zahra; Rahimi, Pari; Ehsani, Amir; Noormohammadpour, Pedram; Asgrai, Masood; Gholamali, Fatemeh
Two carotenoids found in egg yolk, lutein and zeaxanthin, accumulate in the macular retina where they may reduce photostress. Increases in serum lutein and zeaxanthin were observed in previous egg interventions, but no study measured macular carotenoids. The objective of this project was to determine whether increased consumption of eggs would increase retinal lutein and zeaxanthin, or macular pigment. Twenty-four females, between 24 and 59 y, were assigned to a pill treatment (PILL) or 1 of 2 egg treatments for 12 wk. Individuals in the PILL treatment consumed 1 sugar-filled capsule/d. Individuals in the egg treatments consumed 6 eggs/wk, containing either 331 microg (EGG 1) or 964 microg (EGG 2) of lutein and zeaxanthin/yolk. Serum cholesterol, serum carotenoids, and macular pigment OD (MPOD) were measured at baseline and after 4, 8, and 12 wk of intervention. Serum cholesterol concentrations did not change in either egg treatment group, but total cholesterol (P = 0.04) and triglycerides (P = 0.02) increased in the PILL group. Serum zeaxanthin, but not serum lutein, increased in both the EGG 1 (P = 0.04) and EGG 2 (P = 0.01) groups. Likewise, MPOD increased in both the EGG 1 (P = 0.001) and EGG 2 (P = 0.049) groups. Although the aggregate concentration of carotenoid in 1 egg yolk may be modest relative to other sources, such as spinach, their bioavailability to the retina appears to be high. Increasing egg consumption to 6 eggs/wk may be an effective method to increase MPOD. PMID:16988128
Wenzel, Adam J; Gerweck, Catherine; Barbato, Damian; Nicolosi, Robert J; Handelman, Garry J; Curran-Celentano, Joanne
Background We investigated whether pigment epithelium-derived factor (PEDF) or vascular endothelial growth factor (VEGF) influence macular\\u000a edema in patients with branch retinal vein occlusion (BRVO). This investigation aimed to clarify the influence of PEDF in\\u000a the vitreous fluid on retinal vascular permeability in patients with macular edema secondary to BRVO. The findings were expected\\u000a to be useful for the treatment of
Hidetaka Noma; Hideharu Funatsu; Tatsuya Mimura; Seiyo Harino; Shuichiro Eguchi; Sadao Hori
Age-related macular degeneration (AMD) is attributed to a complex interaction of genetic and environmental factors. It is characterized by degeneration involving the retinal photoreceptors, retinal pigment epithelium (RPE) and Bruch's membrane, as well as alterations in choroidal capillaries. AMD pathogenesis is strongly associated with chronic oxidative stress and inflammation that ultimately lead to protein damage, aggregation and degeneration of RPE. Specific degenerative findings for AMD are accumulation of intracellular lysosomal lipofuscin and extracellular drusens. In this review, we discuss thoroughly RPE-derived mechanisms in AMD pathology. PMID:22112056
Kinnunen, Kati; Petrovski, Goran; Moe, Morten C; Berta, András; Kaarniranta, Kai
A comparison of macular pigment optical density (MPOD) spatial profiles determined by an optical and a psychophysical technique is presented. We measured the right eyes of 19 healthy individuals, using fundus reflectometry at 0, 1, 2, 4, 6, and 8 deg eccentricity; and heterochromatic flicker photometry (HFP) at 0, 0.5, 1, 2, 3, 4, 5, 6, and 7 deg, and
Rob L. P. van der Veen; Tos T. J. M. Berendschot; Maria Makridaki; Fred Hendrikse; David Carden; Ian J. Murray
Accumulation of vitamin A-derived lipofuscin fluorophores in the retinal pigment epithelium (RPE) is a pathologic feature of recessive Stargardt macular dystrophy, a blinding disease caused by dysfunction or loss of the ABCA4 transporter in rods and cones. Age-related macular degeneration, a prevalent blinding disease of the elderly, is strongly associated with mutations in the genes for complement regulatory proteins (CRP), causing chronic inflammation of the RPE. Here we explore the possible relationship between lipofuscin accumulation and complement activation in vivo. Using the abca4(-/-) mouse model for recessive Stargardt, we investigated the role of lipofuscin fluorophores (A2E-lipofuscin) on oxidative stress and complement activation. We observed higher expression of oxidative-stress genes and elevated products of lipid peroxidation in eyes from abca4(-/-) versus wild-type mice. We also observed higher levels of complement-activation products in abca4(-/-) RPE cells. Unexpectedly, expression of multiple CRPs, which protect cells from attack by the complement system, were lower in abca4(-/-) versus wild-type RPE. To test whether acute exposure of healthy RPE cells to A2E-lipofuscin affects oxidative stress and expression of CRPs, we fed cultured fetal-derived human RPE cells with rod outer segments from wild-type or abca4(-/-) retinas. In contrast to RPE cells in abca4(-/-) mice, human RPE cells exposed to abca4(-/-) rod outer segments adaptively increased expression of both oxidative-stress and CRP genes. These results suggest that A2E accumulation causes oxidative stress, complement activation, and down-regulation of protective CRP in the Stargardt mouse model. Thus, Stargardt disease and age-related macular degeneration may both be caused by chronic inflammation of the RPE. PMID:21464132
Radu, Roxana A; Hu, Jane; Yuan, Quan; Welch, Darcy L; Makshanoff, Jacob; Lloyd, Marcia; McMullen, Stephen; Travis, Gabriel H; Bok, Dean
BACKGROUND—Subthreshold (retinal pigment epithelium) photocoagulation is a new photocoagulation method, which treats the retinal pigment epithelium (RPE) and avoids damage to the neural retina. The initial results in this prospective pilot study on various macular diseases are presented.?METHODS—12 patients with diabetic maculopathy (group I), 10 with soft drusen (group II), and four with central serous retinopathy (CSR) (group III) were treated and followed up for 1 year. Treatment was achieved using a train of repetitive short laser pulses (1.7 µs) of a green Nd:YLF laser (parameters: 527 nm, 100 and 500 pulses, repetition rate: 500 Hz, spot size: 160 µm, energies: 70-100 µJ). Laser energy was based on the visibility of test lesions on fluorescein angiography (50-130 µJ). Patients were examined at various times by ophthalmoscopy, fluorescein and ICG angiography, and infrared imaging.?RESULTS—After 6 months hard exudates disappeared in six out of nine patients in group I and leakage disappeared in six out of 12 diabetic patients. In group II drusen were less in seven out of 10 patients. In group III serous detachment disappeared in three out of four cases. Visual acuity was stable in all cases. None of the laser lesions was clinically visible immediately. After 1 day most lesions were visible as yellowish RPE depigmentation. After 3 months some of the lesions were visible as hyperpigmented areas but most were not. Fluorescein angiography showed leakage only in the first week. Infrared imaging showed that most lesions can be visualised in groups I and II after a period longer than 1 week as hyperreflective areas.?CONCLUSION—This study showed that subthreshold (RPE) photocoagulation is effective in some cases of diabetic maculopathy, drusens, and in CSR. Visibility of laser burns is not always necessary in the treatment of macular diseases presented here. Infrared imaging is an effective and non-invasive way of visualising subthreshold (RPE) laser burns.??
Roider, J.; Brinkmann, R.; Wirbelauer, C.; Laqua, H.; Birngruber, R.
OBJECTIVES To determine whether there is a difference in neuroretinal function and in macular pigment optical density between persons with high- and low-risk gene variants for age-related macular degeneration (AMD) and no ophthalmoscopic signs of AMD, and to compare the results on neuroretinal function to patients with manifest early AMD. METHODS Neuroretinal function was assessed with the multifocal electroretinogram for 32 participants (22 healthy persons with no AMD and 10 patients with early AMD). The 22 healthy participants with no AMD had either high- or low-risk genotypes for CFH (rs380390) and/or ARMS2 (rs10490924). Trough-to-peak response densities and peak-implicit times were analyzed in 5 concentric rings. Macular pigment optical density was assessed by use of customized heterochromatic flicker photometry. RESULTS Trough-to-peak response densities for concentric rings 1 to 3 were, on average, significantly greater in participants with high-risk genotypes than in participants with low-risk genotypes and in persons with early AMD after correction for age and smoking (P < .05). The group peak-implicit times for ring 1 were, on average, delayed in the patients with early AMD compared with the participants with high- or low-risk genotypes, although these differences were not significant. There was no significant correlation between genotypes and macular pigment optical density. CONCLUSIONS Increased neuroretinal activity in persons who carry high-risk AMD genotypes may be due to genetically determined subclinical inflammatory and/or histological changes in the retina. Neuroretinal function in healthy persons genetically susceptible to AMD may be a useful additional early biomarker (in combination with genetics) of AMD before there is a clinical manifestation. PMID:22777494
Feigl, Beatrix; Morris, C Phillip; Brown, Brian; Zele, Andrew J
We report a case of progressive atrophy of the retinal pigment epithelium (RPE) after trypan-blue-assisted peeling of internal limiting membrane (ILM) for macular hole surgery. A 68-year-old Caucasian female underwent a 20-g pars plana vitrectomy for a chronic stage-3 macular hole. The ILM was stained with 0.06% trypan blue (VisionBlue™, DORC Netherlands) for 2 min after fluid air exchange. Dye was reapplied for another 2 min due to poor staining. The ILM was completely removed around the macular hole with forceps. RPE atrophy was noticed at the edge of the hole 1 month after surgery. It progressively increased in intensity and enlarged over 2 years. Her final visual acuity was counting fingers, significantly worse compared to her presenting visual acuity of 20/200. Progressive atrophy of RPE in our patient was most likely due to the toxicity of trypan blue. Reapplication of the dye may increase the likelihood of toxicity.
Jain, Sachin; Kishore, Kamal; Sharma, Yog Raj
A new simple method for two-dimensional determination of optical density of macular pigment xanthophyll (ODx) in clinical routine is based on a single blue-reflection fundus image. Individual different vignetting is corrected by a shading function. For its construction, nodes are automatically found in structureless image regions. The influence of stray light in elderly crystalline lenses is compensated by a correction function that depends on age. The reproducibility of parameters in a one-wavelength reflection method determined for three subjects (47, 61, and 78 years old) was: maxODx = 6.3%, meanODx = 4.6%, volume = 6%, and area = 6% already before stray-light correction. ODx was comparable in pseudophakic and in an eye with a crystalline lens of the same 11 subjects after stray-light correction. Significant correlation in ODx was found between the one-wavelength reflection method and the two-wavelength autofluorescence method for pseudophakic and cataract eyes of 19 patients suffering from dry age-related macular degeneration (AMD) (R(2) = 0.855). In pseudophakic eyes, maxODx was significantly lower for dry AMD (n = 45) (ODx = 0.491±0.102 ODU) than in eyes with healthy fundus (n = 22) (ODx = 0.615±0.103 ODU) (p = 0.000033). Also in eyes with crystalline lens, maxODx was lower in AMD (n = 125) (ODx = 0.610±0.093 ODU) than in healthy subjects (n = 45) (ODx = 0.674±0.098 ODU) (p = 0.00019). No dependence on age was found in the pseudophakic eyes both of healthy subjects and AMD patients. PMID:21198162
Schweitzer, Dietrich; Jentsch, Susanne; Dawczynski, Jens; Hammer, Martin; Wolf-Schnurrbusch, Ute E K; Wolf, Sebastian
We investigated the feasibility of a novel method for hyperspectral mapping of macular pigment (MP) in vivo. Six healthy subjects were recruited for noninvasive imaging using a snapshot hyperspectral system. The three-dimensional full spatial-spectral data cube was analyzed using non-negative matrix factorization (NMF), wherein the data was decomposed to give spectral signatures and spatial distribution, in search for the MP absorbance spectrum. The NMF was initialized with the in vitro MP spectrum and rank 4 spectral signature decomposition was used to recover the MP spectrum and optical density in vivo. The recovered MP spectra showed two peaks in the blue spectrum, characteristic of MP, giving a detailed in vivo demonstration of these absorbance peaks. The peak MP optical densities ranged from 0.08 to 0.22 (mean 0.15+/-0.05) and became spatially negligible at diameters 1100 to 1760 ?m (4 to 6 deg) in the normal subjects. This objective method was able to exploit prior knowledge (the in vitro MP spectrum) in order to extract an accurate in vivo spectral analysis and full MP spatial profile, while separating the MP spectra from other ocular absorbers. Snapshot hyperspectral imaging in combination with advanced mathematical analysis provides a simple cost-effective approach for MP mapping in vivo.
Fawzi, Amani A.; Lee, Noah; Acton, Jennifer H.; Laine, Andrew F.; Smith, R. Theodore
PURPOSE To examine changes of select reduction-oxidation (redox) sensitive proteins from human donor retinal pigment epithelium (RPE) at four stages of age-related macular degeneration (AMD). DESIGN Experimental study. METHODS Human donor eyes were obtained from the Minnesota Lions Eye Bank and graded using the Minnesota Grading System (MGS) into four stages that correspond to stages defined by the age-related eye disease study (AREDS). Protein content in RPE homogenates was measured using Western immunoblotting with protein-specific antibodies. RESULTS The content of several antioxidant enzymes and specific proteins that facilitate refolding or degradation of oxidatively damaged proteins increased significantly in MGS stage 3. These proteins are involved in the primary (copper-zinc superoxide dismutase [CuZnSOD], manganese superoxide dismutase [MnSOD], and catalase) and secondary (heat shock protein [HSP] 27, HSP 90, and proteasome) defense against oxidative damage. Additionally, the insulin pro-survival receptor exhibited disease-related upregulation. CONCLUSIONS The pattern of protein changes identified in human donor tissue graded using the MGS support the role of oxidative mechanisms in the pathogenesis and progression of AMD. The MGS uses nearly identical clinical definitions and grading criteria of AMD that are used in the AREDS, so our results apply to clinical and epidemiologic studies using similar definitions. Results from our protein analysis of human donor tissue helps to explain altered oxidative stress regulation and cell-survival pathways that occur in progressive stages of AMD.
DECANINI, ALEJANDRA; NORDGAARD, CURTIS L.; FENG, XIAO; FERRINGTON, DEBORAH A.; OLSEN, TIMOTHY W.
PURPOSE: To describe the indications, surgical technique, and clinical results of 14 eyes in 13 patients with age-related macular degeneration and foveal choroidal neovascularization, in which subretinal surgery was combined with simultaneous transplantation of autologous retinal pigment epithelial cells.METHODS: Between March 1999 and February 2000, in a prospective study, 14 eyes (13 patients) with age-related macular degeneration underwent subretinal surgery
Susanne Binder; Ulrike Stolba; Ilse Krebs; Lukas Kellner; Christian Jahn; Hans Feichtinger; Margit Povelka; Ursula Frohner; Andreas Kruger; Ralf-Dieter Hilgers; Walter Krugluger
Malattia leventinese (ML) is a dominantly inherited macular degenerative disease characterized by the presence of sub-retinal pigment epithelium (RPE) deposits. With the exception of an earlier age of onset, ML patients exhibit symptoms and histopathology compatible with the diagnosis of age-related macular degeneration (AMD), the most common cause of incurable blindness. ML is caused by a mutation (R345W) in the
Lihua Y. Marmorstein; Precious J. McLaughlin; Neal S. Peachey; Takako Sasaki; Alan D. Marmorstein
The associations between the intake of the fat-substitute olestra and the concentrations of macular carotenoid pigments and serum lutein and zeaxanthin were investigated in a volunteer cross-sectional sample in Indianapolis. The study was conducted in January through March, 1998 after olestra-containing savory snacks had been sold in central Indiana for a year. Volunteers (n = 280) aged 18-50 y were recruited to make a single clinic visit during which macular pigment optical density (MPOD) was determined by psychophysical flicker photometry, serum was obtained for determination of lutein and zeaxanthin concentration, usual intake of olestra, carotenoids and nutrients were assessed by 1-y food frequency questionnaire, and health habits including smoking, physical characteristics such as eye color, demographics and medical history were determined by questionnaire. Intake of olestra at least one time per month for the past year was reported by 81:280 subjects and their mean, median and 90(th) percentile intakes were 1.09, 0.34 and 2.43 g olestra/d, respectively. Mean macular pigment optical density was not significantly different between olestra consumers and nonconsumers (0.213 +/- 0.014 vs. 0.211 +/- 0.010) nor was serum lutein and zeaxanthin concentration (0.361 +/- 0.017 vs. 0.375 +/- 0. 013 micromol/L) or intake (1242 +/- 103 mg/d vs. 1042 +/- 58 mg/d) in one-way or two-way ANOVA. Olestra intake was not associated with MPOD or serum lutein and zeaxanthin before or after correction for significant covariates of MPOD. Thus, olestra intake over the past year in a cross-sectional volunteer sample in Indianapolis was not associated with MPOD. PMID:10702598
Cooper, D A; Curran-Celentano, J; Ciulla, T A; Hammond, B R; Danis, R B; Pratt, L M; Riccardi, K A; Filloon, T G
Objective: To assess the prevalence of recurrence of macular geographic atrophy (GA) of the retinal pig- ment epithelium (RPE) after macular translocation with 360° retinectomy (MT360) in one institution. Methods: A retrospective review of all cases of GA that were treated with MT360 in 1 institution. Demographic and clinical data including the duration of preoperative visual loss, preoperative and postoperative
Mark T. Cahill; Prithvi Mruthyunjaya; Catherine Bowes Rickman; Cynthia A. Toth
Objective: To assess the prevalence of recurrence of macular geographic atrophy (GA) of the retinal pig- ment epithelium (RPE) after macular translocation with 360° retinectomy (MT360) in one institution. Methods: A retrospective review of all cases of GA that were treated with MT360 in 1 institution. Demographic and clinical data including the duration of preoperative visual loss, preoperative and postoperative
Mark T. Cahill; Prithvi Mruthyunjaya; Catherine Bowes Rickman; Cynthia A. Toth
Among the identified risk factors of age-related macular degeneration, sunlight is known to induce cumulative damage to the retina. A photosensitive derivative of the visual pigment, N-retinylidene-N-retinylethanolamine (A2E), may be involved in this phototoxicity. The high energy visible light between 380 nm and 500 nm (blue light) is incriminated. Our aim was to define the most toxic wavelengths in the blue-green range on an in vitro model of the disease. Primary cultures of porcine retinal pigment epithelium cells were incubated for 6 hours with different A2E concentrations and exposed for 18 hours to 10 nm illumination bands centered from 380 to 520 nm in 10 nm increments. Light irradiances were normalized with respect to the natural sunlight reaching the retina. Six hours after light exposure, cell viability, necrosis and apoptosis were assessed using the Apotox-Glo Triplex™ assay. Retinal pigment epithelium cells incubated with A2E displayed fluorescent bodies within the cytoplasm. Their absorption and emission spectra were similar to those of A2E. Exposure to 10 nm illumination bands induced a loss in cell viability with a dose dependence upon A2E concentrations. Irrespective of A2E concentration, the loss of cell viability was maximal for wavelengths from 415 to 455 nm. Cell viability decrease was correlated to an increase in cell apoptosis indicated by caspase-3/7 activities in the same spectral range. No light-elicited necrosis was measured as compared to control cells maintained in darkness. Our results defined the precise spectrum of light retinal toxicity in physiological irradiance conditions on an in vitro model of age-related macular degeneration. Surprisingly, a narrow bandwidth in blue light generated the greatest phototoxic risk to retinal pigment epithelium cells. This phototoxic spectrum may be advantageously valued in designing selective photoprotection ophthalmic filters, without disrupting essential visual and non-visual functions of the eye. PMID:24058402
Arnault, Emilie; Barrau, Coralie; Nanteau, Céline; Gondouin, Pauline; Bigot, Karine; Viénot, Françoise; Gutman, Emmanuel; Fontaine, Valérie; Villette, Thierry; Cohen-Tannoudji, Denis; Sahel, José-Alain; Picaud, Serge
Among the identified risk factors of age-related macular degeneration, sunlight is known to induce cumulative damage to the retina. A photosensitive derivative of the visual pigment, N-retinylidene-N-retinylethanolamine (A2E), may be involved in this phototoxicity. The high energy visible light between 380 nm and 500 nm (blue light) is incriminated. Our aim was to define the most toxic wavelengths in the blue-green range on an in vitro model of the disease. Primary cultures of porcine retinal pigment epithelium cells were incubated for 6 hours with different A2E concentrations and exposed for 18 hours to 10 nm illumination bands centered from 380 to 520 nm in 10 nm increments. Light irradiances were normalized with respect to the natural sunlight reaching the retina. Six hours after light exposure, cell viability, necrosis and apoptosis were assessed using the Apotox-Glo Triplex™ assay. Retinal pigment epithelium cells incubated with A2E displayed fluorescent bodies within the cytoplasm. Their absorption and emission spectra were similar to those of A2E. Exposure to 10 nm illumination bands induced a loss in cell viability with a dose dependence upon A2E concentrations. Irrespective of A2E concentration, the loss of cell viability was maximal for wavelengths from 415 to 455 nm. Cell viability decrease was correlated to an increase in cell apoptosis indicated by caspase-3/7 activities in the same spectral range. No light-elicited necrosis was measured as compared to control cells maintained in darkness. Our results defined the precise spectrum of light retinal toxicity in physiological irradiance conditions on an in vitro model of age-related macular degeneration. Surprisingly, a narrow bandwidth in blue light generated the greatest phototoxic risk to retinal pigment epithelium cells. This phototoxic spectrum may be advantageously valued in designing selective photoprotection ophthalmic filters, without disrupting essential visual and non-visual functions of the eye.
Arnault, Emilie; Barrau, Coralie; Nanteau, Celine; Gondouin, Pauline; Bigot, Karine; Vienot, Francoise; Gutman, Emmanuel; Fontaine, Valerie; Villette, Thierry; Cohen-Tannoudji, Denis; Sahel, Jose-Alain; Picaud, Serge
We report a case of progressive atrophy of the retinal pigment epithelium (RPE) after trypan-blue-assisted peeling of internal limiting membrane (ILM) for macular hole surgery. A 68-year-old Caucasian female underwent a 20-g pars plana vitrectomy for a chronic stage-3 macular hole. The ILM was stained with 0.06% trypan blue (VisionBlue™, DORC Netherlands) for 2 min after fluid air exchange. Dye was reapplied for another 2 min due to poor staining. The ILM was completely removed around the macular hole with forceps. RPE atrophy was noticed at the edge of the hole 1 month after surgery. It progressively increased in intensity and enlarged over 2 years. Her final visual acuity was counting fingers, significantly worse compared to her presenting visual acuity of 20/200. Progressive atrophy of RPE in our patient was most likely due to the toxicity of trypan blue. Reapplication of the dye may increase the likelihood of toxicity. PMID:23619488
Jain, Sachin; Kishore, Kamal; Sharma, Yog Raj
Retinal pigment epithelial (RPE) cells play a vital role in retinal physiology by forming the outer blood–retina barrier and supporting photoreceptor function. Retinopathies including age-related macular degeneration (AMD) involve physiological and pathological changes in the epithelium, severely impairing the retina and effecting vision. Nuclear receptors (NRs), including peroxisome proliferator-activated receptor and liver X receptor, have been identified as key regulators of physiological pathways such as lipid metabolic dysregulation and inflammation, pathways that may also be involved in development of AMD. However, the expression levels of NRs in RPE cells have yet to be systematically surveyed. Furthermore, cell culture lines are widely used to study the biology of RPE cells, without knowledge of the differences or similarities in NR expression and activity between these in vitro models and in vivo RPE. Using quantitative real-time PCR, we assessed the expression patterns of all 48 members of the NR family plus aryl hydrocarbon receptor and aryl hydrocarbon receptor nuclear translocator in human RPE cells. We profiled freshly isolated cells from donor eyes (in vivo), a spontaneously arising human cell line (in vitro), and primary cell culture lines (in vitro) to determine the extent to which NR expression in the cultured cell lines reflects that of in vivo. To evaluate the validity of using cell culture models for investigating NR receptor biology, we determined transcriptional activity and target gene expression of several moderately and highly expressed NRs in vitro. Finally, we identified a subset of NRs that may play an important role in pathobiology of AMD.
Dwyer, Mary A.; Kazmin, Dmitri; Hu, Peng; McDonnell, Donald P.
Pigment epithelium-derived factor (PEDF) has recently been shown to be the most potent inhibitor of angiogenesis in the mammalian eye, suggesting that loss of PEDF is involved in the pathogenesis of proliferative diabetic retinopathy. However, a protective role for PEDF in pericyte loss requires elucidation. Present studies suggest that PEDF proteins could protect against advanced glycation end product (AGE), which induce injury in retinal pericytes. Substitution of PEDF proteins may be a promising strategy in the treatment of patients with early diabetic retinopathy. Therefore, injury of RPE is the basic condition, not only of the progress of neovascularization, but initiation of early diabetic microangiopathy and macular edema as well. Recently new intravitreal drugs being used in the treatment of eye diseases with increased level of VEGE. Intravitreally administered a human, monoclonal anti-VEGF agent acts only as symptomatic treatment. It does not eliminate hypoxia and requires repeated administration. It is worth emphasizing, that VEGF functions are not limited to active angiogenesis, but also seems to require the maintenance and differentiation of mature blood vessels, such as the choriocapillaris. Therefore, delivery of these anti-VEGF treatments needs to be specific to sites of neovascularization or limited to a short duration, to prevent disruption of the normal vasculature. The effective method, which preserves RPE, improves oxygenation and release traction on the macula, leading to decreased permeability with subsequent resolution in DME, is pars plana vitrectomy with ILM peeling. There are several investigations that support the theoretical value of vitrectomy for the treatment of DME. Intraoperative administration of anti-VEGF agent and corticosteroids may additionally improve results of operative treatment. PMID:19112870
Chmielewska, Katarzyna; Robaszkiewicz, Jacek; Kosatka, Mariusz
Lutein and zeaxanthin, two oxygenated carotenoids, exclusively accumulate in the macula, protecting the underlying photoreceptors and retinal pigment epithelial cells from damaging blue radiation of sunlight. As macular pigment, lutein and zeaxanthin are also potent antioxidants protecting the vulnerable regions of retina from free radical injury. Oxidative stress and cumulative light damage play an important role in pathogenesis of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly population. Antioxidant and lutein supplementation has been shown to decrease the risk and prevent the progression of AMD. The egg yolk is a highly bioavailable source of lutein and zeaxanthin and thus a possible contender for AMD prevention and treatment. Consumption of 2 egg yolks/d for 5 weeks was shown herein to significantly increase serum lutein and zeaxanthin concentration and clinically improve macular pigment concentrations at 0.5° retinal eccentricity in an older adult population taking cholesterol-lowering statins. Four egg yolks/d not only raised serum lutein and zeaxanthin significantly but also macular pigment densities at 0.25°, 0.5° and 1° retinal eccentricity. A positive outcome of the 2 egg yolk consumption was the significant increase in serum HDL-C with a tendency of serum LDL-C to decrease, although not significantly. Four egg yolks/d seemed to cross the threshold for dietary cholesterol tolerance as serum LDL-C tended to increase, although not significantly, despite the significant increase in serum HDL-C. There is a strong possibility that greater build up of lutein and zeaxanthin in the macula may have been observed with 2 egg yolks/d if the intervention period was longer than 5 weeks. Addition of up to 2 eggs a day to the diet is suggested to benefit an older adult population, especially those who are already taking cholesterol-lowering statins by (a) building their macular pigment and possibly protect against AMD and (b) raising serum HDL-C without an adverse affect on serum LDL-C and TC:HDL-C ratio. Increased cholesterol, lutein and zeaxanthin intake from the 2 and 4 egg yolk interventions did not decrease the absorption of other carotenoids, such as alpha-cryptoxanthin, beta-cryptoxanthin, lycopene, alpha-carotene and beta-carotene, tocopherols and retinol from the diet. An unexpected increase was observed in serum alpha-cryptoxanthin and gamma-tocopherol concentrations during the 4 egg yolk phase, these carotenoids are normally present in low concentrations in serum. Lipoprotein distribution of carotenoids and tocopherols was also not affected by the increased egg consumption. In the pursuit of designing a highly bioavailable matrix for lutein/zeaxanthin, similar to the egg yolk micellar matrix, nanoemulsion formulations of lutein were developed using the MicrofluidizerRTM Processor technology. Lutein nanoemulsions are O/W emulsions of lutein which have particle sizes in the nanometer range (? 200 nm). Lutein consumed orally as a nanoemulsion was shown to have significantly greater bioavailability than lutein supplement-pills in pilot-scale clinical studies described here. However, lutein nanoemulsions did not raise plasma lutein concentrations to the same extent as egg yolks in a study performed on BALB/c mice. Formation of mixed micelles in the intestinal lumen during digestion and uptake of these micelles by enterocytes are crucial steps that dictate bioavailability i.e. the proportion of ingested lutein/carotenoid that enters the blood circulation and accumulates in the peripheral tissues such as the macula. In-vitro stomach and intestinal digestion experiments showed lutein nanoemulsions have significantly greater micellarization efficiency compared to egg yolks. Nanoemulsions with a phospholipid (PL) emulsifier containing 80% phosphatidyl choline (PC) or Polysorbate 80 as the emulsifier had better ability to form micelles during the intestinal digestion phase compared to a PL emulsifier with only 45% PC content. The micellar matrix coupled with nanometer sized parti
PURPOSE: To determine the vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor in eyes with rhegmatogenous retinal detachment and proliferative vitreoretinopathy.DESIGN: Prospective, noncomparative case series.METHODS: Pigment epithelium-derived factor and vascular endothelial growth factor concentrations were measured by enzyme-linked immunosorbent assay in 26 eyes with retinal detachment, 6 with proliferative vitreoretinopathy, and 14 with an idiopathic macular hole.RESULTS:
Nahoko Ogata; Maki Nishikawa; Tetsuya Nishimura; Yumiko Mitsuma; Miyo Matsumura
BACKGROUNDIt has been suggested that eating green leafy vegetables, which are rich in lutein and zeaxanthin, may decrease the risk for age related macular degeneration. The goal of this study was to analyse various fruits and vegetables to establish which ones contain lutein and\\/or zeaxanthin and can serve as possible dietary supplements for these carotenoids.METHODSHomogenates of 33 fruits and vegetables,
Olaf Sommerburg; Jan E E Keunen; Alan C Bird; Frederik J G M van Kuijk
We have generated high spatial resolution images showing the distribution of carotenoid macular pigments in the human retina using Raman spectroscopy. A low level of macular pigments is associated with an increased risk of developing age-related macular degeneration, a leading cause of irreversible blindness. Using excised human eyecups and resonant excitation of the pigment molecules with narrow bandwidth blue light from a mercury arc lamp, we record Raman images originating from the carbon-carbon double bond stretch vibrations of lutein and zeaxanthin, the carotenoids comprising human macular pigments. Our Raman images reveal significant differences among subjects, both in regard to absolute levels as well as spatial distribution within the macula. Since the light levels used to obtain these images are well below established safety limits, this technique holds promise for developing a rapid screening diagnostic in large populations at risk for vision loss from age-related macular degeneration.
Gellermann, Werner; Emakov, Igor V.; McClane, Robert W.
Twenty-eight patients with advanced neovascular age-related macular degeneration (AMD) were given a sin- gle intravitreous injection of an E1-, partial E3-, E4-deleted adenoviral vector expressing human pigment ep- ithelium-derived factor (AdPEDF.11). Doses ranging from 106 to 109.5 particle units (PU) were investigated. There were no serious adverse events related to AdPEDF.11 and no dose-limiting toxicities. Signs of mild, transient intraocular
Peter A. Campochiaro; Quan Dong Nguyen; Syed Mahmood Shah; Michael L. Klein; Eric Holz; Robert N. Frank; David A. Saperstein; Anurag Gupta; J. Timothy Stout; Jennifer Macko; Robert DiBartolomeo; Lisa L. Wei
A comparison of macular pigment optical density (MPOD) spatial profiles determined by an optical and a psychophysical technique is presented. We measured the right eyes of 19 healthy individuals, using fundus reflectometry at 0, 1, 2, 4, 6, and 8 deg eccentricity; and heterochromatic flicker photometry (HFP) at 0, 0.5, 1, 2, 3, 4, 5, 6, and 7 deg, and a reference point at 8 deg eccentricity. We found a strong correlation between the two techniques. However, the absolute estimates obtained by fundus reflectometry data were higher than by HFP. These differences could partly be explained by the fact that at 8 deg eccentricity the MPOD is not zero, as assumed in HFP. Furthermore, when performing HFP for eccentricities of <1 deg, we had to assume that subjects set flicker thresholds at 0.4 deg horizontal translation when using a 1-deg stimulus. MPOD profiles are very similar for both techniques if, on average, 0.05 DU is added to the HFP data at all eccentricities. An additional correction factor, dependent on the steepness of the MPOD spatial distribution, is required for 0 deg. PMID:20059284
van der Veen, Rob L P; Berendschot, Tos T J M; Makridaki, Maria; Hendrikse, Fred; Carden, David; Murray, Ian J
A comparison of macular pigment optical density (MPOD) spatial profiles determined by an optical and a psychophysical technique is presented. We measured the right eyes of 19 healthy individuals, using fundus reflectometry at 0, 1, 2, 4, 6, and 8 deg eccentricity; and heterochromatic flicker photometry (HFP) at 0, 0.5, 1, 2, 3, 4, 5, 6, and 7 deg, and a reference point at 8 deg eccentricity. We found a strong correlation between the two techniques. However, the absolute estimates obtained by fundus reflectometry data were higher than by HFP. These differences could partly be explained by the fact that at 8 deg eccentricity the MPOD is not zero, as assumed in HFP. Furthermore, when performing HFP for eccentricities of <1 deg, we had to assume that subjects set flicker thresholds at 0.4 deg horizontal translation when using a 1-deg stimulus. MPOD profiles are very similar for both techniques if, on average, 0.05 DU is added to the HFP data at all eccentricities. An additional correction factor, dependent on the steepness of the MPOD spatial distribution, is required for 0 deg.
van der Veen, Rob L. P.; Berendschot, Tos T. J. M.; Makridaki, Maria; Hendrikse, Fred; Carden, David; Murray, Ian J.
Purpose To report the effect of intravitreal ranibizumab therapy for serous and vascular pigment epithelial detachments (PED) associated with choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD). Methods In a prospective study, best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) data were collected for 62 eyes of 62 patients, with serous or vascular PED associated with CNV secondary to AMD. Intravitreal ranibizumab 0.5 mg was administered with a loading phase of three consecutive monthly injections, followed by monthly review with further treatment, as indicated according to the retreatment criteria of the PrONTO study. The change in visual acuity and PED height from baseline to month 12 after the first injection was determined. Results Sixty-one eyes of 61 patients (one of the patients developed retinal pigment epithelial tear and was excluded from the study) were assessed at the 12-month follow-up examination. There were two types of PED, including vascular PED in 32 patients (Group A) and serous PED (Group B) in 29 patients. The mean improvement of mean BCVA from baseline to 12 months was 0.09 logMAR (Logarithm of the Minimum Angle of Resolution) in Group A and 0.13 logMAR in Group B. Both groups showed significant improvement of the mean BCVA 12 months after the first injection compared with the baseline value (P < 0.05). In relation to the PED height, the mean decrease of mean PED height from baseline to 12 months was 135 ?m in Group A and 180 ?m in Group B. Both groups showed significant reduction of the PED height during the follow-up period (P < 0.01). The PED anatomical response to ranibizumab was not correlated with the BCVA improvement in any of the groups. Apart from one patient who developed pigment epithelial tear no other complications were documented. Conclusion Ranibizumab is an effective and safe treatment for improving vision in patients with serous and vascular PED, although the anatomical response of the PED to ranibizumab may not correlate directly with the visual outcome.
Panos, Georgios D; Gatzioufas, Zisis; Petropoulos, Ioannis K; Dardabounis, Doukas; Thumann, Gabriele; Hafezi, Farhad
Background To evaluate the efficacy of combined photodynamic therapy (PDT) and intravitreal bevacizumab injection in eyes with a serous\\u000a pigment epithelial detachment (PED) associated with age-related macular degeneration (AMD).\\u000a \\u000a \\u000a \\u000a Methods Twenty-two eyes with a serous PED exceeding two disc areas associated with AMD with choroidal vascular abnormalities [choroidal\\u000a neovascularization (n?=?10), polypoidal choroidal vasculopathy (n?=?9), and retinal angiomatous proliferation (n?=?3)] received combined PDT
Chiharu Shima; Fumi Gomi; Miki Sawa; Hirokazu Sakaguchi; Motokazu Tsujikawa; Yasuo Tano
BACKGROUND: The primary objective of LUTEGA is to determine the long-term effect of a supplementation with fixed combination of lutein, zeaxanthin, omega-3-longchain-polyunsaturated-fatty-acids (O-3-LCPUFAs) and antioxidants on macular pigment optical density (MPOD) in patients with non-exudative age-related macular degeneration (AMD). METHODS: The LUTEGA study is a double-blind, placebo-controlled clinical trial. 172 patients with non-exudative AMD were enrolled and randomized to three treatment arms. Supplementation included either once (dosage D1) or twice daily (dosage D2) of 10 mg L / 1 mg Z/ O-3-LCPUFAs (thereof 100 mg DHA, 30 mg EPA)/ antioxidants, or placebo (P). After best-corrected visual acuity (BCVA) test, blood sample was collected and MPOD was measured using the 1-wavelength-reflection method and recording reflection images at 480 nm (modified Visucam(NM/FA), Carl Zeiss Meditec, Germany). During 1 year of intervention, AMD patients were followed up after 1, 3, 6 and 12 months. 145 AMD patients (D1?=?50, D2?=?55, P?=?40) completed the study. RESULTS: After 12 months of intervention, the MPOD parameters (volume, area, maxOD, meanOD) increased significantly in treatment arms D1 and D2 (p?0.001). Volume of MPOD showed the highest within-group difference and increased significantly in D1 and D2, and decreased significantly in P (p?=?0.041). Between-group comparison of absolute changes of all MPOD parameters were significantly different between D1 and P as well as D2 and P with p?0.001 at end point (t?=?12). BCVA, measured in log MAR, improved in D1 and in D2 (p?0.001). After 12 months of intervention, the mean improvement in BCVA was significant in D2 (p?=?0.006) and D1 (p?=?0.038) compared to P. CONCLUSIONS: The supplementation of L, Z, O-3-LCPUFAs and antioxidants resulted in considerable increase in MPOD. There was no difference in accumulation of MPOD between both dosages. Thus, we believe that the used supplementation with L and Z seems to reach a saturation level in retinal cell structure. Additionally, the constant supplementation of L, Z, O-3-LCPUFAs and antioxidants in AMD patients seems to be useful, because MPOD reduces without supplementation. We conclude that the supplementation caused an increase of MPOD, which results in an improvement and stabilization in BCVA in AMD patients. Thus, a protective effect on the macula in AMD patients is assumed. PMID:23695657
Dawczynski, Jens; Jentsch, Susanne; Schweitzer, Dietrich; Hammer, Martin; Lang, Gabriele E; Strobel, Jürgen
Summary. Staphylococcus aureus mutants lacking pigment, or expressing only low levels of pigment, were more sensitive to oleic acid than were the parent strain and mutants making more pigment than the parent. One class of mutants (colour index 5), although possessing significant levels of pigment, were nevertheless quite sensitive to oleic acid. This suggested that only certain carotenoids in the
Z. Xiong; F. A. Kapral
Age-related macular degeneration (ARMD) is the leading cause for visual impairment and blindness in the elder population. Laser photocoagulation, photodynamic therapy and excision of neovascular membranes have met with limited success. Submacular transplantation of autologous iris pigment epithelial (IPE) cells has been proposed to replace the damaged retinal pigment epithelium following surgical removal of the membranes. We tested our hypothesis that the subretinal transplantation of genetically modified autologous IPE cells expressing biological therapeutics might be a promising strategy for the treatment of ARMD and other retinal disorders. Pigment epithelium-derived factor (PEDF) has strong antiangiogenic and neuroprotective activities in the eye. Subretinal transplantation of PEDF expressing IPE cells inhibited pathological choroidal neovascularization in rat models of laser-induced rupture of Bruch's membrane and of oxygen induced ischemic retinopathy. PEDF expressing IPE transplants also increased the survival and preserved rhodopsin expression of photoreceptor cells in the RCS rat, a model of retinal degeneration. These findings suggest a promising concept for the treatment of ARMD and other retinal disorders.
Semkova, Irina; Kreppel, Florian; Welsandt, Gerhard; Luther, Thomas; Kozlowski, Jolanta; Janicki, Hanna; Kochanek, Stefan; Schraermeyer, Ulrich
Concentrations of inflammatory factors were measured in 40 patients with macular edema due to major branch retinal vein occlusion (BRVO) or macular BRVO who were treated by pars plana vitrectomy. Vitreous fluid levels of vascular endothelial growth factor (VEGF), soluble intercellular adhesion molecule-1 (sICAM-1), and pigment epithelium-derived factor (PEDF) were determined. Visual acuity and central macular thickness were significantly improved at 6 months in both groups. Vitreous fluid levels of VEGF and sICAM-1 were higher in the major BRVO group than the macular BRVO group, while the PEDF level was lower in the major group than the macular group. The mean visual acuity and central macular thickness at 6 months were not significantly different between the macular and major groups. In conclusion, patients with major BRVO had higher vitreous levels of inflammatory factors and lower vitreous levels of anti-inflammatory PEDF. Accordingly, regulating inflammatory factors might be more important in major BRVO than macular BRVO. PMID:22269605
Noma, Hidetaka; Funatsu, Hideharu; Mimura, Tatsuya; Eguchi, Shuichiro; Shimada, Katsunori
Purpose Intravitreal somatostatin (SST) levels are decreased in patients with diabetic macular oedema. This deficit may be involved in the pathogenesis of this condition. The aim of the present study was to determine SST concentration in the vitreous fluid of patients with chronic uveitic macular oedema (CUMO) and quiescent intraocular inflammation. Methods Plasma and vitreous fluid samples were obtained during vitrectomy from 11 eyes of patients with CUMO and from 42 eyes of control subjects (idiopathic epiretinal membrane, macular hole). SST concentration was measured by radioimmunoassay. Statistics: ?2-square test, Mann–Whitney U-test, Wilcoxon test, Spearman's rank correlation coefficient, and multivariant linear regression models. Results Plasma SST concentrations were similar in uveitic patients and controls (28.25?pg/ml (21.3–31) vs 28.7?pg/ml (22–29.5); P=0.869). A higher vitreous concentration of proteins was found in uveitic patients (1.59±0.38?mg/ml vs 0.73±0.32?mg/ml, P<0.0001). Vitreous SST was markedly lower in uveitic patients, both in absolute terms and after adjusting for total intravitreous protein concentration (39.37?pg/ml (6.16–172) vs 486.73?pg/ml (4.7–1833), P<0.0001; 33.1?pg/mg (3.9–215.74) vs 629.75?pg/mg (6.91–2024), P<0.0001). No correlations were found between plasma and vitreous concentration of SST in either group (?=0.191, P=0.57 and ?=0.49, P=0.66). There were no correlations between vitreous SST concentration and visual acuity or macular thickness in uveitic patients (?=0.302, P=0.31 and ?=0.45, P=0.13). Conclusions Intravitreous SST is decreased in patients with CUMO and quiescent intraocular inflammation. The deficit of SST may have a role in the pathogenesis of this condition.
Fonollosa, A; Coronado, E; Catalan, R; Gutierrez, M; Macia, C; Zapata, M A; Martinez-Alday, N; Simo, R; Garcia-Arumi, J
Deimination is a form of protein posttranslational modification carried out by the peptidyl arginine deiminases (PADs) enzymes. PAD2 is the principal deiminase expressed in the retina. Elevated levels of PAD2 and protein deimination are present in a number of human neurological diseases, with or without ocular manifestation. To define the association of deimination with the pathogenesis of age-related macular degeneration (AMD), we studied protein deimination and PAD2 levels in retinas of AMD donor eyes compared to age-matched non-AMD retinas. Eyes from non-AMD and AMD donors were fixed in 4% paraformaldehyde and 0.5% glutaraldehyde in phosphate buffer. Retina and retinal pigment epithelium (RPE) from donor eyes were processed for immunohistochemical detection and western blotting using antibodies to PAD2 and citrulline residues. The ganglion cell, inner plexiform, inner nuclear and outer nuclear layers were labeled by both PAD2 and citrulline antibodies. Changes in the localization of deiminated residues and PAD2 were evident as the retinal layers were remodeled coincident with photoreceptor degeneration in AMD retinas. Immunodetection of either PAD2 or citrulline residues could not be evaluated in the RPE layer due to the high autofluorescence levels in this layer. Interestingly, higher deimination immunoreactivity was detected in AMD retinal lysates. However, no significant changes in PAD2 were detected in the AMD and non-AMD retinas and RPE lysates. Our observations show increased levels of protein deimination but not PAD2 in AMD retinas and RPE, suggesting a reduced rate of turnover of deiminated proteins in these AMD retinas. PMID:23562679
Bonilha, Vera L; Shadrach, Karen G; Rayborn, Mary E; Li, Yong; Pauer, Gayle J T; Hagstrom, Stephanie A; Bhattacharya, Sanjoy K; Hollyfield, Joe G
Background Age-related macular degeneration (AMD) is a leading cause of blindness that affects the central region of the retinal pigmented epithelium (RPE), choroid, and neural retina. Initially characterized by an accumulation of sub-RPE deposits, AMD leads to progressive retinal degeneration, and in advanced cases, irreversible vision loss. Although genetic analysis, animal models, and cell culture systems have yielded important insights into AMD, the molecular pathways underlying AMD's onset and progression remain poorly delineated. We sought to better understand the molecular underpinnings of this devastating disease by performing the first comparative transcriptome analysis of AMD and normal human donor eyes. Methods RPE-choroid and retina tissue samples were obtained from a common cohort of 31 normal, 26 AMD, and 11 potential pre-AMD human donor eyes. Transcriptome profiles were generated for macular and extramacular regions, and statistical and bioinformatic methods were employed to identify disease-associated gene signatures and functionally enriched protein association networks. Selected genes of high significance were validated using an independent donor cohort. Results We identified over 50 annotated genes enriched in cell-mediated immune responses that are globally over-expressed in RPE-choroid AMD phenotypes. Using a machine learning model and a second donor cohort, we show that the top 20 global genes are predictive of AMD clinical diagnosis. We also discovered functionally enriched gene sets in the RPE-choroid that delineate the advanced AMD phenotypes, neovascular AMD and geographic atrophy. Moreover, we identified a graded increase of transcript levels in the retina related to wound response, complement cascade, and neurogenesis that strongly correlates with decreased levels of phototransduction transcripts and increased AMD severity. Based on our findings, we assembled protein-protein interactomes that highlight functional networks likely to be involved in AMD pathogenesis. Conclusions We discovered new global biomarkers and gene expression signatures of AMD. These results are consistent with a model whereby cell-based inflammatory responses represent a central feature of AMD etiology, and depending on genetics, environment, or stochastic factors, may give rise to the advanced AMD phenotypes characterized by angiogenesis and/or cell death. Genes regulating these immunological activities, along with numerous other genes identified here, represent promising new targets for AMD-directed therapeutics and diagnostics. Please see related commentary: http://www.biomedcentral.com/1741-7015/10/21/abstract
Purpose. To complete identification of the major components of the human macular pigment. Methods. Chemical ionization mass spectra of the macular pigment components were obtained and compared with those of zeaxanthin and lutein standards. A comparison was also made using chiral column high-performance liquid chroinatography, which is capable of resolving individual stereoisomers of these carotenoids. Zeaxanthin and lutein from human
Richard A. Bone; John T. Landrum; George W. Hime; Araceli Cains
Drusen are subretinal pigment epithelial deposits that are characteristic of but not uniquely associated with age-related macular degeneration (AMD). Age-related macular degeneration is associated with two types of drusen that have different clinical appearances and different prognoses. Hard drusen appear as small, punctate, yellow nodules and can precede the development of atrophic AMD. Areolar atrophy of the retinal pigment epithelium
Ahmed Abdelsalam; Lucian Del Priore; Marco A Zarbin
Purpose: My aim was to evaluate the effect of intravitreal bevacizumab and to determine the concentrations of inflammatory cytokines in patients with macular edema due to branch retinal vein occlusion (BRVO), according to the site of the occlusion. Methods: In a prospective interventional case series, 46 eyes of patients with macular edema due to major (n = 30) or macular
Ji Won Lim
AIMS—To evaluate alteration of plasma malondialdehyde (MDA) and nitric oxide (NO) levels in patients with exudative age related macular degeneration (ARMD).?METHODS—Plasma nitrite plus nitrate concentrations as an index of plasma NO levels and plasma MDA level as a marker of lipid peroxidation were measured in patients with exudative ARMD and age and sex matched healthy subjects.?RESULTS—Significantly higher MDA and lower NO levels were detected in plasma of patients with ARMD compared with their controls (p=0.01, p=0.001, respectively).?CONCLUSION—The results may support involvement of oxidative damage and vascular theory in the pathogenesis of ARMD as part of the ageing process.??
Totan, Y.; Cekic, O.; Borazan, M.; Uz, E.; Sogut, S.; Akyol, O.
Macular amyloidosis is a major cause of skin pigmentation and a rare form of localized primary cutaneous amyloidosis in western countries, with a higher prevalence in Asia and South America. The etiopathogenesis of macular amyloidosis has not yet been fully clarified; a number of risk factors are involved, among them chronic friction in particular. A 54-year-old patient with macular amyloidosis is presented. The diagnosis of macular amyloidosis was based on history data on long-term persistence of the disorder, localized pruritus and constant scratching urge, grayish-brown pigmentation over the scapula, and detection of amyloid in histologic slides. Three-month tretinoin therapy resulted in pruritus alleviation, with no change in the appearance of hyperpigmentation. The exact incidence of macular amyloidosis in Croatia is not known, however, the issue appears to be underestimated or neglected in dermatology routine. PMID:18812063
Rados, Jaka; Marinovi? Kulisi?, Sandra; Lipozenci?, Jasna; Budimci?, Dragomir; Loncari?, Davorin
Age-related macular degeneration (AMD) is a major cause of loss of central vision in the elderly. The formation of drusen, an extracellular, amorphous deposit of material on Bruch's membrane in the macula of the retina, occurs early in the course of the disease. Although some of the molecular components of drusen are known, there is no understanding of the cell biology that leads to the formation of drusen. We have previously demonstrated increased mitochondrial DNA (mtDNA) damage and decreased DNA repair enzyme capabilities in the rodent RPE/choroid with age. In this study, we found that drusen in AMD donor eyes contain markers for autophagy and exosomes. Furthermore, these markers are also found in the region of Bruch's membrane in old mice. By in vitro modeling increased mtDNA damage induced by rotenone, an inhibitor of mitochondrial complex I, in the RPE, we found that the phagocytic activity was not altered but that there were: 1) increased autophagic markers, 2) decreased lysosomal activity, 3) increased exocytotic activity and 4) release of chemoattractants. Exosomes released by the stressed RPE are coated with complement and can bind complement factor H, mutations of which are associated with AMD. We speculate that increased autophagy and the release of intracellular proteins via exosomes by the aged RPE may contribute to the formation of drusen. Molecular and cellular changes in the old RPE may underlie susceptibility to genetic mutations that are found in AMD patients and may be associated with the pathogenesis of AMD in the elderly.
Wang, Ai Ling; Lukas, Thomas J.; Yuan, Ming; Du, Nga; Tso, Mark O.; Neufeld, Arthur H.
Purpose. To evaluate the effect of lysosomal destabilization on NLRP3 inflammasome activation in RPE cells and to investigate the mechanisms by which inflammasome activation may contribute to the pathogenesis of age-related macular degeneration (AMD). Methods. Human ocular tissue sections from patients with geographic atrophy or neovascular AMD were stained for NLRP3 and compared to tissues from age-matched controls. Expression of the IL-1? precursor, pro-IL-1?, was induced in ARPE-19 cells by IL-1? treatment. Immunoblotting was performed to assess expression of NLRP3 inflammasome components (NLRP3, ASC, and procaspase-1) and pro-IL-1? in ARPE-19 cells. Lysosomes were destabilized using the lysosomotropic agent L-leucyl-L-leucine methyl ester (Leu-Leu-OMe). Active caspase-1 was detected using FAM-YVAD-FMK, a fluorescent-labeled inhibitor of caspases (FLICA) specific for caspase-1. IL-1? was detected by immunoblotting and ELISA, and cytotoxicity was evaluated by LDH quantification. Results. RPE of eyes affected by geographic atrophy or neovascular AMD exhibited NLRP3 staining at lesion sites. ARPE-19 cells were found to express NLRP3, ASC, and procaspase-1. IL-1? dose-dependently induced pro-IL-1? expression in ARPE-19 cells. Lysosomal destabilization induced by Leu-Leu-OMe triggered caspase-1 activation, IL-1? secretion, and ARPE-19 cell death. Blocking Leu-Leu-OMe–induced lysosomal disruption with the compound Gly-Phe-CHN2 or inhibiting caspase-1 with Z-YVAD-FMK abrogated IL-1? release and ARPE-19 cytotoxicity. Conclusions. NLRP3 upregulation occurs in the RPE during the pathogenesis of advanced AMD, in both geographic atrophy and neovascular AMD. Destabilization of RPE lysosomes induces NLRP3 inflammasome activation, which may contribute to AMD pathology through the release of the proinflammatory cytokine IL-1? and through caspase-1-mediated cell death, known as “pyroptosis.”
Tseng, Wen Allen; Thein, Thuzar; Kinnunen, Kati; Lashkari, Kameran; Gregory, Meredith S.; D'Amore, Patricia A.; Ksander, Bruce R.
Cigarette smoke is the most important environmental risk factor for developing age-related macular degeneration (AMD). Damage to the retinal pigment epithelium (RPE) caused by cigarette smoke may underlie the etiology of AMD. This study investigated the molecular and cellular effects of cigarette smoke exposure on human RPE cells. ARPE-19 or primary human RPE cells were exposed to cigarette smoke extract (CSE) or hydroquinone (HQ), a component of cigarette smoke. The effect of this exposure on key aspects of RPE vitality including viability, cell size, mitochondrial membrane potential (DeltaPsi(m)), superoxide production, 4-hydroxy-2-nonenal (4-HNE), vascular endothelial growth factor (VEGF), and heme oxygenase-1 (HO-1) expression was determined. Exposure of RPE cells to CSE or HQ caused oxidative damage and apoptosis, characterized by a reduction in cell size and nuclear condensation. Evidence of oxidative damage also included increased lipid peroxidation (4-HNE) and mitochondrial superoxide production, as well as a decrease in intracellular glutathione (GSH). Exogenous administration of antioxidants (GSH and N-acetyl-cysteine) prevented oxidative damage to the RPE cells caused by CSE. Cigarette smoke also induced expression of VEGF, HO-1, and the transcription factor nuclear factor erythroid-derived 2, like 2 (NRF2). However, NRF2 was only modestly involved in CSE-induced HO-1 expression, as shown by the NRF2 small interfering RNA studies. These new findings demonstrate that cigarette smoke is a potent inducer of oxidative damage and cell death in human RPE cells. These data support the hypothesis that cigarette smoke contributes to AMD pathogenesis by causing oxidative damage and cell death to RPE cells. PMID:19759330
Bertram, Kurt M; Baglole, Carolyn J; Phipps, Richard P; Libby, Richard T
Purpose To study the effect of subtoxic levels of hydrogen peroxide (H2O2) on the expression and release of interleukin-6 (IL-6) by cultured retinal pigment epithelial (RPE) cells and to explore the relevant signal pathways. Methods Cultured human RPE cells were stimulated with various subtoxic concentrations of H2O2 for different periods. Conditioned medium and cells were collected. IL-6 in the medium and IL-6 mRNA in the collected cells were measured using an IL-6 enzyme-linked immunosorbent assay kit and reverse transcriptase polymerase chain reaction, respectively. Nuclear factor-kappaB (NF-?B) in nuclear extracts and phosphorylated p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinases (JNK) in cells cultured with and without H2O2 were measured by NF-?B and MAPK enzyme-linked immunosorbent assay kits. Inhibitors of p38 (SB203580), ERK (UO1026), JNK (SP600125), and NF-?B (BAY11–7082) were added to the cultures before the addition of H2O2 to test their effects. Results Subtoxic levels of H2O2 (100 µM and less) increased the IL-6 mRNA level and the release of IL-6 protein by the cultured human RPE cells in a dose- and time-dependent manner. This was accompanied by an increase of NF-?B in nuclear extracts and phosphorylated p38 MAPK, ERK, and JNK in cell lysates, particularly in the p38 and NF-?B. The NF-?B inhibitor decreased the H2O2-induced expression of IL-6. The p38 inhibitor, but not the ERK or JNK inhibitor, completely abolished H2O2-induced expression of IL-6 by RPE cells. The p38 inhibitor also abolished the increase of NF-?B in nuclear extracts in cells treated with H2O2. Conclusions H2O2 stimulated the production of IL-6, a key factor in the modulation of immune responses, inflammatory processes, and the occurrence of autoimmune diseases, which recently has been documented to be increased in age-related macular degeneration (AMD). This may be a molecular linkage for the oxidative stress and inflammatory/autoimmune reactions in AMD and may provide a novel target for the treatment of AMD.
Wu, Wen-Chuan; Gao, Hua-Xin; Chen, Min; Wang, Dawei; Rosen, Richard; McCormick, Steven A.
Age-related macular degeneration (AMD) is a leading cause of blindness and is the third leading cause of blindness. Genetic factors are known to influence an individual's risk for developing AMD. Linkage has earlier been shown to the vascular endothelial growth factor 2 (VEGF2) gene and AMD. To examine the role of VEGFR2 in north Indian population, we conducted a case control study. Total 176 subjects were enrolled in a case-control genetic study. Real-Time PCR was used to analyze the SNPs (rs1531289 and rs2305948) of VEGFR-2 gene. ELISA was conducted to determine the levels of VEGFR2. A non-parametric Mann-Whitney-U test was applied for comparison of the ELISA levels and pearson's Chi-square test was applied to study the association of polymorphism between various groups. The single SNP (rs1531289) AG genotype was significantly associated with AMD (OR= 2.13, 95%CI= 1.011-4.489, P=0.047). VEGFR2 levels were found to be increased significantly in AMD patients as compared to normal controls. We also found significant increase in the levels of wet AMD as compared to dry AMD. This study demonstrates higher levels of VEGFR2 and frequency of AG (rs1531289) genotype in AMD patient population, suggesting the role of VEGFR-2 in pathogenesis of AMD. PMID:23030506
Sharma, Neel Kamal; Gupta, Amod; Prabhakar, Sudesh; Singh, Ramandeep; Sharma, Suresh; Anand, Akshay
Cannabinoid receptors and the endocannabinoids (anandamide (N-arachidonoylethanolamine—AEA) and 2-arachidonoylglycerol (2-AG)), as well as the AEA congener, palmitoylethanolamide (PEA), are involved in ocular physiology. We measured endocannabinoid and PEA levels by isotope-dilution liquid chromatography-mass spectrometric analysis in post-mortem eye tissues of patients with diabetic retinopathy (DR) or age-related macular degeneration (AMD). In eyes with DR, significantly enhanced levels of AEA were
I. Matias; J. W. Wang; A. Schiano Moriello; A. Nieves; D. F. Woodward; V. Di Marzo
Purpose Recent evidence has suggested a correlation between reduced vitamin D levels and delayed angiogenesis and reduced inflammatory response, which are known to have a major role in the development and progression of age-related macular degeneration (AMD). Design Cross-sectional study. Participants Members of the Maccabi Healthcare Services (MHS, one of the four largest Israeli Health Maintenance Organization) aged ?60 years, whose vitamin D levels were taken as part of routine examinations between 2000 and 2008. Methods All data for this study were obtained from MHS databases that include medical information on 1.8 million subscribers. Main outcome measures Serum 25-OH vitamin D levels. Results The total study population comprised of 1045 members diagnosed as having AMD, and 8124 as non-AMD, for whom there was information on vitamin D levels. The mean±SD level of 25-OH vitamin D was 24.1±9.41?ng/ml (range 0.8–120) for the AMD patients and 24.13±9.50?ng/ml (range 0.0–120) for the controls (P=ns). One-third (33.6%) of the AMD patients and 32.86% of the controls had a 25-OH vitamin D level <16?ng/ml, and the proportions of tests in which the 25-OH vitamin D level was >74?ng/ml were 0.19 and 0.14%, respectively (P=ns) Conclusions No association was detected between vitamin D levels and the presence of AMD in this cross-sectional study. These results raise some doubt about an association between reduced vitamin D levels and the prevalence of AMD.
Golan, S; Shalev, V; Treister, G; Chodick, G; Loewenstein, A
We investigated an individual macular corneal dystrophy (MCD) type II cornea from a 42-year-old woman with markedly reduced antigenic keratan sulphate levels. A characteristic 4.6 Ĺ X-ray reflection was evident, and the mid-stroma contained 30% less sulphur than normal. Close packing of collagen was restricted to the superficial stroma. Abnormally large proteoglycan filaments were noted throughout the extracellular matrix and
Andrew J Quantock; Nigel J Fullwood; Eugene J-M A Thonar; Stephen R Waltman; Malcolm S Capel; Mitsutoshi Ito; Steven M Verity; David J Schanzlin
Three cases of retinal phototoxicity were caused by light from the endoilluminator used in vitrectomy. Preoperative clinical examination, color photography, and fluorescein angiography in all three cases failed to disclose retinal pigment epithelial changes. Postoperative clinical findings, photographs, and fluorescein angiograms are highly suggestive of the presence of retinal phototoxicity. The characteristics of these lesions and surgical conditions implicate the endoilluminator as the source of photic injury. The macular lesions were noted within one week of the surgical procedure, measured between 2 and 5 disk diameters in size, involved the fovea in two eyes, and resulted in marked decrease in visual acuity in two of three eyes, with persistence in one eye. Initially, whitening of the outer retina was present, but was replaced by pigmentary mottling at the level of the retinal pigment epithelium within a few weeks. Preventive measures to avoid macular phototoxicity associated with vitrectomy are discussed. PMID:1524116
Michels, M; Lewis, H; Abrams, G W; Han, D P; Mieler, W F; Neitz, J
Efficacy of Ethanol Extract of Fructus lycii and Its Constituents Lutein/Zeaxanthin in Protecting Retinal Pigment Epithelium Cells against Oxidative Stress: In Vivo and In Vitro Models of Age-Related Macular Degeneration
Age-related macular degeneration (AMD) is a major cause of blindness worldwide. Oxidative stress plays a large role in the pathogenesis of AMD. The present study was to evaluate the effects of Fructus lycii ethanol extract on AMD in mice and to investigate whether combination of lutein and zeaxanthin, two carotenoid pigments in Fructus lycii, could protect human retinal pigment epithelial ARPE-19 cells treated with hydrogen peroxide (H2O2) in vitro. We found that severe sediment beneath retinal pigment epithelium and thickened Bruch membrane occurred in AMD mice. However, Fructus lycii ethanol extract improved the histopathologic changes and decreased the thickness of Bruch membrane. Furthermore, the gene and protein expression of cathepsin B and cystatin C was upregulated in AMD mice but was eliminated by Fructus lycii ethanol extract. Investigations in vitro showed that ARPE-19 cell proliferation was suppressed by H2O2. However, lutein/zeaxanthin not only stimulated cell proliferation but also abrogated the enhanced expression of MMP-2 and TIMP-1 in H2O2-treated ARPE-19 cells. These data collectively suggested that Fructus lycii ethanol extract and its active components lutein/zeaxanthin had protective effects on AMD in vivo and in vitro, providing novel insights into the beneficial role of Fructus lycii for AMD therapy.
Xu, Xinrong; Hang, Li; Huang, Binglin; Wei, Yuanhua; Zheng, Shizhong
PURPOSE: To describe the clinical and histopathologic findings in a 72-year-old woman with North Carolina macular dystrophy. METHODS: Clinical examination was performed by slit-lamp biomicroscopy, indirect ophthalmoscopy, color fundus photography, and focal electroretinography. Histopathologic examination of the enucleated left eye consisted of light microscopy. RESULTS: Light microscopy demonstrated a discrete macular lesion characterized by focal absence of photoreceptor cells and retinal pigment epithelium. Bruch's membrane was attenuated in the center of the lesion and associated with marked atrophy of the choriocapillaris. Adjacent to the central lesion, some lipofuscin was identified in the retinal pigment epithelium. CONCLUSIONS: North Carolina macular dystrophy has both clinical and microscopic appearances of a well-demarcated retinal and pigment epithelial lesion confined to the macula. This is consistent with the clinical impression that it is a focal macular dystrophy.
Small, K W; Voo, I; Flannery, J; Udar, N; Glasgow, B J
PURPOSE: To report the levels of pigment epithelium-derived factor in the vitreous of patients with diabetic retinopathy, rhegmatogenous retinal detachment, and idiopathic macular hole.METHODS: Using enzyme-linked immunosorbent assay, we measured the levels of pigment epithelium-derived factor in the vitreous of 34 eyes of 33 patients who underwent vitrectomy for the treatment of diabetic retinopathy (17 eyes of 16 patients), rhegmatogenous
Nahoko Ogata; Joyce Tombran-Tink; Maki Nishikawa; Tetsuya Nishimura; Yumiko Mitsuma; Taiji Sakamoto; Miyo Matsumura
Purpose. Antioxidant supplements may reduce age-related macular degeneration (AMD) progression. The macular carotenoids are of particular interest because of their biochemical, optical, and anatomic properties. This classic twin study was designed to determine the heritability of macular pigment (MP) augmentation in response to supplemental lutein (L) and zeaxanthin (Z). Methods. A total of 322 healthy female twin volunteers, aged 16–50 years (mean 40 ± 8.7) was enrolled in a prospective, nonrandomized supplement study. Macular pigment optical density (MPOD) measurements using two techniques (2-wavelength fundus autofluorescence [AF] and heterochromatic flicker photometry [HFP]), and serum concentrations of L and Z, were recorded at baseline, and at 3 and 6 months following daily supplementation with 18 mg L and 2.4 mg Z for a study period of 6 months. Results. At baseline, mean MPOD was 0.44 density units (SD 0.21, range 0.04–1.25) using HFP, and 0.41 density units (SD 0.15) using AF. Serum L and Z levels were raised significantly from baseline following 3 months' supplementation (mean increase 223% and 633%, respectively, P < 0.0001 for both), with no MPOD increase. After 6 months' supplementation, a small increase in MPOD was seen (mean increase 0.025 ± 0.16, P = 0.02, using HFP). Subdivision of baseline MPOD into quartiles revealed that baseline levels made no difference to the treatment effect. Genetic factors explained 27% (95% confidence interval [CI] 7–45) of the variation in MPOD response. Distribution profiles of macular pigment did not change in response to supplementation. Conclusions. MPOD response to supplemental L and Z for a period of 6 months was small (an increase over baseline of 5.7% and 3.7%, measured using HFP and AF, respectively), and was moderately heritable. Further study is indicated to investigate the functional and clinical impact of supplementation with the macular carotenoids.
Hammond, Christopher J.; Liew, S. H. Melissa; Van Kuijk, Frederik J.; Beatty, Stephen; Nolan, John M.; Spector, Tim D.; Gilbert, Clare E.
Convergence--the independent evolution of the same trait by two or more taxa--has long been of interest to evolutionary biologists, but only recently has the molecular basis of phenotypic convergence been identified. Here, we highlight studies of rapid evolution of cryptic coloration in vertebrates to demonstrate that phenotypic convergence can occur at multiple levels: mutations, genes and gene function. We first show that different genes can be responsible for convergent phenotypes even among closely related populations, for example, in the pale beach mice inhabiting Florida's Gulf and Atlantic coasts. By contrast, the exact same mutation can create similar phenotypes in distantly related species such as mice and mammoths. Next, we show that different mutations in the same gene need not be functionally equivalent to produce similar phenotypes. For example, separate mutations produce divergent protein function but convergent pale coloration in two lizard species. Similarly, mutations that alter the expression of a gene in different ways can, nevertheless, result in similar phenotypes, as demonstrated by sister species of deer mice. Together these studies underscore the importance of identifying not only the genes, but also the precise mutations and their effects on protein function, that contribute to adaptation and highlight how convergence can occur at different genetic levels. PMID:20643733
Manceau, Marie; Domingues, Vera S; Linnen, Catherine R; Rosenblum, Erica Bree; Hoekstra, Hopi E
Convergence—the independent evolution of the same trait by two or more taxa—has long been of interest to evolutionary biologists, but only recently has the molecular basis of phenotypic convergence been identified. Here, we highlight studies of rapid evolution of cryptic coloration in vertebrates to demonstrate that phenotypic convergence can occur at multiple levels: mutations, genes and gene function. We first show that different genes can be responsible for convergent phenotypes even among closely related populations, for example, in the pale beach mice inhabiting Florida's Gulf and Atlantic coasts. By contrast, the exact same mutation can create similar phenotypes in distantly related species such as mice and mammoths. Next, we show that different mutations in the same gene need not be functionally equivalent to produce similar phenotypes. For example, separate mutations produce divergent protein function but convergent pale coloration in two lizard species. Similarly, mutations that alter the expression of a gene in different ways can, nevertheless, result in similar phenotypes, as demonstrated by sister species of deer mice. Together these studies underscore the importance of identifying not only the genes, but also the precise mutations and their effects on protein function, that contribute to adaptation and highlight how convergence can occur at different genetic levels.
Manceau, Marie; Domingues, Vera S.; Linnen, Catherine R.; Rosenblum, Erica Bree; Hoekstra, Hopi E.
High levels of n-3 polyunsaturated fatty acids and a low level of arachidonic acid (ARA, 20:4n-6) in larval diets seem to be necessary for normal pigmentation of Atlantic halibut juveniles, whereas energy status and fatty acid composition seem to modulate eye migration in flatfish in general. However, we do not know the limits or the critical combinations of essential fatty
Kristin Hamre; Torstein Harboe
PurposeTo investigate whether interleukine-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) are related with macular oedema in patients with branch retinal vein occlusions (BRVOs).DesignRetrospective case–control study.ParticipantsNineteen patients who had macular oedema due to BRVO and nine patients with non-ischaemic ocular diseases (control group).MethodsMacular oedema was examined by optical coherence tomography. Both venous blood and vitreous samples were obtained at the time
A Fonollosa; J Garcia-Arumi; E Santos; C Macia; P Fernandez; R M Segura; M A Zapata; R Rodriguez-Infante; A Boixadera; V Martinez-Castillo
Aim To assess the efficacy of pegaptanib as maintenance therapy in neovascular age-related macular degeneration (NV-AMD) patients after induction therapy. Methods A phase IV, prospective, open-label, uncontrolled exploratory study including subjects with subfoveal NV-AMD who had had one to three induction treatments 30–120?days before entry and showed investigator-determined clinical/anatomical NV-AMD improvement. Lesions in the study eye were: any subtype, 12 or fewer disc areas; postinduction centre point thickness (CPT) 275??m or less or thinning of 100??m or more (optical coherence tomography); visual acuity (VA) 20/20–20/400. Intravitreal pegaptanib 0.3?mg was administered as maintenance every 6?weeks for 48?weeks with follow-up to week 54. Booster treatment additional unscheduled treatment for wet age-related macular degeneration, was allowed in the study eye at the investigators' discretion for clinical deterioration. Results Of 568 enrolled subjects, 86% completed 1?year of pegaptanib. Mean VA improvement during induction (49.6 to 65.5 letters) was well preserved (54-week mean 61.8 letters). Mean CPT was relatively stable during maintenance (20??m increase during the study). Fifty per cent did not receive unscheduled booster treatment to week 54; 46% did have one such booster (mean 147?days after maintenance initiation). Conclusions An induction-maintenance strategy, using non-selective then selective vascular endothelial growth factor (VEGF) inhibitors, could be considered for NV-AMD. This approach may have particular relevance for patients with systemic comorbidities who require long-term anti-VEGF therapy for NV-AMD.
Background Age-related macular degeneration (ARMD) is the most prevalent cause of visual loss in patients older than 60 years in the United States. Observation of drusen is the hallmark finding in the clinical evaluation of ARMD. Objectives To segment and quantify drusen found in patients with ARMD using image analysis and to compare the efficacy of image analysis segmentation with that of stereoscopic manual grading of drusen. Design Retrospective study. Setting University referral center. Patients Photographs were randomly selected from an available database of patients with known ARMD in the ongoing Columbia University Macular Genetics Study. All patients were white and older than 60 years. Interventions Twenty images from 17 patients were selected as representative of common manifestations of drusen. Image preprocessing included automated color balancing and, where necessary, manual segmentation of confounding lesions such as geographic atrophy (3 images). The operator then chose among 3 automated processing options suggested by predominant drusen type. Automated processing consisted of elimination of background variability by a mathematical model and subsequent histogram-based threshold selection. A retinal specialist using a graphic tablet while viewing stereo pairs constructed digital drusen drawings for each image. Main Outcome Measures The sensitivity and specificity of drusen segmentation using the automated method with respect to manual stereoscopic drusen drawings were calculated on a rigorous pixel-by-pixel basis. Results The median sensitivity and specificity of automated segmentation were 70% and 81%, respectively. After preprocessing and option choice, reproducibility of automated drusen segmentation was necessarily 100%. Conclusions Automated drusen segmentation can be reliably performed on digital fundus photographs and result in successful quantification of drusen in a more precise manner than is traditionally possible with manual stereoscopic grading of drusen. With only minor preprocessing requirements, this automated detection technique may dramatically improve our ability to monitor drusen in ARMD.
Smith, R. Theodore; Chan, Jackie K.; Nagasaki, Takayuki; Ahmad, Umer F.; Barbazetto, Irene; Sparrow, Janet; Figueroa, Marta; Merriam, Joanna
Stargardt-like macular degeneration (STGD3) is an early onset, autosomal dominant macular degeneration. STGD3 is characterized by a progressive pathology, the loss of central vision, atrophy of the retinal pigment epithelium, and accumulation of lipofuscin, clinical features that are also characteristic of age-related macular degeneration. The onset of clinical symptoms in STGD3, however, is typically observed within the second or third
Vidyullatha Vasireddy; Paul Wong; Radha Ayyagari
We examined the association of nitrate-nitrogen exposure from rural private drinking water and incidence of age-related macular degeneration (AMD). All participants in the Beaver Dam Eye Study (53916 improvement plan code) completed a questionnaire and had an ocular examination including standardized, graded fundus photographs at five examinations. Only information from rural residents in that study are included in this report. Data from an environmental monitoring study with probabilistic-based agro-chemical sampling, including nitrate-nitrogen, of rural private drinking water were available. Incidence of early AMD was associated with elevated nitrate-nitrogen levels in rural private drinking water supply (10.0% for low, 19.2% for medium, and 26.1% for high nitrate-nitrogen level in the right eye). The odds ratios (ORs) were 1.77 (95% confidence interval [CI]: 1.12-2.78) for medium and 2.88 (95% CI: 1.59-5.23) for high nitrate-nitrogen level. Incidence of late AMD was increased for those with medium or high levels of nitrate-nitrogen compared to low levels (2.3% for low and 5.1% for the medium or high nitrate-nitrogen level, for the right eye). The OR for medium or high nitrate-nitrogen groups was 2.80 (95% CI: 1.07-7.31) compared to the low nitrate-nitrogen group. PMID:24007430
Klein, Barbara E K; McElroy, Jane A; Klein, Ronald; Howard, Kerri P; Lee, Kristine E
We studied the effect of macular grid photocoagulation on the retinal vessels, retina, retinal pigment epithelium, and choroid of normal cynomolgus monkeys. Argon blue-green laser photocoagulation, similar to that employed for treating macular edema due to branch retinal vein occlusion, resulted in a decreased retinal capillary area at both one and five months after treatment. The photoreceptors and retinal pigment epithelium between laser lesions were altered at three days after treatment, but their appearance returned to normal by five months. The significance of these findings is discussed with regard to resolution of macular edema and improvement in vision following grid photocoagulation.
Wilson, D.J.; Finkelstein, D.; Quigley, H.A.; Green, W.R.
Patients with vitiligo often have antibodies to pigment cells. To examine whether is relation between the presence of such antibodies and disease activity, sera of 24 patients with vitiligo (10 with active and 14 with inactive disease) and 19 normal individual were tested for antibodies to pigment cell surface antigens using a live cell enzyme-linked immunoabsorbent assay. IgG pigment cell
Ronald Harning; Jian Cui; Jean-Claude Bystryn
The inherited macular dystrophies are characterized by different grade central visual loss and different character macula atrophy, because of retinal pigment epithelium lesion. The cause of photoreceptors degeneration is still not known. In this article, we review subjective and objective ophthalmological examines essential to diagnosis and differential diagnosis of inherited autosomal dominant and autosomal recessive macular dystrophies. It is known seven gene mutations (ABCA4, ELOVL4, PROML1, VMD2, Peripherin/RDS, TIMP3, XLRS), which may cause inherited macular dystrophies development. Inheritance type of inherited macular dystrophies, prevalence, beginning of disease, spread of the disease between female and male, clinic, electroretinography, electrooculography, differential diagnosis, genetic research and prognosis are also reviewed. PMID:23168924
Liutkevi?ien?, Rasa; Lesauskait?, Vaiva; Ašmonien?, Virginija; Gelžinis, Arvydas; Zali?nien?, Dalia; Jašinskas, Vytautas
There is a mutualistic symbiotic relationship between the components of the photoreceptor/retinal pigment epithelium (RPE)/Bruch’s membrane (BrMb)/choriocapillaris (CC) complex that is lost in AMD. Which component in the photoreceptor/RPE/BrMb/CC complex is affected first appears to depend on the type of AMD. In atrophic AMD (~85–90% of cases), it appears that large confluent drusen formation and hyperpigmentation (presumably dysfunction in RPE) are the initial insult and the resorption of these drusen and loss of RPE (hypopigmentation) can be predictive for progression of geographic atrophy (GA). The death and dysfunction of photoreceptors and CC appear to be secondary events to loss in RPE. In neovascular AMD (~10–15% of cases), the loss of choroidal vasculature may be the initial insult to the complex. Loss of CC with an intact RPE monolayer in wet AMD has been observed. This may be due to reduction in blood supply because of large vessel stenosis. Furthermore, the environment of the CC, basement membrane and intercapillary septa, is a proinflammatory milieu with accumulation of complement components as well as proinflammatory molecules like CRP during AMD. In this toxic milieu, CC die or become dysfunction making adjacent RPE hypoxic. These hypoxic cells then produce angiogenic substances like VEGF that stimulate growth of new vessels from CC, resulting in choroidal neovascularization (CNV). The loss of CC might also be a stimulus for drusen formation since the disposal system for retinal debris and exocytosed material from RPE would be limited. Ultimately, the photoreceptors die of lack of nutrients, leakage of serum components from the neovascularization, and scar formation. Therefore, the mutualistic symbiotic relationship within the photoreceptor/RPE/BrMb/CC complex is lost in both forms of AMD. Loss of this functionally integrated relationship results in death and dysfunction of all of the components in the complex.
Bhutto, Imran; Lutty, Gerard
Owing to the lack of an effective prevention and appropriate treatment, age-related macular degeneration (AMD) continues being\\u000a the leading cause of central vision loss in patients older than 65 yr of age in the first world, and the third cause in developing\\u000a countries. Despite a relatively low prevalence of choroideal neovascularization (CNV) in AMD, approximately a quarter of these\\u000a patients
Peter E. Liggett; Alejandro J. Lavaque
Lipofuscin results from digestion of photoreceptor outer segments by the retinal pigment epithelium (RPE) and is the principal compound that causes RPE fluorescence during autofluorescence imaging. Absorption of the 488-nanometer blue light by macular pigments, especially by the carotenoids lutein and zeaxanthin, causes normal macular hypo-autofluorescence. Fundus autofluorescence imaging is being increasingly employed in ophthalmic practice to diagnose and monitor patients with a variety of retinal disorders. In macular edema for example, areas of hyper-autofluorescence are usually present which are postulated to be due to dispersion of macular pigments by pockets of intraretinal fluid. For this reason, the masking effect of macular pigments is reduced and the natural autofluorescence of lipofuscin can be observed without interference. In cystic types of macular edema, e.g. cystoid macular edema due to retinal vein occlusion, diabetic macular edema and post cataract surgery, hyper-autofluorescent regions corresponding to cystic spaces of fluid accumulation can be identified. In addition, the amount of hyper-autofluorescence seems to correspond to the severity of edema. Hence, autofluorescence imaging, as a noninvasive technique, can provide valuable information on cystoid macular edema in terms of diagnosis, follow-up and efficacy of treatment.
Ebrahimiadib, Nazanin; Riazi-Esfahani, Mohammad
The chloroplast ultrastructure of two Chlamydomonas reinhardtii pigment variant mutants, U3N and U3A, is strikingly different from that of the wild type. The mutant chloroplast has greatly lowered levels of chlorophyll a and b, and lacks the usual ordered thylakoid membrane structure. The amount of chloroplast ribosomes is increased, but the pyrenoid and surrounding starch grains appear to be unaltered. Our biochemical analyses have shown that, while the properties of chloroplast DNA, ribosomal RNA, and ribosomes in these mutants appeared to be normal, their relative amounts per cell increased markedly when compared to the wild type. In U3N these increases were approximately 60% for chloroplast DNA and 80% for chloroplast ribosomes. However, the ratio of chloroplast rDNA genes to total chloroplast DNA remained unchanged as shown by DNA-rRNA hybrdization. We propose that (1) The enhanced level of chloroplast ribosomes in these mutants is a direct consequence of the elevated amount of chloroplast DNA. Both of these increases may, in turn, arise from defective mechanism for their control. (2) These mutants grow successfully in the absence of functional photosynthesis, provided an external carbon source is available to them, but functional plastid DNA, ribosomes and protein synthesis may still be a requirement for normal starch metabolism. PMID:6156947
Wilson, R E; Swift, H; Chiang, K S
Effects of gamma rays on the free polyamine (PA) levels were studied in Vigna radiata (L.) Wilczek. Seeds exposed to different doses of gamma rays were checked for damage on phenotype, germination frequency and alteration in photosynthetic pigments. Free polyamine levels were estimated from seeds irradiated in dry and water imbibed conditions. Polyamine levels of seedlings grown from irradiated seeds, and irradiated seedlings from unexposed seeds were also measured. Damage caused by gamma irradiation resulted in decrease in final germination percentage and seedling height. Photosynthetic pigments decreased in a dose dependent manner as marker of stress. Polyamines decreased in irradiated dry seeds and in seedlings grown from irradiated seeds. Radiation stress induced increase in free polyamines was seen in irradiated imbibed seeds and irradiated seedlings. Response of polyamines towards gamma rays is dependent on the stage of the life cycle of the plant. PMID:23454839
Sengupta, Mandar; Chakraborty, Anindita; Raychaudhuri, Sarmistha Sen
Retinal pigment epithelium (RPE) arises from neuroectoderm and plays a key role in support of photoreceptor functions. Several degenerative eye diseases, such as macular degeneration or retinitis pigmentosa, are associated with impaired RPE function that may lead to photoreceptor loss and blindness. RPE derived from human embryonic stem (hES) cells can be an important source of this tissue for transplantation to cure such degenerative diseases. This chapter describes differentiation of hES cells to RPE, its subsequent isolation, maintenance in culture, and characterization. PMID:17141036
Macular edema is defined as an accumulation of fluid in the outer plexiform layer and the inner nuclear layer as well as a swelling of Müller cells of the retina. It consists of a localized expansion of the retinal extracellular space (sometimes associated with the intracellular space) in the macular area. Macular edema is a common cause of a sudden
Stefan Scholl; Janna Kirchhof; Albert J. Augustin
Abstract Purpose: To describe macular slippage toward the optic disc after macular hole surgery with internal limiting membrane (ILM) peeling. Materials and methods: A total of 27 eyes of 27 patients with idiopathic macular hole were included in this retrospective study. The fovea-to-disc distance (FDD) was measured from digital color fundus images before and at least six months after surgery. The position of the fovea was determined as the center of the macular hole before surgery and the center of the macular pigment area after surgery. The thickness of the nasal and temporal macula was measured using spectral-domain optical coherence tomography. The difference in thickness between the nasal and temporal macula was determined as the degree of parafoveal asymmetry (PFA). Results: The postoperative FDD was significantly shorter than the preoperative FDD: 4.00?±?0.33?mm and 3.82?±?0.34?mm, respectively (p?0.0001). The mean decreased ratio of FDD was 4.68% (range, 0.38-9.24%). The appearance of the dissociated optic nerve fiber layer (DONFL) was finally found in 21 eyes (78%). The decreased FDD ratio was significantly larger in eyes with the DONFL appearance than in those without it: 5.61?±?1.74% and 1.44?±?1.12%, respectively (p?0.0001). The decreased ratio of FDD was correlated with the postoperative PFA (r?=?0.63, p?=?0.0004). Conclusion: A macula in which the ILM has peeled off would slip toward the optic disc after macular hole surgery. Macular slippage can be a reasonable cause for the macular alterations such as an appearance of DONFL and changes in asymmetrical parafoveal thickness. PMID:23885921
Nakagomi, Tomomi; Goto, Teruhiko; Tateno, Yasushi; Oshiro, Tomohiro; Iijima, Hiroyuki
This article provides the reader with practical information to be applied to the various remaining causes of macular edema. Some macular edemas linked to ocular diseases like radiotherapy after ocular melanomas remained of poor functional prognosis due to the primary disease. On the contrary, macular edemas occurring after retinal detachment or after some systemic or local treatment use are often temporary. Macular edema associated with epiretinal membranes or vitreomacular traction is the main cause of poor functional recovery. However, the delay to observe a significant improvement of vision after surgery should be long, as usually observed in tractional myopic vitreoschisis. Finally, some circumstances of macular edemas such as hemangiomas or macroaneurysms should be treated, if symptomatic, with the treatments currently used in diabetic macular edema or exudative macular degeneration. PMID:23264332
Creuzot-Garcher, Catherine; Jonas, Jost; Wolf, Sebastian
This study investigated whether vascular endothelial growth factor (VEGF), soluble intercellular adhesion molecule-1 (sICAM-1), and pigment epithelium-derived factor (PEDF) influence the visual prognosis of patients with macular edema and branch retinal vein occlusion (BRVO). In 47 consecutive patients (47 eyes) undergoing vitrectomy, retinal thickness was examined by optical coherence tomography. Best-corrected visual acuity and the vitreous fluid levels of VEGF, sICAM-1, and PEDF were also determined. Patients were followed for at least 6 months after surgery. Vitreous fluid levels of VEGF and sICAM-1 were significantly lower in the patients with more marked improvement of visual acuity after vitrectomy, while PEDF was significantly higher. VEGF and sICAM-1 levels were significantly higher in patients with greater postoperative improvement of macular edema, while PEDF was significantly lower. In BRVO patients, vitreous fluid levels of VEGF, sICAM-1, and PEDF may influence both the response of macular edema to vitrectomy and the visual prognosis.
Noma, Hidetaka; Funatsu, Hideharu; Mimura, Tatsuya; Eguchi, Shuichiro; Shimada, Katsunori
Purpose. To report a case of full-thickness macular hole (FTMH) formation associated with central serous retinopathy (CSC). Method. Case report. Results. A 63-year-old woman with history of CSC diagnosed 8 years ago presented with vision loss. Clinical examination and optical coherence tomography found FTMH. Seven months following successful surgical repair of the macular hole, the patient presented with decreased vision, and was found to have CSC with closed macular hole. Discussion. Based on the hydration theory of macular hole formation, CSC and the associated retinal pigment epithelium and choriocapillaris dysfunctions may promote the progression of FTMH. PMID:22729443
Amde, Wendewessen; Tewari, Asheesh
Retinal pigment epithelium transplantation has been proposed as adjunctive treatment for age-related macular degeneration following surgical excision of choroidal neovascular membranes. The goal of this study was to develop a model to evaluate retinal pigment epithelium transplantation onto human Bruch's membrane in vitro. We investigated the ability of cultured fetal human retinal pigment epithelium to colonize human cadaver Bruch's membrane,
ALESSANDRO A. CASTELLARIN; ILENE K. SUGINO; JOSEPH A. VARGAS; BARBARA PAROLINI; GE MING LUI; MARCO A. ZARBIN
Purpose To review current knowledge of key pathogenetic pathways in age-related macular disease (AMD). Methods Experimental evidence and clinical observations are reviewed. Results A number of common downstream pathophysiologic pathways appear to be relevant in AMD manifestations irrespective of primary heterogeneous etiologies. These include sequelae of oxidative damage, retinal pigment epithelium (RPE) cell dysfunction with accumulation of lipofuscin and impairment
Felix Roth; Almut Bindewald; Frank G. Holz
Purpose To investigate the influence of the Factor H (CFH) Tyr402His polymorphism on the plasma levels of the alternative pathway proteins CFH, C3, Factor B (FB), Factor D (FD), and Factor I (FI) and the inflammatory marker C-reactive protein (CRP) in 119 patients with age-related macular degeneration (AMD) and 152 unrelated control individuals. Methods Patients with AMD and the control group were separated according to CFH polymorphism, age, and gender. Plasma complement proteins and CRP concentrations were determined with enzyme-linked immunosorbent assay, immunodiffusion, or nephelometry. Results Significant differences in the concentrations of FD and FI were observed between the patients with AMD and the control individuals. We observed significantly reduced FD plasma levels in patients with AMD. We also identified a significant decrease in CFH plasma levels in female patients with AMD in relation to female controls. Plasma FI levels were significantly increased in patients with AMD compared to the control group. Regarding gender, a significant increase in FI plasma levels was observed in male patients. Finally, we found no significant correlation between the CFH Tyr402His polymorphism and the CFH, C3, FB, FD, FI, and CRP plasma levels. Conclusions Patients with AMD present altered levels of FD and FI in a manner independent of this CFH polymorphism, and gender apparently contributes to the plasma levels of these two proteins in patients with AMD and control individuals.
Silva, Aldacilene Souza; Teixeira, Anderson Gustavo; Bavia, Lorena; Lin, Fabio; Velletri, Roberta; Belfort, Rubens
Recent imaging studies have suggested that macular pigment is decreased centrally in macular telangiectasia type 2 (MT2).\\u000a The uptake of xanthophyll pigment into the macula is thought to be facilitated by a xanthophyll-binding protein (XBP). The\\u000a Pi isoform of glutathione S-transferase (GSTP1) represents one such XBP with high binding affinity. This case–control study aimed to determine whether\\u000a two common single-nucleotide
Joshua A. Szental; Paul N. Baird; Andrea J. Richardson; F. M. Amirul Islam; Hendrik P. N. Scholl; Peter Charbel Issa; Frank G. Holz; Mark Gillies; Robyn H. Guymer
The pericarp of Capsicum fruit is a rich dietary source of carotenoids. Accumulation of these compounds may be controlled, in part, by gene transcription of biosynthetic enzymes. The carotenoid composition in a number of orange-coloured C. annuum cultivars was determined using HPLC and compared with transcript abundances for four carotenogenic enzymes, Psy, LcyB, CrtZ-2, and Ccs determined by qRT-PCR. There were unique carotenoid profiles as well as distinct patterns of transcription of carotenogenic enzymes within the seven orange-coloured cultivars. In one cultivar, ‘Fogo’, carrying the mutant ccs-3 allele, transcripts were detected for this gene, but no CCS protein accumulated. The premature stop termination in ccs-3 prevented expression of the biosynthetic activity to synthesize the capsanthin and capsorubin forms of carotenoids. In two other orange-coloured cultivars, ‘Orange Grande’ and ‘Oriole’, both with wild-type versions of all four carotenogenic enzymes, no transcripts for Ccs were detected and no red pigments accumulated. Finally, in a third case, the orange-coloured cultivar, Canary, transcripts for all four of the wild-type carotenogenic enzymes were readily detected yet no CCS protein appeared to accumulate and no red carotenoids were synthesized. In the past, mutations in Psy and Ccs have been identified as the loci controlling colour in the fruit. Now there is evidence that a non-structural gene may control colour development in Capsicum.
Rodriguez-Uribe, Laura; Guzman, Ivette; Rajapakse, Wathsala; Richins, Richard D.; O'Connell, Mary A.
The pericarp of Capsicum fruit is a rich dietary source of carotenoids. Accumulation of these compounds may be controlled, in part, by gene transcription of biosynthetic enzymes. The carotenoid composition in a number of orange-coloured C. annuum cultivars was determined using HPLC and compared with transcript abundances for four carotenogenic enzymes, Psy, LcyB, CrtZ-2, and Ccs determined by qRT-PCR. There were unique carotenoid profiles as well as distinct patterns of transcription of carotenogenic enzymes within the seven orange-coloured cultivars. In one cultivar, 'Fogo', carrying the mutant ccs-3 allele, transcripts were detected for this gene, but no CCS protein accumulated. The premature stop termination in ccs-3 prevented expression of the biosynthetic activity to synthesize the capsanthin and capsorubin forms of carotenoids. In two other orange-coloured cultivars, 'Orange Grande' and 'Oriole', both with wild-type versions of all four carotenogenic enzymes, no transcripts for Ccs were detected and no red pigments accumulated. Finally, in a third case, the orange-coloured cultivar, Canary, transcripts for all four of the wild-type carotenogenic enzymes were readily detected yet no CCS protein appeared to accumulate and no red carotenoids were synthesized. In the past, mutations in Psy and Ccs have been identified as the loci controlling colour in the fruit. Now there is evidence that a non-structural gene may control colour development in Capsicum. PMID:21948863
Rodriguez-Uribe, Laura; Guzman, Ivette; Rajapakse, Wathsala; Richins, Richard D; O'Connell, Mary A
Background To determine level, variability and functional annotation of gene expression of the human retinal pigment epithelium (RPE), the key tissue involved in retinal diseases like age-related macular degeneration and retinitis pigmentosa. Macular RPE cells from six selected healthy human donor eyes (aged 63–78 years) were laser dissected and used for 22k microarray studies (Agilent technologies). Data were analyzed with Rosetta Resolver, the web tool DAVID and Ingenuity software. Results In total, we identified 19,746 array entries with significant expression in the RPE. Gene expression was analyzed according to expression levels, interindividual variability and functionality. A group of highly (n = 2,194) expressed RPE genes showed an overrepresentation of genes of the oxidative phosphorylation, ATP synthesis and ribosome pathways. In the group of moderately expressed genes (n = 8,776) genes of the phosphatidylinositol signaling system and aminosugars metabolism were overrepresented. As expected, the top 10 percent (n = 2,194) of genes with the highest interindividual differences in expression showed functional overrepresentation of the complement cascade, essential in inflammation in age-related macular degeneration, and other signaling pathways. Surprisingly, this same category also includes the genes involved in Bruch's membrane (BM) composition. Among the top 10 percent of genes with low interindividual differences, there was an overrepresentation of genes involved in local glycosaminoglycan turnover. Conclusion Our study expands current knowledge of the RPE transcriptome by assigning new genes, and adding data about expression level and interindividual variation. Functional annotation suggests that the RPE has high levels of protein synthesis, strong energy demands, and is exposed to high levels of oxidative stress and a variable degree of inflammation. Our data sheds new light on the molecular composition of BM, adjacent to the RPE, and is useful for candidate retinal disease gene identification or gene dose-dependent therapeutic studies.
Booij, Judith C; van Soest, Simone; Swagemakers, Sigrid MA; Essing, Anke HW; Verkerk, Annemieke JMH; van der Spek, Peter J; Gorgels, Theo GMF; Bergen, Arthur AB
· Background: At present no satisfying treatment for subfoveal choroidal neovascularization (CNV) secondary to age-related\\u000a macular degeneration (AMD) is available. Visual results after successful surgical removal of subfoveal CNV are disappointing.\\u000a This has been explained by a primary dysfunction of the retinal pigment epithelium (RPE) in the macular region and the surgical\\u000a trauma to the RPE in patients with AMD.
Sebastian Wolf; Alexandra Lappas; Andreas W. A. Weinberger; Bernd Kirchhof
We review the epidemiology, pathophysiology, and etiology of cystoid macular edema (CME). Inflammatory, diabetic, post-cataract, and macular edema due to age-related macular degeneration is described. The role of chronic inflammation and hypoxia and direct macular traction is evaluated in each case according to different views from the literature. The different diagnostic methods for evaluating the edema are described. Special attention is given to fluoroangiography and the most modern methods of macula examination, such as ocular coherence tomography and multifocal electroretinography. Finally, we discuss the treatment of cystoid macular edema in relation to its etiology. In this chapter we briefly refer to the therapeutic value of laser treatment especially in diabetic maculopathy or vitrectomy in some selected cases. Our paper is focused mainly on recent therapeutic treatment with intravitreal injection of triamcinolone acetonide and anti-VEGF factors like bevacizumab (Avastin), ranibizumab (Lucentis), pegaptamid (Macugen), and others. The goal of this paper is to review the current status of this treatment for macular edema due to diabetic maculopathy, central retinal vein occlusion and post-cataract surgery. For this reason the results of recent multicenter clinical trials are quoted, as also our experience on the use of intravitreal injections of anti-VEGF factors and we discuss its value in clinical practice.
Rotsos, Tryfon G; Moschos, Marilita M
The present invention relates to pearlescent pigments based on substrates coated with one or more layers of nitrides or oxynitrides to a method for the production of such pigments and their use in plastics, paints, coatings, powder coatings, inks, printing inks, glasses, ceramic products, agriculture foils, for lasermarking of papers and plastics, security applications and in cosmetic formulations.
Background: Diffuse hyperpigmentation is common among patients with chronic renal failure undergoing hemodialysis (HD). We have examined serum levels of 5-S-cysteinyldopa (5SCD, a pheomelanin precursor), pheomelanin, eumelanin, and protein-bound (PB-) 3,4-dihydroxyphenylalanine (DOPA) and PB-5SCD in HD patients. Methods: Pheomelanin and eumelanin were assayed by chemical degradation methods. Results: Serum levels of free 5SCD in HD patients (n = 16) were
Kazutaka Murakami; Kazumasa Wakamatsu; Yukiko Nakanishi; Hiroki Takahashi; Satoshi Sugiyama; Shosuke Ito
Background Mitochondrial dysfunction is associated with the development and progression of age-related macular degeneration (AMD). Recent studies using populations from the United States and Australia have demonstrated that AMD is associated with mitochondrial (mt) DNA haplogroups (as defined by combinations of mtDNA polymorphisms) that represent Northern European Caucasians. The aim of this study was to use the cytoplasmic hybrid (cybrid) model to investigate the molecular and biological functional consequences that occur when comparing the mtDNA H haplogroup (protective for AMD) versus J haplogroup (high risk for AMD). Methodology/Principal Findings Cybrids were created by introducing mitochondria from individuals with either H or J haplogroups into a human retinal epithelial cell line (ARPE-19) that was devoid of mitochondrial DNA (Rho0). In cybrid lines, all of the cells carry the same nuclear genes but vary in mtDNA content. The J cybrids had significantly lower levels of ATP and reactive oxygen/nitrogen species production, but increased lactate levels and rates of growth. Q-PCR analyses showed J cybrids had decreased expressions for CFH, C3, and EFEMP1 genes, high risk genes for AMD, and higher expression for MYO7A, a gene associated with retinal degeneration in Usher type IB syndrome. The H and J cybrids also have comparatively altered expression of nuclear genes involved in pathways for cell signaling, inflammation, and metabolism. Conclusion/Significance Our findings demonstrate that mtDNA haplogroup variants mediate not only energy production and cell growth, but also cell signaling for major molecular pathways. These data support the hypothesis that mtDNA variants play important roles in numerous cellular functions and disease processes, including AMD.
Kenney, M. Cristina; Chwa, Marilyn; Atilano, Shari R.; Pavlis, Janelle M.; Falatoonzadeh, Payam; Ramirez, Claudio; Malik, Deepika; Hsu, Tiffany; Woo, Grace; Soe, Kyaw; Nesburn, Anthony B.; Boyer, David S.; Kuppermann, Baruch D.; Jazwinski, S. Michal; Miceli, Michael V.; Wallace, Douglas C.; Udar, Nitin
Leafy vegetables are important sources of dietary carotenoids and rank highest for reported lutein concentrations. We have shown previously that lutein concentrations can range from 4.8 to 13.4 mg\\/100 g fresh weight (FW) for kale (Brassica oleracea L.), from 6.5 to 13.0 mg\\/100 g FW for spinach (Spinacia oleracea L.), and from 4.1 to 8.3 mg\\/100 g FW for basil
Dean A. Kopsell; D. E. Kopsell; J. Curran-Celentano; A. J. Wenzel
Purpose To correlate the clinical and histopathologic features of Best vitelliform macular dystrophy (BVMD). Methods Two eyes were obtained postmortem from a patient with BVMD. The patient’s clinical information was reviewed. Series sections of the globes were performed and sequentially stained with hematoxylin-eosin, periodic acid-Schiff or Masson trichrome. A section of the left macula was submitted for electron microscopic processing. Histopathologic findings were reconstructed in a scaled two-dimensional map and compared with fundus photography, fundus autofluorescence (FAF), fundus fluorescein angiography (FFA) and optical coherence tomography (OCT) images. Results The macular lesion of the right eye was identified as a well-demarcated region with pigment, elevated submacular yellow material and subretinal fluid. This corresponded histopathologically to a well-circumscribed area of RPE hyperplasia, accumulation of lipofuscin in the RPE, deposition of granular material in the photoreceptors, macrophages and drusen. The left eye displayed a 1 disc diameter chorioretinal scar with surrounding shallow fluid and submacular pigment. This corresponded to RPE changes and a fibrocellular proliferation in the choriocapillaris. Conclusion Histopathologic mapping revealed retinal edema, RPE abnormalities, drusen and a chorioretinal scar in BVMD that correlated with the fundus, FFA, FAF and OCT findings.
Zhang, Qing; Small, Kent W.
Low concentrations of pyocyanin are reported to enhance superoxide production by human neutrophils exposed to various stimuli, yet the mechanism remains unknown. Using lucigenin-enhanced chemiluminescence, we examined the kinetics of the neutrophil superoxide response in the presence of pyocyanin. At all concentrations (12.5 to 200 microM), pyocyanin decreased the peak superoxide response while prolonging the duration of the response. The prolonged response may be associated with an observed increase in intracellular diacylglyceride levels due to pyocyanin exposure.
Muller, M; Sorrell, T C
Trace elements might play a role in the complex multifactorial pathogenesis of age-related macular degeneration (AMD). The aim of this study was to measure alterations of trace elements levels in aqueous humor of patients with non-exsudative (dry) AMD. For this pilot study, aqueous humor samples were collected from patients undergoing cataract surgery. 12 patients with dry AMD (age 77.9±6.62, female 8, male 4) and 11 patients without AMD (age 66.6±16.7, female 7, male 4) were included. Aqueous levels of cadmium, cobalt, copper, iron, manganese, selenium, and zinc were measured by use of Flow-Injection-Inductively-Coupled-Plasma-Mass-Spectrometry (FI-ICP-MS), quality controlled with certified standards. Patients with AMD had significantly higher aqueous humor levels of cadmium (median: 0.70 µmol/L, IQR: 0.40–0.84 vs. 0.06 µmol/L; IQR: 0.01–.018; p?=?0.002), cobalt (median: 3.1 µmol/L, IQR: 2.62–3.15 vs. 1.17 µmol/L; IQR: 0.95–1.27; p<0.001), iron (median: 311 µmol/L, IQR: 289–329 vs. 129 µmol/L; IQR: 111–145; p<0.001) and zinc (median: 23.1 µmol/L, IQR: 12.9–32.6 vs. 5.1 µmol/L; IQR: 4.4–9.4; p?=?0.020) when compared with patients without AMD. Copper levels were significantly reduced in patients with AMD (median: 16.2 µmol/L, IQR: 11.4–31.3 vs. 49.9 µmol/L; IQR: 32.0–.142.0; p?=?0.022) when compared to those without. No significant differences were observed in aqueous humor levels of manganese and selenium between patients with and without AMD. After an adjustment for multiple testing, cadmium, cobalt, copper and iron remained a significant factor in GLM models (adjusted for age and gender of the patients) for AMD. Alterations of trace element levels support the hypothesis that cadmium, cobalt, iron, and copper are involved in the pathogenesis of AMD.
Junemann, Anselm G. M.; Stopa, Piotr; Michalke, Bernhard; Chaudhri, Anwar; Reulbach, Udo; Huchzermeyer, Cord; Schlotzer-Schrehardt, Ursula; Kruse, Friedrich E.; Zrenner, Eberhart; Rejdak, Robert
PURPOSE: To report a case of retinal pigment epithelial tear after photodynamic therapy for choroidal neovascularization.METHODS: Case report. A 74-year-old woman with exudative age-related macular degeneration and classic subfoveal choroidal neovascularization RE underwent photodynamic therapy with verteporfin.RESULTS: Ophthalmoscopy and fluorescein angiography RE disclosed a retinal pigment epithelial tear in the area of photodynamic therapy.CONCLUSION: This case presents the first report
Faik Gelisken; Werner Inhoffen; Michael Partsch; Ulrike Schneider; Ingrid Kreissig
Background Pigment epithelium-derived factor (PEDF) has been proved to be closely correlated with metabolic syndrome (MetS) and its components that are all risk factors of cardiovascular disease and may play a protective role against vascular injury and atherosclerosis. The present study was designed to investigate the relationship between serum PEDF and coronary artery disease (CAD). Methods A total of 312 consecutive in-patients (including 228 with CAD and 197 with MetS) who underwent coronary angiography were enrolled. Serum PEDF was measured by sandwich enzyme immunoassay and used to carry out multivariate stepwise regression analysis to assess correlation with patient demographic and clinical parameters. Multiple logistic regression analysis was performed to identify factors independently correlated with CAD. Results Patients with MetS had significantly higher levels of serum PEDF than non-MetS subjects (11.1(8.2, 14.2) vs. 10.1(7.6, 12.4) ?g/mL; P?0.05). Patients with CAD also had significantly higher serum PEDF than non-CAD subjects (11.0(8.1, 14.2) vs. 10.3(8.1, 12.8) ?g/mL; P?0.05). Triglyceride (TG), C-reactive protein (CRP), estimated glomerular filtration rate (eGFR), and hypoglycemic therapy were independently correlated with serum PEDF levels, and serum PEDF was independently positively correlated with CAD. Conclusions Serum PEDF levels are independently positively associated with CAD in a Chinese population. Elevated PEDF may act as a protective response against vascular damage and subsequent CAD.
Purpose Age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) are the leading causes of vision loss in the elderly Asian population. Previous studies have confirmed that abnormal extracellular matrix (ECM) metabolism plays an important role in the pathogenesis of AMD and PCV. However, the dynamic metabolism of the ECM is closely regulated by matrix metalloproteinases (MMPs) and tissue metalloproteinase inhibitors (TIMPs). Whether MMPs and TIMPs participate in the pathogenesis of AMD and PCV remains unclear. The aim of this study was to investigate the correlation between circulating MMP and TIMP levels and AMD and PCV. Methods The serum levels of MMPs (MMP1, MMP2, MMP3, and MMP9) and TIMPs (TIMP1 and TIMP3) were quantified using enzyme-linked immunosorbent assays in four groups of subjects (n=342): early AMD (group 1, n=75), neovascular AMD (group 2, n=89), PCV (group 3, n=98), and age- and gender-matched controls (group 4, n=80). Results The mean concentrations of the two gelatinases, MMP2 and MMP9, in the PCV group were significantly higher than that of the control (p=0.001, p<0.001, respectively), early AMD (both p<0.001), and neovascular AMD (p=0.005, p=0.001, respectively) groups. Moreover, the serum MMP2 concentration was positively correlated with the serum MMP9 concentration in the PCV group (r=0.822, p<0.001). However, the mean concentrations of MMP2 and MMP9 in the early AMD and neovascular AMD groups were not significantly different from that of the control group (p>0.05). The mean serum levels of MMP1, MMP3, TIMP1, and TIMP3 were not significantly different among the four groups. Conclusions This pilot study first reveals a link between increased levels of circulating gelatinases (MMP2 and MMP9) and PCV but not AMD, which may provide a biologically relevant marker of ECM metabolism in patients with PCV. This finding suggests that the two disorders may have different molecular mechanisms.
Zeng, Renpan; Zhang, Xiongze; Su, Yu
We mapped a new X-linked recessive atrophic macular degeneration locus to Xp21.1-p11.4 and show allelic involvement of the gene RPGR, which normally causes severe peripheral retinal degeneration leading to global blindness. Ten affected males whom we examined had primarily macular atrophy causing progressive loss of visual acuity with minimal peripheral visual impairment. One additional male showed extensive macular degeneration plus peripheral loss of retinal pigment epithelium and choriocapillaries. Full-field electroretinograms (ERGs) showed normal cone and rod responses in some affected males despite advanced macular degeneration, emphasizing the dissociation of atrophic macular degeneration from generalized cone degenerations, including X-linked cone dystrophy (COD1). The RPGR gene nonsense mutation G-->T at open reading frame (ORF)15+1164 cosegregated with the disease and may create a donor splice site. Identification of an RPGR mutation in atrophic maculardegeneration expands the phenotypic range associated with this gene and provides a new tool for the dissection of the relationship between clinically different retinal pathologies. PMID:12160730
Ayyagari, Radha; Demirci, F Yesim; Liu, Jiafan; Bingham, Eve L; Stringham, Heather; Kakuk, Laura E; Boehnke, Michael; Gorin, Michael B; Richards, Julia E; Sieving, Paul A
Fossil pigments often preserve in lake sediments long after the morphological remains of most algae and bacteria are lost.\\u000a In principle, analyses of sedimentary carotenoids, chlorophylls, their derivatives and other lipid-soluble pigments can be\\u000a used to reconstruct historical changes in primary-producer community abundance and composition, so long as biomarkers are\\u000a accurately isolated, identified and quantified. This chapter summarizes a series
Peter R. Leavitt; Dominic A. Hodgson
PURPOSE. The authors previously published the novel finding that iron regulates L-glutamate synthesis and accumulation in the cell-conditioned medium (CCM) by increasing cytosolic aconitase activity in cultured lens epithelial cells (LECs), retinal pigment epithelial (RPE) cells, and neurons. The present study was designed to determine whether iron-induced L-glutamate accumulation in the CCM regulates L-cystine uptake and gluta- thione (GSH) levels
Marilyn M. Lall; Jenny Ferrell; Steve Nagar; Lloyd N. Fleisher; M. Christine McGahan
We propose a generic pigment model suitable for digital painting in a wide range of genres including traditional Chinese painting and water-based painting. The model embodies a simulation of the pigment-water solution and its interaction with the brush and the paper at the level of pigment particles; such a level of detail is needed for achieving highly intricate effects by
Songhua Xu; Haisheng Tan; Xiantao Jiao; Francis C. M. Lau; Yunhe Pan
A large number of non-pigmented Staphylococcus chromogenes were isolated from the skin of piglets with exudative epidermitis and healthy pigs. Their characteristics were homologous with S. chromogenes type strain, except for pigment production. Strains of non-pigmented S. chromogenes exhibited high levels of DNA homology with S. chromogenes type strain. The colony morphology and pigmentation of non-pigmented S. chromogenes was very similar to S. hyicus type strain, but their characteristics differ in hyaluronidase production, heat stable DNase, Tween 80 hydrolysis and bacitracin resistance. Further, DNA homology drew a distinction between non-pigmented S. chromogenes and S. hyicus type strain. PMID:8844615
Saito, K; Higuchi, T; Kurata, A; Fukuyasu, T; Ashida, K
The influence of varied concentrations of sucrose and ammonical (NH4+) nitrogen on in vitro induction and expression of anthocyanin pigments from Rosa hybrida cv. ‘Pusa Ajay’ was investigated. Of two explants (petal and leaf discs) selected and cultured under two different conditions\\u000a (light and dark), leaf discs were found to be most suitable for callus initiation. Profuse and early callus induction
Mohan Ram; K. V. Prasad; Charanjit Kaur; S. K. Singh; Ajay Arora; Surendra Kumar
Purpose: The effect of vitreopapillary adhesion (VPA) in macular diseases is not understood. Spectral-domain optical coherence tomography/scanning laser ophthalmoscopy (SD-OCT/SLO) was used to identify VPA in macular holes, lamellar holes, macular pucker, and dry age-related macular degeneration (AMD). Methods: Ultrasonography and SD-OCT/SLO were performed in 99 subjects: 17 with macular holes, 11 with lamellar holes, 28 with macular pucker, 15 with dry AMD, and 28 age-matched controls. Outcome measures were the presence of total posterior vitreous detachment (PVD) by ultrasound and the presence or absence of VPA and intraretinal cystoid spaces by SD-OCT/SLO. Results: PVD was detected by ultrasound in 26 (92.9%) of 28 eyes with macular pucker, 6 (54.5%) of 11 eyes with lamellar holes (P = .01), and 4 (23.5%) of 17 eyes with macular holes (P = .000003). SD-OCT/SLO detected VPA in 15 (88.2%) of 17 eyes with macular holes, 11 (39.3%) of 28 age-matched controls (P = .002), 4 (36.4%) of 11 eyes with lamellar holes (P = .01), 4 (26.7%) of 15 eyes with dry AMD (P = .0008), and 5 (17.9%) of 28 eyes with macular pucker (P = .000005). Intraretinal cystoid spaces were present in 15 (100%) of 15 eyes with macular holes with VPA. In eyes with macular pucker, 4 (80%) of 5 with VPA had intraretinal cystoid spaces, but only 1 (4.3%) of 23 without VPA had intraretinal cystoid spaces (P = .001). Conclusions: VPA was significantly more common in eyes with macular holes than in controls or eyes with dry AMD, lamellar holes, or macular pucker. Intraretinal cystoid spaces were found in all eyes with macular holes with VPA. When present in macular pucker, VPA was frequently associated with intraretinal cystoid spaces. Although these investigations do not study causation directly, VPA may have an important influence on the vectors of force at the vitreoretinal interface inducing cystoid spaces and holes.
Sebag, J.; Wang, Michelle Y.; Nguyen, Dieuthu; Sadun, Alfredo A.
The adaptive function of melanin-based coloration is a long-standing debate. A recent genetic model suggested that pleiotropy could account for covariations between pigmentation, behaviour, morphology, physiology and life history traits. We explored whether the expression levels of genes belonging to the melanocortin system (MC1R, POMC, PC1/3, PC2 and the antagonist ASIP), which have many pleiotropic effects, are associated with melanogenesis (through variation in the expression of the genes MITF, SLC7A11, TYR, TYRP1) and in turn melanin-based coloration. We considered the tawny owl (Strix aluco) because individuals vary continuously from light to dark reddish, and thus, colour variation is likely to stem from differences in the levels of gene expression. We measured gene expression in feather bases collected in nestlings at the time of melanin production. As expected, the melanocortin system was associated with the expression of melanogenic genes and pigmentation. Offspring of darker reddish fathers expressed PC1/3 to lower levels but tended to express PC2 to higher levels. The convertase enzyme PC1/3 cleaves the POMC prohormone to obtain ACTH, while the convertase enzyme PC2 cleaves ACTH to produce ?-melanin-stimulating hormone (?-MSH). ACTH regulates glucocorticoids, hormones that modulate stress responses, while ?-MSH induces eumelanogenesis. We therefore conclude that the melanocortin system, through the convertase enzymes PC1/3 and PC2, may account for part of the interindividual variation in melanin-based coloration in nestling tawny owls. Pleiotropy may thus account for the covariation between phenotypic traits involved in social interactions (here pigmentation) and life history, morphology, behaviour and physiology. PMID:24033481
Emaresi, Guillaume; Ducrest, Anne-Lyse; Bize, Pierre; Richter, Hannes; Simon, Celine; Roulin, Alexandre
Immune function can be modulated by multiple physiological factors, including nutrition and reproductive state. Because these factors can vary throughout an individual's lifetime as a result of environmental conditions (affecting nutrition) or life-history stage (e.g. entering the adult reproduction stage), we must carefully examine the degree to which developmental versus adult conditions shape performance of the immune system. We investigated how variation in dietary access to carotenoid pigments - a class of molecules with immunostimulatory properties that females deposit into egg yolks - during three different developmental time points affected adult immunological and reproductive traits in female mallard ducks (Anas platyrhynchos). In males and females of other avian species, carotenoid access during development affects carotenoid assimilation ability, adult sexual ornamentation and immune function, while carotenoid access during adulthood can increase immune response and reproductive investment (e.g. egg-laying capacity, biliverdin deposition in eggshells). We failed to detect effects of developmental carotenoid supplementation on adult immune function [phytohemagglutinin-induced cutaneous immune response, antibody production in response to the novel antigen keyhole limpet hemocyanin (KLH), or oxidative burst, assessed by changes in circulating nitric oxide levels], carotenoid-pigmented beak coloration, ovarian development, circulating carotenoid levels or concentration of bile pigments in the gall bladder. However, we did uncover positive relationships between circulating carotenoid levels during adulthood and KLH-specific antibody production, and a negative relationship between biliverdin concentration in bile and KLH-specific antibody production. These results are consistent with the view that adult physiological parameters better predict current immune function than do developmental conditions, and highlight a possible, previously unstudied relationship between biliverdin and immune system performance. PMID:23531827
Butler, Michael W; McGraw, Kevin J
Age-related macular degeneration (AMD) is an ocular disease that causes damage to the retinal macula, mostly in the elderly. Normal aging processes can lead to structural and blood flow changes that can predispose patients to AMD, although advanced age does not inevitably cause AMD. In this review, we describe changes that occur in the macular structure, such as the retinal pigment epithelium and Bruch’s membrane, with advancing age and in AMD. The role of genetics in AMD and age-related changes in ocular blood flow that may play a role in the pathogenesis of AMD are also discussed. Understanding the pathophysiology of AMD development can help guide future research to further comprehend this disease and to develop better treatments to prevent its irreversible central vision loss in the elderly.
Ehrlich, Rita; Harris, Alon; Kheradiya, Nisha S; Winston, Diana M; Ciulla, Thomas A; Wirostko, Barbara
The current treatment of macular oedema remains unsatisfactory. The dissection of the molecular mechanisms responsible for\\u000a the formation of macular oedema will lead to the identification of specific therapeutic targets, and the successful application\\u000a of this knowledge will result in the generation of more effective treatment modalities.
Antonia M. Joussen; Bernd Kirchhof
The composition and content of secondary compounds produced by the shikimate pathway and the contents of protein and cellulose were determined in leaves of amaranth (Amaranthus tricolor L.) K-99 and the cultivar Valentina raised from it by family selection and enriched in the pigment amaranthine. It was found that intense biosynthesis of amaranthine, tyrosine, and phenylalanine resulted in a decrease in the contents of lignin, protein, and cellulose in leaves of Valentina by comparison with K-99 and in changed the morphological traits: color deepening and a decrease in leaf density. It is concluded that amaranth biosynthesis is related to nitrogen metabolism and amaranthine is an intermediate involved in conversion of nitrogen compounds in the cell. PMID:12391759
Gins, M S; Gins, V K; Kononkov, P F
Background Vitamin D plays a critical role in bone metabolism and many cellular and immunological processes. Recent research indicates that concentrations of serum 25-hydroxyvitamin D [25(OH)D], the main indicator of vitamin D status, should be in excess of 75 nmol/L. Low levels of 25(OH)D have been associated with several chronic and infectious diseases. Previous studies have reported that many otherwise healthy adults of European ancestry living in Canada have low vitamin D concentrations during the wintertime. However, those of non-European ancestry are at a higher risk of having low vitamin D levels. The main goal of this study was to examine the vitamin D status and vitamin D intake of young Canadian adults of diverse ancestry during the winter months. Methods One hundred and seven (107) healthy young adults self-reporting their ancestry were recruited for this study. Each participant was tested for serum 25(OH)D concentrations and related biochemistry, skin pigmentation indices and basic anthropometric measures. A seven-day food diary was used to assess their vitamin D intake. An ANOVA was used to test for significant differences in the variables among groups of different ancestry. Linear regression was employed to assess the impact of relevant variables on serum 25(OH)D concentrations. Results More than 93% of the total sample had concentrations below 75 nmol/L. Almost three-quarters of the subjects had concentrations below 50 nmol/L. There were significant differences in serum 25(OH)D levels (p < 0.001) and vitamin D intake (p = 0.034) between population groups. Only the European group had a mean vitamin D intake exceeding the current Recommended Adequate Intake (RAI = 200 IU/day). Total vitamin D intake (from diet and supplements) was significantly associated with 25(OH)D levels (p < 0.001). Skin pigmentation, assessed by measuring skin melanin content, showed an inverse relationship with serum 25(OH)D (p = 0.033). Conclusion We observe that low vitamin D levels are more prevalent in our sample of young healthy adults than previously reported, particularly amongst those of non-European ancestry. Major factors influencing 25(OH)D levels were vitamin D intake and skin pigmentation. These data suggest a need to increase vitamin D intake either through improved fortification and/or supplementation.
Gozdzik, Agnes; Barta, Jodi Lynn; Wu, Hongyu; Wagner, Dennis; Cole, David E; Vieth, Reinhold; Whiting, Susan; Parra, Esteban J
Macular edema constitutes a serious pathologic entity of ophthalmology resulting in vision loss with a remarkable impact on the quality of life of patients. It is the final common pathway of various systemic diseases and underlying intraocular conditions, with diabetes mellitus being the most frequent cause. Other causes include venous occlusive disease, intraocular surgery, and inflammatory conditions of the posterior segment of the eye. Macular edema is a recognized side effect of various systemic and local medications and requires special consideration among ophthalmologists and other clinicians. Recently, antidiabetic thiazolidinediones have been implicated in the development of macular edema, and a review of the English literature revealed that other systemically administered drugs like fingolimod, recently approved for relapsing forms of multiple sclerosis, the anticancer agents tamoxifen and the taxanes, as well as niacin and interferons have been reported to cause macular edema. Ophthalmologic pharmaceutical agents, like prostaglandin analogs, epinephrine, timolol, and ophthalmic preparation preservatives have also been reported to cause macular edema as an adverse event. The purpose of this article is to provide a short, balanced overview of the available evidence in this regard. The available data and the possible pathophysiologic mechanisms leading to the development of macular edema are discussed. Possible therapeutic strategies for drug-induced macular edema are also proposed. PMID:23640687
Makri, Olga E; Georgalas, Ilias; Georgakopoulos, Constantine D
Monascus pigments (MPs) as natural food colorants have been widely utilized in food industries in the world, especially in China and Japan. Moreover, MPs possess a range of biological activities, such as anti-mutagenic and anticancer properties, antimicrobial activities, potential anti-obesity activities, and so on. So, in the past two decades, more and more attention has been paid to MPs. Up to now, more than 50 MPs have been identified and studied. However, there have been some reviews about red fermented rice and the secondary metabolites produced by Monascus, but no monograph or review of MPs has been published. This review covers the categories and structures, biosynthetic pathway, production, properties, detection methods, functions, and molecular biology of MPs. PMID:23104643
Feng, Yanli; Shao, Yanchun; Chen, Fusheng
The retinal pigment epithelial cell (RPE cell) layer protects the photoreceptors of the retina against oxidative stress. The decline of this capacity is believed to be a major factor in the impairment of vision in age-related macular degeneration. Exposure of human adult RPE cells to UV light at predominantly 320-400 nm (UVA light) in the presence of all-trans-retinaldehyde results in photooxidative cytotoxicity. Significant protection of RPE cells was obtained by prior treatment with phase 2 gene inducers, such as the isothiocyanate sulforaphane or a bis-2-hydroxybenzylideneacetone Michael reaction acceptor. The degree of protection was correlated with the potencies of these inducers in elevating cytoprotective glutathione levels and activities of NAD(P)H:quinone oxidoreductase. In embryonic fibroblasts derived from mice in which the genes for the transcription factor Nrf2, the repressor Keap1, or both Nrf2 and Keap1 were disrupted, the magnitude of resistance to photooxidative damage paralleled the basal levels of glutathione and NAD(P)H:quinone oxidoreductase in each cell type. Demonstration of protection of RPE cells against photooxidative damage by induction of phase 2 proteins may shed light on the role of oxidative injury in ocular disease. Moreover, the finding that dietary inducers provide indirect antioxidant protection suggests novel strategies for preventing chronic degenerative diseases, such as age-related macular degeneration. PMID:15229324
Gao, Xiangqun; Talalay, Paul
Fundus autofluorescence imaging is an imaging method that provides additional information compared to conventional imaging techniques. It permits to topographically map lipofuscin distribution of the retinal pigment epithelial cell monolayer. Excessive accumulation of lipofuscin granules in the lysosomal compartment of retinal pigment epithelium cells represents a common downstream pathogenetic pathway in various hereditary and complex retinal diseases including age-related macular degeneration (AMD). This comprehensive review contains an introduction in fundus autofluorescence imaging, including basic considerations, the origin of the signal, different imaging methods, and a brief overview of fundus autofluorescence findings in normal subjects. Furthermore, it summarizes cross-sectional and longitudinal fundus autofluorescence findings in patients with AMD, addresses the pathophysiological significance of increased fundus autofluorescence, and characterizes different fundus autofluorescence phenotypes as well as fundus autofluorescence alterations with disease progression. PMID:19171212
Schmitz-Valckenberg, Steffen; Fleckenstein, Monika; Scholl, Hendrik P N; Holz, Frank G
Background To assess the efficacy, clinical outcomes, visual acuity (VA), incidence of adverse effects, and complications of peripheral iris fixation of 3-piece acrylic IOLs in eyes lacking capsular support. Thirteen patients who underwent implantation and peripheral iris fixation of a 3-piece foldable acrylic PC IOL for aphakia in the absence of capsular support were followed after surgery. Clinical outcomes and macular SD-OCT (Cirrus OCT; Carl Zeiss Meditec, Germany) were analyzed. Findings The final CDVA was 20/40 or better in 8 eyes (62%), 20/60 or better in 12 eyes (92%), and one case of 20/80 due to corneal astigmatism and mild persistent edema. No intraoperative complications were reported. There were seven cases of medically controlled ocular hypertension after surgery due to the presence of viscoelastic in the AC. There were no cases of cystoid macular edema, chronic iridocyclitis, IOL subluxation, pigment dispersion, or glaucoma. Macular edema did not develop in any case by means of SD-OCT. Conclusions We think that this technique for iris suture fixation provides safe and effective results. Patients had substantial improvements in UDVA and CDVA. This surgical strategy may be individualized however; age, cornea status, angle structures, iris anatomy, and glaucoma are important considerations in selecting candidates for an appropriate IOL fixation method.
Background Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the developed countries and is caused by both environmental and genetic factors. A recent study (Tuo et al., PNAS) reported an association between AMD and a single nucleotide polymorphism (SNP) (rs3793784) in the ERCC6 (NM_000124) gene. The risk allele also increased ERCC6 expression. ERCC6 is involved in DNA repair and mutations in ERCC6 cause Cockayne syndrome (CS). Amongst others, photosensitivity and pigmentary retinopathy are hallmarks of CS. Methodology/Principal Findings Separate and combined data from three large AMD case-control studies and a prospective population-based study (The Rotterdam Study) were used to analyse the genetic association between ERCC6 and AMD (2682 AMD cases and 3152 controls). We also measured ERCC6 mRNA levels in retinal pigment epithelium (RPE) cells of healthy and early AMD affected human donor eyes. Rs3793784 conferred a small increase in risk for late AMD in the Dutch population (The Rotterdam and AMRO-NL study), but this was not replicated in two non-European studies (AREDS, Columbia University). In addition, the AMRO-NL study revealed no significant association for 9 other variants spanning ERCC6. Finally, we determined that ERCC6 expression in the human RPE did not depend on rs3793784 genotype, but, interestingly, on AMD status: Early AMD-affected donor eyes had a 50% lower ERCC6 expression than healthy donor eyes (P?=?0.018). Conclusions/Significance Our meta-analysis of four Caucasian cohorts does not replicate the reported association between SNPs in ERCC6 and AMD. Nevertheless, our findings on ERCC6 expression in the RPE suggest that ERCC6 may be functionally involved in AMD. Combining our data with those of the literature, we hypothesize that the AMD-related reduced transcriptional activity of ERCC6 may be caused by diverse, small and heterogeneous genetic and/or environmental determinants.
Bergeron-Sawitzke, Julie; Uitterlinden, Andre G.; Hofman, Albert; van Duijn, Cornelia M.; Merriam, Joanna E.; Smith, R. Theodore; Barile, Gaetano R.; ten Brink, Jacoline B.; Vingerling, Johannes R.; Klaver, Caroline C. W.; Allikmets, Rando; Dean, Michael; Bergen, Arthur A. B.
Background: Transplantation of autologous iris pig- ment epithelium (IPE) into the subretinal space has been suggested as one approach for the treatment of age-re- lated macular degeneration, as well as for other condi- tions in which loss of retinal pigment epithelium (RPE) occurs. Surgical removal of choroidal neovascular mem- branes is associated with traumatic loss of the RPE cell layer,
Gabriele Thumann; Sabine Aisenbrey; Ulrich Schraermeyer; Bart Lafaut; Peter Esser; Peter Walter; Karl Ulrich Bartz-Schmidt
Lutein and zeaxanthin are dietary carotenoids which accumulate in human retina, including the retinal pigment epithelial (RPE) cells. Oxidative damage of RPE cells is involved in the pathogenesis age related macular degeneration (AMD). The purpose of this study was to evaluate the potential protective effect of lutein and zeaxanthin against hydrogen peroxide induced oxidative stress in cultured human RPE cells.
Adela Pintea; Dumitri?a Olivia Rugin?; Raluca Pop; Andrea Bunea; Carmen Socaciu
Retinal pigment epithelium (RPE) transplantation might replace cells lost as a consequence of choroidal neovascular membrane excision in patients with age-related macular degeneration (AMD). Autologous transplantation of RPE cells harvested from a peripheral biopsy may overcome problems of immune rejection. To study the feasibility of autologous RPE cell transplantation, the authors examined the attachment of freshly harvested RPE cells from
I. Tsukahara; S. Ninomiya; A. Castellarin; F. Yagi; I. K. Sugino; M. A. Zarbin
The age related macular degeneration (ARMD) is the most common cause of the central visual acuity loss in persons of age more than 60 years in the well developed countries. Rotation of the macula is nowadays a progressive method of choice of treatment of the exsudative form of ARMD. The aim of this surgical technique is to relocate the neuroretinal epithelium of the central region of the retina to a position situated outside the border of the subfoveolar lesion. Three eyes of three patients (2 woman and one man) were operated on during the period between March and May 2001 at the Department of Ophthalmology of the School of Medicine, Charles University in Pilsen. The method used was the scleral imbrication, which belongs to methods designated as "limited translocation". The mean age of the patients was 62 years and the follow up period was 2 years. After the surgery the relocation of the fovea was observed in all three eyes. In two eyes, the postoperative period was complicated by tractional retinal detachment that occurred three weeks after the surgery as a consequence of progressive proliferative vitreoretinopathy (PVR). Both eyes with the retinal detachment were re-operated. In both of them, the repeated pars plana vitrectomy, epiretinal membranes removal with relaxing retinectomy was performed and after maximal mobilization of the retina, the silicone oil implantation followed. In the second patient, the postoperative period was complicated by elevation of the intraocular pressure and a radial retinal fold running from the encircling buckle indentation up to the macula. Slightly improved function was noticed only in the first patient after following cataract surgery with intraocular lens implantation. In the two other eyes, as noticed at the last follow up check, the postoperative complications caused severe decrease of the central visual acuity although the retina remained attached. Macular translocation procedure is in stage of development and its surgical techniques are being further modified. The risk of postoperative complications with profound loss of central visual acuity corresponds to the level of the technical difficulty and extent of surgical intervention. PMID:15369259
Dolezalová, J; Rusnák, S
Macular telangiectasia type 2-also known as idiopathic perifoveal telangiectasia and juxtafoveolar retinal telangiectasis type 2A or Mac Tel 2-is an acquired bilateral neurodegenerative macular disease that usually manifests itself during the fourth to sixth decades of life and is characterized by minimal dilatation of the parafoveal capillaries with graying of the retinal area involved, a lack of lipid exudation, right-angled retinal venules, refractile deposits in the superficial retina, hyperplasia of the retinal pigment epithelium, foveal atrophy, and subretinal neovascularization (SRNV). Optical coherence tomography images typically demonstrate intraretinal hyporeflective spaces that are usually not related to retinal thickening or fluorescein leakage. The typical fluorescein angiographic finding is a deep intraretinal hyperfluorescent leakage in the temporal parafoveal area. With time the leakage may involve the whole parafovea, but does not extend to the center of the fovea. Long-term prognosis for central vision is variable and depends on the development of SRNV or macular atrophy. Pathogenesis remains unclear, but Müller cells and macular pigment appear to play a central role. Currently there is no known treatment for the underlying cause of this condition, but treatment of the SRNV may be beneficial. PMID:24160729
Wu, Lihteh; Evans, Teodoro; Arevalo, J Fernando
The Macular Photocoagulation Study (MPS) is a set of randomized, controlled clinical trials designed to evaluate the effectiveness of laser photocoagulation of neovascular lesions, secondary to age-related (senile) macular degeneration, ocular histoplasmo...
The Macular Photocoagulation Study (MPS) is a set of randomized, controlled clinical trials designed to evaluate the effectiveness of laser photocoagulation of neovascular lesions, secondary to age-related (senile) macular degeneration (AMD or SMD), ocula...
Abstract Purpose/Aim: The aqueous humor level of soluble vascular endothelial growth factor receptor (sVEGFR)-2 may influence macular edema in patients with branch retinal vein occlusion (BRVO). The association of sVEGFR-2 with macular edema was investigated in this study. Materials and methods: A retrospective case-controlled study was performed in 22 patients with BRVO and macular edema, as well as 5 patients with non-ischemic ocular diseases as the control group. The severity of macular edema was examined by optical coherence tomography. Aqueous humor samples were obtained during intravitreous injection of anti-VEGF agents, triamcinolone acetonide, or combined vitrectomy and cataract surgery. sVEGFR-2 levels in aqueous humor were determined by enzyme-linked immunosorbent assay. Results: The aqueous humor level of sVEGFR-2 (median: 124.5?ng/ml) was significantly elevated in BRVO patients compared with the control group (78.1?pg/ml) (p?=?0.010). In addition, the sVEGFR-2 level was correlated with the severity of macular edema (p?=?0.033). Conclusions: sVEGFR-2 may be involved in the pathogenesis of macular edema associated with BRVO. Measurement of aqueous humor sVEGFR-2 levels may be helpful for understanding the disease status in BRVO patients with macular edema. PMID:23972086
Noma, Hidetaka; Mimura, Tatsuya
Purpose We analyzed the anatomical and visual outcomes after surgical treatment of idiopathic macular holes with pars plana vitrectomy, internal limiting membrane (ILM) peeling using Brilliant Blue dye, and silicone oil tamponade without postoperative posturing. Methods This was a retrospective interventional study of 10 eyes in eight patients who underwent surgical treatment of idiopathic macular holes using pars plana vitrectomy, ILM peeling using Brilliant Blue dye, and silicone oil tamponade without postoperative posturing. The preoperative staging of macular holes and postoperative anatomic outcomes were assessed using spectral-domain optical coherence tomography. Results All patients were women with a mean age of 66.86 ± 4.8 years. In two patients, bilateral macular holes were present and both eyes were operated on. Stage 2 macular hole was diagnosed in three eyes, three eyes had stage 3, and four eyes had stage 4 macular holes. Anatomical success and closure of the macular hole was achieved in nine eyes (90%) after one operation. In one eye, the macular hole was closed after reoperation. The preoperative mean best-corrected visual acuity (BCVA) was 0.15 decimal units (0.8 logMAR units). Until the end of the follow-up period, BCVA was 0.25 decimal units (0.6 logMAR units). Visual acuity was improved in seven patients (70%). In two patients (20%), visual acuity remained at the same level, and in one eye (10%), visual acuity decreased. Postoperatively, all patients reported a significant reduction of metamorphopsia. Conclusion Initial results after 20G pars plana vitrectomy with peeling of the ILM, use of dye (Brilliant Blue), and tamponade with silicone oil without postoperative posturing gave good anatomical and functional outcome in terms of visual acuity and reduction of metamorphopsia. Taking into account the age of the patients, this method, which does not require prolonged postoperative face-down posturing, was well tolerated by the patients. Because the anatomical and visual outcome as well as the rate of postoperative complications are comparable to those when gas is used as a tamponading agent, silicone oil tamponade can also be safely used as a first option in surgery of macular holes. However, a longer period of follow-up of the operated eyes, as well as a larger group of operated eyes, will be required to identify long-term outcomes of this surgical treatment.
Ivanovska-Adjievska, Biljana; Boskurt, Salih; Semiz, Faruk; Yuzer, Hakan; Dimovska-Jordanova, Vesna
Recent histopathologic studies have shown that mitochondria and peroxisomes of the retinal pigment epithelium may play a central role in the pathophysiology of age-related macular degeneration (AMD). We supposed that compounds which improve mitochondrial functions (mitotropic compounds) may show beneficial effects in preventing AMD. Fourteen patients affected by early AMD were treated with a mixture containing acetyl-L-carnitine (ALC), polyunsaturated fatty
J. Feher; A. Papale; G. Mannino; L. Gualdi; C. Balacco Gabrieli
Diabetic macular edema is a major cause of visual impairment. The pathogenesis of macular edema appears to be multifactorial. Laser photocoagulation is the standard of care for macular edema. However, there are cases that are not responsive to laser therapy. Several therapeutic options have been proposed for the treatment of this condition. In this review we discuss several factors and
Neelakshi Bhagat; Ruben A. Grigorian; Arthur Tutela; Marco A. Zarbin
Age-related macular degeneration is a major cause of blindness worldwide. With ageing populations in many countries, more than 20% might have the disorder. Advanced age-related macular degeneration, including neovascular age-related macular degeneration (wet) and geographic atrophy (late dry), is associated with substantial, progressive visual impairment. Major risk factors include cigarette smoking, nutritional factors, cardiovascular diseases, and genetic markers, including genes regulating complement, lipid, angiogenic, and extracellular matrix pathways. Some studies have suggested a declining prevalence of age-related macular degeneration, perhaps due to reduced exposure to modifiable risk factors. Accurate diagnosis combines clinical examination and investigations, including retinal photography, angiography, and optical coherence tomography. Dietary anti-oxidant supplementation slows progression of the disease. Treatment for neovascular age-related macular degeneration incorporates intraocular injections of anti-VEGF agents, occasionally combined with other modalities. Evidence suggests that two commonly used anti-VEGF therapies, ranibizumab and bevacizumab, have similar efficacy, but possible differences in systemic safety are difficult to assess. Future treatments include inhibition of other angiogenic factors, and regenerative and topical therapies. PMID:22559899
Lim, Laurence S; Mitchell, Paul; Seddon, Johanna M; Holz, Frank G; Wong, Tien Y
Age-related macular degeneration is the leading cause of blindness in elderly populations of European descent. The most consistent risk factors associated with this ocular condition are increasing age and cigarette smoking. Genetic investigations have shown that complement factor H, a regulator of the alternative complement pathway, and LOC387715/HtrA1 are the most consistent genetic risk factors for age-related macular degeneration. Although the pathogenesis of this disease is unknown, oxidative stress might have an important role. Treatment with antioxidant vitamins and zinc can reduce the risk of developing advanced age-related macular degeneration by about a quarter in those at least at moderate risk. Intravitreal injections of ranibizumab, a monoclonal antibody that inhibits all forms of vascular endothelial growth factor, have been shown to stabilise loss of vision and, in some cases, improve vision in individuals with neovascular age-related macular degeneration. These findings, combined with assessments of possible environmental and genetic interactions and new approaches to modulate inflammatory pathways, will hopefully further expand our ability to understand and treat age-related macular degeneration.
Coleman, Hanna R; Chan, Chi-Chao; Ferris, Frederick L; Chew, Emily Y
Provided are methods of using levels of markers of systemic inflammation, e.g., CRP, to predict a subject's risk of development or progression of Age-Related Macular Degeneration (AMD), and methods of treating, delaying or preventing the development or pr...
J. M. Seddon
Diabetic macular edema is a major cause of visual impairment. The pathogenesis of macular edema appears to be multifactorial. Laser photocoagulation is the standard of care for macular edema. However, there are cases that are not responsive to laser therapy. Several therapeutic options have been proposed for the treatment of this condition. In this review we discuss several factors and mechanisms implicated in the etiology of macular edema (vasoactive factors, biochemical pathways, anatomical abnormalities). It seems that combined pharmacologic and surgical therapy may be the best approach for the management of macular edema in diabetic patients. PMID:19171208
Bhagat, Neelakshi; Grigorian, Ruben A; Tutela, Arthur; Zarbin, Marco A
Summary We performed a meta-analysis of cross-sectional studies on serum 25(OH)D status globally. Serum 25(OH)D levels on average\\u000a were 54 nmol\\/l, were higher in women than men, and higher in Caucasians than in non-Caucasians. There was no trend in serum\\u000a 25(OH)D level with latitude. Vitamin D deficiency was widespread.\\u000a \\u000a \\u000a \\u000a Introduction We studied vitamin D status (expressed as serum 25-hydroxy-vitamin D [25(OH)D]) in native
T. Hagenau; R. Vest; T. N. Gissel; C. S. Poulsen; M. Erlandsen; L. Mosekilde; P. Vestergaard
Various aspects of painting have long been discussed in the fields of art history and visual culture, but few have taken a close look at the nature of pigments within painting, or in a broader context. This online exhibit looks at the storied history of a number of different pigments, and also looks at the historical perceptions of their respective appearances and nuances. The exhibit begins by looking at pigments in prehistory (such as carbon black), and continues through the eventual discovery of mineral pigments, then the use of synthetic iron oxide pigments. After this introductory section, visitors can browse through a drop-down menu containing a list of over twenty-five pigments, such as Egyptian blue, cadmium yellow, and emerald green. For each pigment, visitors can learn about the history of its use, how the pigment was (or is) made, and its technical details (i.e., its chemical properties). [KMG
The highly radioresistant Rubrobacter radiotolerans, contains red pigments. Since the pigments could not be extracted by usual methods, a new method was developed in which the\\u000a pigments were extracted with organic solvents after addition of 10 N KOH to the intact cells, followed by neutralization.\\u000a These pigments were also extracted after treatment with achromopeptidase, but not with lysozyme. The extracted
T. Saito; H. Terato; O. Yamamoto
Reconstitution and pigment exchange are two experimental techniques that have proven extremely useful to elucidate structure-function\\u000a relationships in chlorophyll (Chl)-protein complexes. In reconstitution experiments the Chl-binding apoproteins, usually in\\u000a their recombinant form, are folded in the presence of pigments to form pigment-protein complexes that are often virtually\\u000a indistinguishable from their native counterparts. Since both the protein and the pigment building
This lesson will examine the two major classes of phototsynthetic pigments, chlorophylls and carotenoids, their biochemical structures and their biosynthesis. The organization of these pigments into photosynthetic pigment, which are protein complexes that harvest light and convert its energy into biochemical energy will be explained.
BACKGROUND: The mechanism by which vitrectomy improves macular edema in patients with branch retinal vein occlusion remains unclear, although intraocular levels of vascular endothelial growth factor have been suggested to influence the visual prognosis and macular edema. METHODS: A series of 54 consecutive patients (54 eyes) with branch retinal vein occlusion was studied prospectively. All patients underwent pars plana vitrectomy
Hidetaka Noma; Hideharu Funatsu; Tatsuya Mimura; Shuichiro Eguchi; Katsunori Shimada
Purpose Iron plays a central role in the oxidative stress caused by hydrogen peroxide. The ubiquitous iron storage protein, ferritin, safely sequesters iron, reducing its ability to cause oxidative damage. Oxidative stress can activate mitogen-activated protein (MAP) kinase pathways with many downstream effects. The purpose of this study was to determine the effects of hydrogen peroxide on MAP kinase pathways (extracellular signal-related kinase [ERK]1/2, c-Jun N-terminal kinase [JNK], and p38) and ferritin levels in canine lens and retinal epithelial cells (lens epithelial cells [LECs] and retinal pigmented epithelial [RPE] cells). Methods Primary cultures of canine LECs and RPE cells were used in these studies. Hydrogen peroxide was delivered either by a single 250 ?M bolus or 0.25 mU/ml glucose oxidase (GO). Immunoblotting was used to determine the activation of the MAP kinase pathways. Ferritin was detected with enzyme immunosorbent assay. Results Baseline activation of ERK1/2 in the untreated RPE cells and LECs was decreased by treatment with U-0126. Bolus hydrogen peroxide greatly increased ERK1/2 activation that had been blocked by U-0126, whereas GO had no significant effect on ERK1/2 phosphorylation. Hydrogen peroxide, either bolus or constant low levels, increased ferritin levels in the LECs and RPE cells. Surprisingly, U-0126 not only did not inhibit the effect of hydrogen peroxide on the ferritin levels but also increased the ferritin levels in both cell types. Neither bolus nor chronic hydrogen peroxide exposure activated the JNK or p38 pathway. Additionally, neither JNK nor p38 inhibitors had any effect on the ferritin concentrations in the LECs or RPE cells. Conclusions Although U-0126 inhibited the hydrogen peroxide–induced increase in ERK1/2 phosphorylation, U-0126’s lack of inhibition of the peroxide-induced increase in intracellular ferritin levels indicates that this pathway is not involved in ferritin induction by hydrogen peroxide. This is the first study to demonstrate that hydrogen peroxide and an inhibitor of ERK1/2 activation can increase the levels of the iron storage protein, ferritin. Since ferritin can shield cells from iron-catalyzed damage, this downstream effect likely plays a protective role, which, in the case of the ERK1/2 inhibitor, U-0126, demonstrates a potential therapeutic target.
Lall, Marilyn M.; Harned, Jill
Diffuse electrical currents delivered to the eye were investigated in a rat model of retinitis pigmentosa for potentially therapeutic effects. Low-level currents were passed between electrodes placed on the cornea and in the mouth during 30-min sessions two times per week from 4 to 16 weeks of age. Single-flash electroretinograms (ERG) were recorded and analyzed for amplitude and measures of sensitivity, and basic histology was performed. ERG a-wave amplitudes were slightly greater in treated vs. age-matched controls at 16 weeks of age, but the combined thicknesses of the outer nuclear layer and outer segment layer were similar at this age. Treated animals exhibited a significant preservation of b-wave amplitudes, and a striking preservation of rod sensitivity, measured as the stimulus strength required to reach half-saturation of the a-wave. Analysis of the leading edge of the a-wave using a delayed Gaussian function revealed a decrease in the parameter reflecting gain of the phototransduction cascade over the 12-week course of treatment, and no significant change in control animals over the same period. These results suggest that while the exogenous currents failed to preserve the number or gross structure of rods, the responsivity of individual photoreceptors was relatively preserved, perhaps via an increase in efficiency of photon capture (R/photon). This preserved functionality may delay the retraction of bipolar cell dendrites from degenerating photoreceptors. PMID:23147691
Rahmani, Safa; Bogdanowicz, Les; Thomas, Joel; Hetling, John R
Purpose. Lipofuscin, a fluorescent lysosomal pigment made of lipophilic molecules, is associated with age-related pathophysiological processes in the retinal pigment epithelium (RPE). The best-characterized components of lipofuscin are A2E and its oxides, but a direct spatial correlation with lipofuscin has not previously been possible. Methods. Lipofuscin fluorescence was mapped across the RPE of Abca4?/? and Sv129 (background strain control) mice. In the same tissues, they determined the spatial distribution of A2E and its oxides by using the high molecular specificity of matrix-assisted laser desorption-ionization imaging mass spectrometry (MALDI-IMS). The fluorescence and tandem mass spectra taken directly from the tissue were compared with those of synthetic A2E standard. Results. In 2-month-old mice, A2E was found in the center of the retinal pigment epithelial tissue; with age, A2E increased across the tissue. With high levels of A2E, there was a marked correlation between A2E and lipofuscin, but with low levels this correlation diminished. The distributions of the oxidized forms of A2E were also determined. The amount of oxidation on A2E remained constant over 6 months, implying that A2E does not become increasingly oxidized with age in this time frame. Conclusions. This report is the first description of the spatial imaging of a specific retinoid from fresh tissue and the first description of a direct correlation of A2E with lipofuscin. The molecule-specific imaging of lipofuscin components from the RPE suggests wide applicability to other small molecules and pharmaceuticals for the molecular characterization and treatment of age-related macular degeneration.
Grey, Angus C.; Crouch, Rosalie K.; Koutalos, Yiannis; Schey, Kevin L.
Choroidal neovascularization (CNV) is a hallmark of age-related macular degeneration (AMD). Angiogenic factors produced by retinal pigment epithelial cells (RPE) are major contributors to CNV development. The ubiquitin-proteasome pathway (UPP) plays critical roles in many cellular processes, such as...
Objective: To determine the prevalence and visual sig- nificance of cystoid macular edema (CME) in eyes with subfoveal neovascular age-related macular degenera- tion using optical coherence tomography (OCT). Materials and Methods: The medical records of 61 consecutive patients initially seen with nondisciform sub- foveal neovascular age-related macular degeneration were retrospectively reviewed. All patients underwent fluo- rescein angiography and OCT imaging.
T. Daniel Ting; Mila Oh; Terry A. Cox; Carsten H. Meyer; Cynthia A. Toth
Physiological stress response and oxidative damage are factors for aging processes and, as such, are thought to contribute to neovascular age-related macular degeneration (AMD). Paraoxonase 1 (PON1) is an enzyme that plays an important role in oxidative stress and aging. We investigated association of DNA sequence variants (SNP) within the upstream regulatory region of the PON1 gene with neovascular AMD in 305 patients and 288 controls. Four of the seven tested SNPs (rs705379, rs705381, rs854573, and rs757158) were more frequently found in AMD patients compared to controls (P?=?0.0099, 0.0295, 0.0121, and 0.0256, respectively), and all but one (SNP rs757158) are in linkage disequilibrium. Furthermore, haplotype TGGCCTC conferred protection (odds ratio (OR)?=?0.76, (CI)?=?0.60-0.97) as it was more frequently found in control individuals, while haplotype CGATGCT increased the risk (OR?=?1.55, CI?=?1.09-2.21) for AMD. These results were also reflected when haplotypes for the untranscribed and the 5'untranslated regions (5'UTR) were analyzed separately. To assess haplotype correlation with levels of gene expression, the three SNPs within the 5'UTR were tested in a luciferase reporter assay. In retinal pigment epithelium-derived ARPE19 cells, we were able to measure significant differences in reporter levels, while this was not observed in kidney-derived HEK293 cells. The presence of the risk allele A (SNP rs705381) caused an increase in luciferase activity of approximately twofold. Our data support the view that inflammatory reactions mediated through anti-oxidative activity may be relevant to neovascular age-related macular degeneration. PMID:22956172
Oczos, Jadwiga; Grimm, Christian; Barthelmes, Daniel; Sutter, Florian; Menghini, Moreno; Kloeckener-Gruissem, Barbara; Berger, Wolfgang
PURPOSE: To describe the characteristics and evolution of macular retinoschisis in high myopia observed by optical coherence tomography (OCT).DESIGN: A consecutive, retrospective, observational case series.METHODS: Twenty-one highly myopic eyes (mean refractive error, ?15.2, range ?6 to ?25) of 17 patients presenting with the unusual feature of macular thickening without a macular hole and associated with a posterior staphyloma were examined
Nathanaël Benhamou; Pascale Massin; Belkacem Haouchine; Ali Erginay; Alain Gaudric
Diabetic macular edema is a leading cause of vision impairment among people within the working- age population. This review discusses the pathogenesis of diabetic macular edema and the treatment options currently available for the treatment of diabetic macular edema, including for focal/grid photocoagulation, intravitreal corticosteroids and intravitreal anti-vascular endothelial growth factor agents. The biologic rationale for novel therapeutic agents, many of which are currently being evaluated in clinical trials, also is reviewed.
Wenick, Adam S.; Bressler, Neil M.
PURPOSE: To correlate postmortem histology from a patient with macular telangiectasia (MacTel) type 2 with previously recorded clinical imaging data. DESIGN: Observational clinicopathologic case report. METHODS: The distribution of retinal blood vessels was used to map the location of serial wax sections in color fundus and optical coherence tomography (OCT) images. Fluorescent immunohistochemistry was used to visualize markers for Müller's cells (vimentin and retinaldehyde-binding protein 1), photoreceptors (L-M opsin, rhodopsin, and cytochrome oxidase 2), and the outer limiting membrane (OLM) (zonula occludens 1 and occludin). MAIN OUTCOME MEASURES: Distribution of specific markers in immunohistochemistry on retinal sections through the fovea in relation to clinical data. RESULTS: The clinically recorded region of macular pigment loss in the macula correlated well with Müller's cell depletion. The OCT data showed a loss of the photoreceptor inner segment/outer segment (IS/OS) junction in the central retina, which correlated well with rod loss but not with cone loss. Markers for the OLM were lost where Müller's cells were lost. CONCLUSIONS: We have confirmed our previous finding of Müller's cell loss in MacTel type 2 and have shown that the area of Müller's cell loss matches the area of macular pigment depletion. In this patient, the IS/OS junction seen by OCT was absent in a region where rods were depleted but cones were still present. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article. PMID:23769334
Powner, Michael B; Gillies, Mark C; Zhu, Meidong; Vevis, Kristis; Hunyor, Alex P; Fruttiger, Marcus
Aims This study investigated the expression and localisation of thrombospondin?1 (TSP?1), a known anti?angiogenic extracellular matrix protein, in normal aged control human eyes and eyes with age related macular degeneration (AMD). Methods Immunohistochemical analysis with mouse anti?human TSP?1 antibody and mouse anti?human CD 34 antibody, as a blood vessel marker, was performed on frozen sections from macular and peripheral blocks of aged control donor eyes (n?=?12; mean age 78.8?years), and eyes with AMD (n?=?12; mean age 83.9?years). Pigment in retinal pigment epithelium (RPE) and choroidal melanocytes was bleached. Three independent observers scored the immunohistochemical reaction product. Results In the macular region, TSP?1 expression was observed intensely in Bruch's membrane and weakly in RPE basement membrane, choriocapillaris, and the wall of large choroidal blood vessels in the aged control eyes. In eyes with AMD, TSP?1 immunoreactivity was significantly lower in all structures except RPE basement membrane (p<0.01). There was significantly lower TSP?1 in the far periphery than the equator and submacular regions in all eyes. TSP?1 immunoreactivity was low in choroidal neovascularisation (CNV), but it was high and diffuse in adjacent scar tissue. Conclusion These findings suggest that decreased TSP?1 in Bruch's membrane and choroidal vessels during AMD may permit the formation of CNV.
Uno, K; Bhutto, I A; McLeod, D S; Merges, C; Lutty, G A
The invention relates to diagnostics and therapeutics and animal models for macular degeneration, specifically as they relate to the association described herein between macular degeneration and arterial wall disruptive disorders. In one embodiment, the invention provides kits and methods for diagnosing macular degeneration comprising identifying a marker for an arterial wall disruptive disorder, including an aneurysm. In one embodiment, the invention provides therapeutics for treating macular degeneration comprising delivering to a subject an agent useful for treating an arterial wall disruptive disorder, including an aneurysm.
Hageman; Gregory S. (Coralville, IA)
Among macular diseases, choroidal neovascularization (CNV) is one of the most common causes of visual loss, especially in the form associated with age-related macular degeneration and pathologic myopia. Research on these diseases has recently evaluated new treatment modalities that use laser light differently; among these, photodynamic therapy (PDT) has been introduced in the clinical practice, allowing us to expand the possibility of reducing visual loss in patients affected by CNV. With PDT, a photosensitizer (verteporfin, VisudyneTM) is injected intravenously, and it selectively binds to new vessels; low-power laser light exposure then activates the drug, leading to oxidative damage of the endothelium and new vessels thrombosis. Yet, other therapies, such as transpupillary termotherapy, or the use of photocoagulation to cause feeder-vessel occlusion, could proof effective, but they need further investigation.
Menchini, Ugo; Virgili, Gianni; Giansanti, Fabrizio; Giacomelli, Giovanni; Cappelli, Stefania
An active duty marine corps service member had bilateral full thickness macular holes induced following accidental Q-switched laser exposure from a hand held Neodymium range finder (ANGVS-5). The right eye had a large hole nasal to the fovea, while the left eye had a much smaller hole closer to the fovea centralis. Over the 18 months following the injury, the left eye demonstrated mild progressive degradation in visual function, but retained 20/20 final visual acuity. In contrast, the hole in the right eye increased in size, developed a localized retinal detachment with cystic changes in the fovea, and had atrophy of the retinal pigment epithelium. Within 6 months after injury, acuity declined to 20/100. Macular hole surgery was performed with a goal of sealing the edges of the hole in order to allow resolution of the localized detachment and cystic changes in the fovea. In spite of surgical techniques that are generally successful in the treatment of macular holes associated with other etiologies, the fundus findings remained unchanged and visual acuity declined to 20/400. To the best of our knowledge, this is the first case report of macular hole surgery for this condition.
Custis, Peter H.; Gagliano, Donald A.; Zwick, Harry; Schuschereba, Steven T.; Regillo, Carl D.
Purpose To evaluate the pattern of age-related macular degeneration in the new foveal location after macular translocation surgery with 360 degree peripheral retinectomy for neovascular age-related macular degeneration. Methods Clinical data, fundus photos, and fluorescein angiograms of patients in the Duke Macular Translocation Study were reviewed with 2-year follow-up data. Results With 56 patients completing follow-up, no patient developed de novo choroidal neovascularization (CNV), geographic atrophy, or drusen in the new subfoveal retinal pigment epithelium bed. By 2 years, 14 patients (25%) developed recurrent CNV and 13 of these 14 recurrences clearly arose from the old CNV bed. Of the 13 recurrences clearly arising from the old bed, 12 of them had recurrent CNV that involved the margin of the bed closest to the repositioned fovea. Smokers were 5.3 times (95% confidence interval: 1.2–24) more likely to develop recurrent CNV over 2 years. Despite treatment, median visual acuity for the 14 eyes with recurrent CNV was 20/200 compared with 20/80 in eyes without recurrence. Conclusions Findings in this study support the hypotheses that the development of CNV occurs via a signaling mechanism from the fovea.
BAER, CLAXTON A.; RICKMAN, CATHERINE BOWES; SRIVASTAVA, SUNIL; MALEK, GOLDIS; STINNETT, SANDRA; TOTH, CYNTHIA A.
Background\\/Aims: Senescent Ccl2–\\/– mice develop cardinal features of human age-related macular degeneration (AMD). Loss-of-function single-nucleotide polymorphisms within CX3CR1 are associated with AMD. Methods: We generated Ccl2–\\/–\\/Cx3cr1–\\/– [double-knockout (DKO)] mice and evaluated the eyes using fundoscopy routine histology, immunochemistry, biochemistry and proteomics. Results: At 6 weeks old, all DKO mice developed AMD-like retinal lesions such as abnormal retinal pigment epithelium cells,
Chi-Chao Chan; Robert J. Ross; Defen Shen; Xiaoyan Ding; Zigurts Majumdar; Christine M. Bojanowski; Min Zhou; Robert Bonner; Jingsheng Tuo
The authors report surgical outcomes of full-thickness macular hole repair in two patients with idiopathic macular telangiectasia in a non-comparative case series. Both patients underwent pars plana vitrectomy with indocyanine green-assisted internal limiting membrane peeling and injection of 16% C(3)F(8) gas. Patients were imaged with optical coherence tomography (OCT) before and after surgery. The first patient demonstrated macular hole closure on examination and OCT with visual improvement from 20/50 preoperatively to 20/30 after macular hole surgery and subsequent cataract surgery. The second patient's hole closed per OCT immediately after surgery but reopened 4 months later, and visual acuity remained 20/70. Macular hole surgery may be an effective treatment in patients with idiopathic macular telangiectasia and full-thickness macular holes and should be further investigated. PMID:21158375
Gregori, Ninel; Flynn, Harry W
Recent imaging studies have suggested that macular pigment is decreased centrally in macular telangiectasia type 2 (MT2). The uptake of xanthophyll pigment into the macula is thought to be facilitated by a xanthophyll-binding protein (XBP). The Pi isoform of glutathione S-transferase (GSTP1) represents one such XBP with high binding affinity. This case-control study aimed to determine whether two common single-nucleotide polymorphisms (SNPs) of GSTP1 were associated with MT2. DNA samples from 39 cases and 21 controls were collected. Two polymorphic sites of Ile105Val and Ala114Val in exons 5 and 6 respectively, of the GSTP1 gene were analysed. Comparison of alleles and genotypes between cases and controls indicated that there were no statistically significant differences for either the Ile105Val SNP (P=0.43) or the Ala114Val SNP (P=0.85), or for any combinations; however, the homozygous at-risk genotype (GG) of the Ile105Val SNP was present in 8% of cases but absent in controls. This study found no statistically significant association between two common GSTP1 SNPs and MT2; however, a trend towards a greater frequency of the GG genotype of the Ile105Val SNP in cases is of great interest. The biological plausibility of disturbed macular pigment uptake in MT2 makes GSTP1 an excellent candidate gene. Further investigation is warranted in future studies of MT2. PMID:20499266
Szental, Joshua A; Baird, Paul N; Richardson, Andrea J; Islam, F M Amirul; Scholl, Hendrik P N; Charbel Issa, Peter; Holz, Frank G; Gillies, Mark; Guymer, Robyn H
A bismuth oxychloride effect pigment has a zinc oxide or microfine titanium dioxide particulate at about the surface of the crystals of the bismuth oxychloride. The pigment is prepared by, for instance, growing the bismuth oxychloride crystals, and adding the particulate before the hydrolysis is complete.
Cao; Paul B. (Ossining, NY); Venturini; Michael (Yorktown Hts., NY)
Pigment abnormalities have been reported to occur on both sides of flatfish. Hypomelanosis or pseudo-albinism, characterized by white patches or areas devoid of normal pigmentation on the ocular surface of the skin, is common in both wild and hatchery reared flatfish. The blind side may display hypermelanosis in the form of dark spots, known as ambicoloration of the skin. The
Arietta Venizelos; Daniel D Benetti
PURPOSE: To report the ocular complications associated with the limited macular translocation procedure.METHODS: Retrospective review of 153 consecutive eyes of 151 patients that had the limited macular translocation procedure for subfoveal choroidal neovascularization between April 1996 and February 1999. The major study variables investigated included the incidence of specific ocular complications and their impact on visual acuity at 3 months
Gildo Y Fujii; Dante J Pieramici; Mark S Humayun; Andrew P Schachat; Sandra M Reynolds; Michele Melia; Eugene De Juan
BACKGROUND—Most idiopathic macular holes can be closed by a surgical procedure combining vitrectomy, posterior hyaloid ablation, and fluid-gas exchange followed by postoperative positioning. Reopening of closed macular holes has been reported, but its frequency is not known. Here the incidence of reopening after successful macular hole surgery is reported.?METHODS—77 consecutive cases of idiopathic macular holes operated with autologous platelet injection between July 1993 and October 1995 were reviewed. The procedure consisted of three port vitrectomy, posterior hyaloid removal, non-expansile fluid-gas exchange, and autologous platelet injection followed by face down positioning. The incidence of reopening was analysed in the cohort of the 72 anatomical successes.?RESULTS—Mean follow up was 12.3 months. The macular hole reopened in five eyes of five patients (five out of 72 patients, 6.9%), in four cases after cataract extraction. In four cases too, an epiretinal membrane was noted, either clinically or during reoperation, and fluorescein leakage in the macular area was present in two cases. Three of the five cases of reopening were reoperated and all three were anatomical successes.?CONCLUSION—Late macular hole reopening occurred in five out of 72 patient, and in four cases after cataract surgery. The presence of an epiretinal membrane around the hole in four of them suggested that tractional forces were responsible for the reopening. Reoperation, performed in three cases, again closed the macular holes.??
Paques, M.; Massin, P.; Santiago, P.; Spielmann, A.; Le Gargasson, J.-F.; Gaudric, A.
The aim of this paper is to review current knowledge relating to the monogenic macular dystrophies, with discussion of currently mapped genes, chromosomal loci and genotype-phenotype relationships. Inherited systemic disorders with a macular dystrophy component will not be discussed.
Michaelides, M; Hunt, D; Moore, A
This resource describes protocols and gives instructional information for carrying out an undergraduate laboratory exercise in vertebrate physiology. Students learn and analyze the dynamics of pigment granule transport in the chromatorphores of fishes. This exercise may be used as a stand alone exercise suitable for lower division undergraduate courses, or may be expanded as a scientific-inquiry based exercise for upper-level undergraduate courses. It includes student outlines, instructor's notes, and suggested questions for laboratory reports.
Kathryn B. Toner (;); Sally E. Nyquist (Bucknell University;)
Purpose: The purpose of this study was to evaluate the safety and efficacy of intravitreal triamcinolone acetonide injection in patients with diffuse diabetic macular edema. We also compared the effect of intravitreal triamcinolone with macular grid laser photocoagulation in macular edema. Patients and Methods: Thirty patients with diabetic diffuse macular edema unresponsive to grid laser photocoagulation for at least 4
The suitability of visible spectral response of vegetation for remote sensing has been investigated with field and laboratory studies on canopy and chloroplastidial pigments, respectively. To simulate band-spectral and hyperspectral sensing, measurements were taken both in wavebands and with fine resolution of wavelength. Vegetation species and maturity stages were distinguished with average reflectance and characteristic absorption features. The methodology was tried on both land vegetation, viz. jute canopy of West Bengal and marine plant, viz. green algae of the eastern coast of India. The absorbance variation within visible wavelength range was observed with both mixed chlorophyll solution and solutions of chromatographically separated pigments. The different characteristic absorption peaks were identified, which were quite different for higher plants and algae. The gradual changes in spectral response of leaf pigments with senescence in a common higher plant were systematically investigated with both original leaf extracts and artificial mixtures of fresh and decomposed chlorophyll solutions at different ratios. Mathematical models were put forward for both average and hyperspectral absorption features to track the experimental plots and estimate absorption at different wavelengths.
RayChaudhuri, Barun; Bhaumik, Subarnarekha
Background Oxidative damage to the retinal pigment epithelium might be involved in the pathogenesis of age related macular degeneration.\\u000a Thus antioxidative protection represents a rationale for a causative therapy or prophylaxis. The aim of the present study\\u000a is to evaluate antioxidative properties of vitamin C and pyruvate at retinal pigment epithelial (RPE) cells exposed to oxidative\\u000a stress.\\u000a \\u000a \\u000a \\u000a Methods The ability of vitamin
Oliver Zeitz; Lars Schlichting; Gisbert Richard; Olaf Strauß
Hydroxytyrosol (HTS) is a natural polyphenol abundant in olive oil. Increasing evidence indicates HTS has beneficial effect on human health for preventing various diseases. In the present study, we investigated the protective effects of HTS on acrolein-induced toxicity in human retinal pigment epithelial cell line, ARPE-19, a cellular model of smoking- and age-related macular degeneration. Acrolein, a major compo- nent
Zhongbo Liu; Lijuan Sun; Lu Zhu; Xu Jia; Xuesen Li; Haiqun Jia; Ying Wang; Peter Weber; Jiangang Long; Jiankang Liu
The highest incidences of cancer are found in the skin, but endogenous pigmentation is associated with markedly reduced risk. Agents that enhance skin pigmentation have the potential to reduce both photodamage and skin cancer incidence. The purpose of this review is to evaluate agents that have the potential to increase skin pigmentation. These include topically applied substances that simulate natural pigmentation: dihydroxyacetone and melanins; and substances that stimulate the natural pigmentation process: psoralens with UVA (PUVA), dimethylsulfoxide (DMSO), L-tyrosine, L-Dopa, lysosomotropic agents, diacylglycerols, thymidine dinucleotides, DNA fragments, melanocyte stimulating hormone (MSH) analogs, 3-isobutyl-1-methylxanthine (IBMX), nitric oxide donors, and bicyclic monoterpene (BMT) diols. These agents are compared with regards to efficacy when administered to melanoma cells, normal human epidermal melanocytes, animal skin, and human skin. In addition, mechanisms of action are reviewed since these may reveal issues related to both efficacy and safety. Both dihydroxyacetone and topically applied melanins are presently available to the consumer, and both of these have been shown to provide some photoprotection. Of the pigmentation stimulators, only PUVA and MSH analogs have been tested extensively on humans, but there are concerns about the safety and side effects of both. At least some of the remaining pigmentation stimulators under development have the potential to safely induce a photoprotective tan. PMID:11684462
Brown, D A
A 28-year-old healthy male complaining of vision loss in his right eye was discovered to have localized bi-nasal macular edema in the presence of a pituitary adenoma. The presence of a junctional scotoma composed by a central scotoma in the right eye associated with superior temporal quadrantanopia in the fellow eye was seen. The pattern detected in the visual field suggested the presence of an expansive mass at the level of the optic chiasm. Optical coherence tomography findings also revealed subtle macular thickness beyond normal in the superior and nasal quadrants of both maculae. This report illustrates the importance of suspecting a pituitary adenoma in the light of uncharacteristic retinal alterations.
Lavaque, Alejandro J; Yilmaz, Taygan; Cordero-Coma, Miguel
The retina exhibits an inherent autofluorescence that is imaged ophthalmoscopically as fundus autofluorescence. In clinical settings, fundus autofluorescence examination aids in the diagnosis and follow-up of many retinal disorders. Fundus autofluorescence originates from the complex mixture of bisretinoid fluorophores that are amassed by retinal pigment epithelial (RPE) cells as lipofuscin. Unlike the lipofuscin found in other cell-types, this material does not form as a result of oxidative stress. Rather, the formation is attributable to non-enzymatic reactions of vitamin A aldehyde in photoreceptor cells; transfer to RPE occurs upon phagocytosis of photoreceptor outer segments. These fluorescent pigments accumulate even in healthy photoreceptor cells and are generated as a consequence of the light capturing function of the cells. Nevertheless, the formation of this material is accelerated in some retinal disorders including recessive Stargardt disease and ELOVL-4-related retinal degeneration. As such, these bisretinoid side-products are implicated in the disease processes that threaten vision. In this article, we review our current understanding of the composition of RPE lipofuscin, the structural characteristics of the various bisretinoids, their related spectroscopic features and the biosynthetic pathways by which they form. We will revisit factors known to influence the extent of the accumulation and therapeutic strategies being used to limit bisretinoid formation. Given their origin from vitamin A aldehyde, an isomer of the visual pigment chromophore, it is not surprising that the bisretinoids of retina are light sensitive molecules. Accordingly, we will discuss recent findings that implicate the photodegradation of bisretinoid in the etiology of age-related macular degeneration.
Sparrow, Janet R.; Gregory-Roberts, Emily; Yamamoto, Kazunori; Blonska, Anna; Ghosh, Shanti Kaligotla; Ueda, Keiko; Zhou, Jilin
Purpose. The authors' previous studies showed that the Wnt signaling pathway is activated in the retinas and retinal pigment epithelia of animal models of age-related macular degeneration (AMD) and diabetic retinopathy (DR). The purpose of this study was to investigate the role of the canonical Wnt pathway in pathogenesis of these diseases. Methods. The Wnt pathway was activated using the Wnt3a-conditioned medium and adenovirus expressing a constitutively active mutant of ?-catenin (Ad-S37A) in ARPE19, a cell line derived from human RPE. Ad-S37A was injected into the vitreous of normal rats to activate the Wnt pathway in the retina. Accumulation of ?-catenin was determined by Western blot analysis, and its nuclear translocation was revealed by immunocytochemistry. Inflammatory factors were quantified by Western blot analysis and ELISA. Oxidative stress was determined by measuring intracellular reactive oxygen species (ROS) generation and nitrotyrosine levels. Results. The Wnt3a-conditioned medium and Ad-S37A both increased ?-catenin levels and its nuclear translocation in ARPE19 cells, suggesting activation of the canonical Wnt pathway. Activation of the Wnt pathway significantly upregulated the expression of VEGF, NF-?B, and TNF-?. Further, Ad-S37A induced ROS generation in a dose-dependent manner. Wnt3a also induced a twofold increase of ROS generation. Intravitreal injection of Ad-S37A upregulated the expression of VEGF, ICAM-1, NF-?B, and TNF-? and increased protein nitrotyrosine levels in the retinas of normal rats. Conclusions. Activation of the canonical Wnt pathway is sufficient to induce retinal inflammation and oxidative stress and plays a pathogenic role in AMD and DR.
Zhou, Ti; Hu, Yang; Chen, Ying; Zhou, Kevin K.; Zhang, Bin; Gao, Guoquan; Ma, Jian-xing
The aryl hydrocarbon receptor (AhR) is a nuclear receptor that regulates xenobiotic metabolism and detoxification. Herein, we report a previously undescribed role for the AhR signaling pathway as an essential defense mechanism in the pathogenesis of early dry age-related macular degeneration (AMD), the leading cause of vision loss in the elderly. We found that AhR activity and protein levels in human retinal pigment epithelial (RPE) cells, cells vulnerable in AMD, decrease with age. This finding is significant given that age is the most established risk factor for development of AMD. Moreover, AhR(-/-) mice exhibit decreased visual function and develop dry AMD-like pathology, including disrupted RPE cell tight junctions, accumulation of RPE cell lipofuscin, basal laminar and linear-like deposit material, Bruch's membrane thickening, and progressive RPE and choroidal atrophy. High-serum low-density lipoprotein levels were also observed in AhR(-/-) mice. In its oxidized form, this lipoprotein can stimulate increased secretion of extracellular matrix molecules commonly found in deposits from RPE cells, in an AhR-dependent manner. This study demonstrates the importance of cellular clearance via the AhR signaling pathway in dry AMD pathogenesis, implicating AhR as a potential target, and the mouse model as a useful platform for validating future therapies. PMID:24106308
Hu, Peng; Herrmann, Rolf; Bednar, Amanda; Saloupis, Peter; Dwyer, Mary A; Yang, Ping; Qi, Xiaoping; Thomas, Russell S; Jaffe, Glenn J; Boulton, Michael E; McDonnell, Donald P; Malek, Goldis
PURPOSE The retinal pigmented epithelium (RPE) expresses many genes that play important roles in the support and maintenance of photoreceptors. The present study was conducted to develop a system amenable to the dissection of the temporal function of these genes, specifically within RPE cells. Transgenic mice were generated and characterized in which the expression of Cre recombinase could be specifically induced within the RPE. METHODS Transgenic mice carrying the human vitelliform macular dystrophy-2 (VMD2) promoter (PVMD2)–directed reverse tetracycline-dependent transactivator (rtTA) and the tetracycline-responsive element (TRE)–directed cre were generated. Inducible Cre expression was achieved by feeding doxycycline to these mice and was characterized by using a Cre-activatable lacZ reporter mouse strain (R26R). RESULTS A ?-galactosidase assay of rtTA/Cre-R26R mice demonstrated that the basal level of Cre expression without doxycycline induction was negligible. Addition of doxycycline led to induction of RPE-specific Cre expression/function at least from embryonic day 9 to postnatal day 60. The highest induction occurred at approximately postnatal day 4. As measured by ERG and histology, retinal function and morphology were normal in 10-month-old rtTA/Cre mice that were treated with doxycycline at weaning age. CONCLUSIONS Transgenic mice were generated that express Cre recombinase in the RPE in an inducible fashion. These mice will be useful for studies of the RPE-specific role of genes that are expressed in the RPE as well as other cells, particularly for avoiding embryonic lethality and dissecting the function of genes that play dual roles in development and adulthood.
Le, Yun-Zheng; Zheng, Wei; Rao, Peng-Cheng; Zheng, Lixing; Anderson, Robert E.; Esumi, Noriko; Zack, Donald J.; Zhu, Meili
Purpose Our objective was to comprehensively assess the nature and chronology of neural remodeling in retinal degenerations triggered by light-induced retinal damage (LIRD) in adult albino rodents. Our primary hypothesis is that all complete photoreceptor degenerations devolve to extensive remodeling. An hypothesis emergent from data analysis is that the LIRD model closely mimics late-stage atrophic age relared macular degeneration (AMD). Methods Sprague-Dawley (SD) rats received intense light exposures of varied durations and survival times ranging from 0 to 240 days. Remodeling was visualized by computational molecular phenotyping (CMP) of a small molecule library: 4-aminobutyrate (?), arginine (R), aspartate (D), glutamate (E), glutamine (Q), glutathione (J), glycine (G), and taurine (?). This library was augmented by probes for key proteins such as rod opsin, cone opsin and cellular retinal binding protein (CRALBP). Quantitative CMP was used to profile 160 eyes from 86 animals in over 6,000 sections. Results The onset of remodeling in LIRD retinas is rapid, with immediate signs of metabolic stress in photoreceptors, the retinal pigmented epithelium (RPE), the choriocapillaris, and Müller cells. In particular, anomalous elevated aspartate levels appear to be an early stress marker in photoreceptors. After the stress phase, LIRD progresses to focal photoreceptor degeneration within 14 days and extensive remodeling by 60 days. RPE and choriocapillaris losses parallel Müller cell distal seal formation, with progressive neuronal migration, microneuroma evolution, fluid channel formation, and slow neuronal death. The remaining retina in advanced light damage can be classified as survivor, light damage (LD), or decimated zones where massive Müller cell and neuronal emigration into the choroid leaves a retina depleted of neurons and Müller cells. These zones and their transitions closely resemble human geographic atrophy. Across these zones, Müller cells manifest extreme changes in the definitive Müller cell ?QE signature, as well as CRALBP and arginine signals. Conclusions LIRD retinas manifest remodeling patterns of genetic retinal degeneration models, but involve no developmental complexities, and are ultimately more aggressive, devastating the remaining neural retina. The decimation of the neural retina via cell emigration through the perforated retina-choroid interface is a serious denouement. If focal remodeling in LIRD accurately profiles late stage atrophic age-related macular degenerations, it augurs poorly for simple molecular interventions. Indeed, the LIRD profile in the SD rat manifests more similarities to advanced human atrophic AMD than most genetically or immunologically induced murine models of AMD.
Jones, B.W.; Watt, C.B.; Vazquez-Chona, F.; Vaughan, D.K.; Organisciak, D.T.
PURPOSE: To report the incidence of macular changes following pars plana vitrectomy with peeling of the internal limiting membrane (ILM) for idiopathic macular hole.DESIGN: Prospective consecutive series.METHODS: In a prospective study 105 eyes of 105 patients underwent vitrectomy for idiopathic macular holes. Surgery consisted of a standard three-port vitrectomy, induction of a posterior hyaloid detachment, removal of epiretinal membranes including
Christos Haritoglou; Carolin A Gass; Markus Schaumberger; Oliver Ehrt; Arnd Gandorfer; Anselm Kampik
PurposeTo describe patients with full-thickness macular holes (FTMHs) and lamellar macular holes (LMHs) in association with type 2 idiopathic macular telangiectasia (type 2 IMT).MethodsSix patients with either FTMH or LMH and type 2 IMT were evaluated by means of optical coherence tomography (OCT) imaging, funduscopy, and fluorescein angiography.ResultsThe age of the examined patients ranged from 57 to 70 years (mean
P Charbel Issa; H P N Scholl; A Gaudric; P Massin; A E Kreiger; S Schwartz; F G Holz
The photosynthetically-active pigment protein complexes of procaryotes and eucaryotes include chlorophyll proteins, carotenochlorophyll proteins, and biliproteins. They are either integral components or attached to photosynthetic membranes. Detergents are frequently required to solubilize the pigment-protein complexes. The membrane localization and detergent solubilization strongly suggest that the pigment-protein complexes are bound to the membranes by hydrophobic interactions. Hydrophobic interactions of proteins are characterized by an increase in entropy. Their bonding energy is directly related to temperature and ionic strength. Hydrophobic-interaction chromatography, a relatively new separation procedure, can furnish an important method for the purification of pigment-protein complexes. Phycobilisome purification and properties provide an example of the need to maintain hydrophobic interactions to preserve structure and function.
Siegelman, H W
Purpose High-temperature requirement serine protease (HTRA1) was identified as a candidate age-related macular degeneration gene in multiple genetic studies in humans. To date, no functional studies have shown a mechanism for HTRA1 to instigate ocular tissue abnormalities. In the present study, the authors focused on a substrate of HTRA1, fibronectin, because fibronectin fragments (Fnfs) stimulate biochemical events in other age-related degenerative diseases that are analogous to changes associated with age-related macular degeneration (AMD). The purpose of the study was to determine whether Fnfs stimulate the release of proinflammatory and catabolic cytokines from murine retinal pigment epithelium (RPE). Methods Fibronectin was purified from murine serum by gelatin cross-linked agarose chromatography and subsequently was enzymatically digested with ?-chymotrypsin. The bioactivity of Fnfs was verified by measuring levels of IL-6 and TNF-? in Fnf-exposed murine splenocytes. To analyze the effect of Fnfs on RPE, cytokine and chemokine levels in RPE culture supernatants were assayed by ELISA. Results IL-6 and TNF-? proinflammatory cytokines were released from primary murine splenocytes in proportion to the dose and length of Fnf treatment, indicating that ?-chymotryptic digests of fibronectin are biologically active. Fnf treatment of murine RPE cells stimulated the release of microgram and nanogram levels of IL-6, MMP-3, MMP-9, and MCP-1, whereas only picogram levels were detected in untreated cells. Conclusions Fnfs stimulate the release of proinflammatory cytokines, matrix metalloproteinases, and monocyte chemoattractant protein from murine RPE cells. This observation indicated that Fnfs could contribute to ocular abnormalities by promoting inflammation, catabolism, and monocyte chemoattraction.
Austin, Bobbie Ann; Liu, Baoying; Li, Zhuqing; Nussenblatt, Robert B.
This fascinating online exhibit deals with the use of pigment and provides visitors with an "Overview", "History of Use", "Making the Pigment" and "Technical Details" for dozens of pigments that are "some of the most historically important in art". Visitors can click on "Choose a Pigment" to see a 3D image of such beauties as Cerulean Blue, Ultramarine, Naples Yellow, and Orpiment. Visitors can see a timeline of when these pigments were discovered, if they have continued being used, and in what form, artificial or natural. Carbon Black and Bone Black were the earliest pigments, and are still used today, and Titanium White is the most recent discovery, and it came into existence in 1921. The "Make Paintings" link is where visitors will probably have the most fun on the site, as they can see the progress of a painting in watercolor, pastels, oil, acrylic and the now little used method of egg tempera. Additionally, each technique is explained in detail, highlighted by photos that visitors can zoom in on for closer scrutiny.
Pigment epithelium-derived factor is well known as a secreted glycoprotein with multiple functions, such as anti-angiogenic, neuroprotective and anti-tumor activities. However, its intracellular role remains unknown. The present study was performed to demonstrate the intracellular function of pigment epithelium-derived factor on triglyceride degradation. Hepatic pigment epithelium-derived factor levels increased at the early stage and subsequently decreased after 16 weeks in high-fat-diet-fed mice compared to those in chow-fed mice. Similarly, oleic acid led to long-term downregulation of pigment epithelium-derived factor in HepG2 cells. Endogenous pigment epithelium-derived factor was an intracellular protein with cytoplasmic distribution in hepatocytes by immunostaining. Exogenous FITC-labeled pigment epithelium-derived factor could be absorbed into hepatocytes. Both signal peptide deletion and full-length pigment epithelium-derived factor transfection HeLa cells and hepatocytes promoted triglyceride degradation. Intracellular pigment epithelium-derived factor co-immunoprecipitated with adipose triglyceride lipase and promoted triglyceride degradation in an adipose triglyceride lipase-dependent manner. Additionally, pigment epithelium-derived factor bound to the C-terminal of adipose triglyceride lipase (aa268-504) and adipose triglyceride lipase-G0/G1 switch gene-2 complex simultaneously, which facilitated adipose triglyceride lipase-G0/G1 switch gene-2 translocation onto lipid droplet using bimolecular fluorescence complementation assay. Moreover, knockdown of endogenous pigment epithelium-derived factor in hepatocytes diminished triglyceride degradation. Taken together, these results indicate that hepatic pigment epithelium-derived factor was decreased in obese mice accompanied with hepatic steatosis. Intracellular pigment epithelium-derived factor binds to and facilitates adipose triglyceride lipase translocation onto lipid droplet, which promotes triglyceride degradation. These findings suggest that a decreased level of hepatic pigment epithelium-derived factor may contribute to hepatic steatosis in obesity. PMID:23886488
Dai, Zhiyu; Zhou, Ti; Li, Cen; Qi, Weiwei; Mao, Yuling; Lu, Juling; Yao, Yachao; Li, Lei; Zhang, Ting; Hong, Honghai; Li, Shuai; Cai, Weibin; Yang, Zhonghan; Ma, Jianxing; Yang, Xia; Gao, Guoquan
The rs1061170T/C variant encoding the Y402H change in complement factor H (CFH) has been identified by genome-wide association studies as being significantly associated with age-related macular degeneration (AMD). However, the precise mechanism by which this CFH variant impacts the risk of AMD remains largely unknown. Oxidative stress plays an important role in many aging diseases, including cardiovascular disease and AMD. A large amount of oxidized phospholipids (oxPLs) are generated in the eye because of sunlight exposure and high oxygen content. OxPLs bind to the retinal pigment epithelium and macrophages and strongly activate downstream inflammatory cascades. We hypothesize that CFH may impact the risk of AMD by modulating oxidative stress. Here we demonstrate that CFH binds to oxPLs. The CFH 402Y variant of the protective rs1061170 genotype binds oxPLs with a higher affinity and exhibits a stronger inhibitory effect on the binding of oxPLs to retinal pigment epithelium and macrophages. In addition, plasma from non-AMD subjects with the protective genotype has a lower level of systemic oxidative stress measured by oxPLs per apolipoprotein B (oxPLs/apoB). We also show that oxPL stimulation increases expression of genes involved in macrophage infiltration, inflammation, and neovascularization in the eye. OxPLs colocalize with CFH in drusen in the human AMD eye. Subretinal injection of oxPLs induces choroidal neovascularization in mice. In addition, we show that the CFH risk allele confers higher complement activation and cell lysis activity. Together, these findings suggest that CFH influences AMD risk by modulating oxidative stress, inflammation, and abnormal angiogenesis.
Shaw, Peter X.; Zhang, Li; Zhang, Ming; Du, Hongjun; Zhao, Ling; Lee, Clara; Grob, Seanna; Lim, Siok Lam; Hughes, Guy; Lee, Janet; Bedell, Matthew; Nelson, Mark H.; Lu, Fang; Krupa, Martin; Luo, Jing; Ouyang, Hong; Tu, Zhidan; Su, Zhiguang; Zhu, Jin; Wei, Xinran; Feng, Zishan; Duan, Yaou; Yang, Zhenglin; Ferreyra, Henry; Bartsch, Dirk-Uwe; Kozak, Igor; Zhang, Liangfang; Lin, Feng; Sun, Hui; Feng, Hong; Zhang, Kang
A method and composition for treating macular disorders. A pharmologically effective amount of a carbonic anhydrase inhibitor is combined with a pharmologically effective amount of an ocular hypotensive agent sufficient to improve visual function.
A 40-year-old man with decreasing visual acuity in his left eye over 1 year, diagnosed elsewhere as vein occlusion and treated unsuccessfully by systemic steroids was reported. Retrospective analysis of available previous imaging studies was undertaken, and a retrospective diagnosis of idiopathic macular telangiectasia (IMT) was made. Examination revealed subfoveal neovascularization and retinochoroidal anastomosis (RCA) in his left eye with macular edema and exudates surrounding it. The right eye was normal. Current fluorescein angiography (FA) confirmed the presence of choroidal neovascularization and RCA, and optical coherence tomography (OCT) demonstrated cystoid macular edema and subfoveal neovascularization.The patient was diagnosed with unilateral idiopathic macular telangiectasia complicated by subretinal neovascularization. The presences of a choroidal neovascularization process and an RCA have not, to our knowledge, been reported in this type of IMT. PMID:20337307
Mezad-Koursh, Daphna; Zayit-Soudry, Shiri; Barak, Adiel; Loewenstein, Anat
Home » Photos, Images, and Videos » Search Results Photos, Images, and Videos Search Results Instructions for Downloading Photographs and Images Description: A fundus photo showing intermediate age-related macular degeneration. Credit: National ...
Objective We evaluated monozygotic twin pairs with discordant age-related macular degeneration (AMD) phenotypes to assess differences in behavioral and nutritional factors. Design Case series. Participants Caucasian male twin pairs from the United States Twin Study of Macular Degeneration. Methods Twin pairs were genotyped to confirm monozygosity. Ocular characteristics were evaluated based on fundus photographs using the Wisconsin Grading System and a 5-grade Clinical Age-Related Maculopathy Staging System. We selected twin pairs discordant in each of the following phenotypic categories: Stage of AMD (n = 28), drusen area (n = 60), drusen size (n = 40), and increased pigment area (n = 56). The Wilcoxon signed-rank test and linear regression were used to assess associations between behavioral and nutritional characteristics and each phenotype within discordant twin pairs. Main Outcome Measures Differences in smoking and dietary factors within twin pairs discordant for stage of AMD, drusen area, drusen size, and pigment area. Results Representative fundus photographs depict the discordant phenotypes. Pack-years of smoking were higher for the twin with the more advanced stage of AMD (P = 0.05). Higher dietary intake of vitamin D was present in the twins with less severe AMD (P = 0.01) and smaller drusen size (P = 0.05) compared with co-twins, adjusted for smoking and age. Dietary intakes of betaine and methionine were significantly higher in the twin with lower stage of AMD (P = 0.009) and smaller drusen area (P = 0.03), respectively. Conclusions The twin with the more advanced stage of AMD, larger drusen area, drusen size, and pigment area tended to be the heavier smoker. The twin with the earlier stage of AMD, smaller drusen size and area, and less pigment tended to have higher dietary vitamin D, betaine, or methionine intake. Results suggest that behavioral and nutritional factors associated with epigenetic mechanisms are involved in the etiology of AMD, in addition to genetic susceptibility.
Seddon, Johanna M.; Reynolds, Robyn; Shah, Heeral R.; Rosner, Bernard
Purpose To find the gene(s) responsible for macular telangiectasia type 2 (MacTel) by a candidate-gene screening approach. Methods Candidate genes were selected based on the following criteria: those known to cause or be associated with diseases with phenotypes similar to MacTel, genes with known function in the retinal vasculature or macular pigment transport, genes that emerged from expression microarray data from mouse models designed to mimic MacTel phenotype characteristics, and genes expressed in the retina that are also related to diabetes or hypertension, which have increased prevalence in MacTel patients. Probands from eight families with at least two affected individuals were screened by direct sequencing of 27 candidate genes. Identified nonsynonymous variants were analyzed to determine whether they co-segregate with the disease in families. Allele frequencies were determined by TaqMan analysis of the large MacTel and control cohorts. Results We identified 23 nonsynonymous variants in 27 candidate genes in at least one proband. Of these, eight were known single nucleotide polymorphisms (SNPs) with allele frequencies of >0.05; these variants were excluded from further analyses. Three previously unidentified missense variants, three missense variants with reported disease association, and five rare variants were analyzed for segregation and/or allele frequencies. No variant fulfilled the criteria of being causal for MacTel. A missense mutation, p.Pro33Ser in frizzled homolog (Drosophila) 4 (FZD4), previously suggested as a disease-causing variant in familial exudative vitreoretinopathy, was determined to be a rare benign polymorphism. Conclusions We have ruled out the exons and flanking intronic regions in 27 candidate genes as harboring causal mutations for MacTel.
Parmalee, Nancy L.; Schubert, Carl; Merriam, Joanna E.; Allikmets, Kaija; Bird, Alan C.; Gillies, Mark C.; Peto, Tunde; Figueroa, Maria; Friedlander, Martin; Fruttiger, Marcus; Greenwood, John; Moss, Stephen E.; Smith, Lois E.H.; Toomes, Carmel; Inglehearn, Chris F.
Aim To evaluate the distribution of fundus autofluorescence in patients with age?related macular degeneration and choroidal neovascularisation (CNV). Methods Colour fundus photographs, fundus fluorescein angiograms (FFA) and fundus autofluorescence images were obtained from a group of 40 patients (43 eyes) with age?related macular degeneration and purely classic or occult CNV. Only patients with newly diagnosed CNV and in whom autofluorescence images were obtained within 2?weeks from FFA were included. The distribution of autofluorescence was qualitatively evaluated, and the findings compared with those from colour fundus photographs and FFA. Results 29 (67%) eyes had classic CNV and 14 (33%) had occult CNV. In 26 (90%) eyes with classic CNV, a low autofluorescence signal was detected at the site of the CNV; in 7 (50%) eyes with occult CNV, multiple foci of low autofluorescence signal were detected. Outside the area affected by the lesion, homogeneous autofluorescence was observed in most of the cases (n?=?33, 77%). Similarly, homogeneous autofluorescence was commonly observed in fellow eyes (62%). A pattern of focal increased autofluorescence was rarely seen in eyes with CNV (n?=?4, 9%) or in fellow eyes (n?=?4, 15%). In 11 of 43 (25%) eyes, areas of increased autofluorescence, other than a pattern of focal increased autofluorescence, were detected. In four patients, autofluorescence images had been obtained before the development of CNV; in none was any increased autofluorescence detected before the formation of CNV. Conclusions Distinct patterns of autofluorescence were observed in eyes with pure classic and occult CNV. Increased autofluorescence was rarely seen in eyes with CNV and in fellow eyes, suggesting that increased autofluorescence, and thus, retinal pigment epithelium lipofuscin, may not play an essential part in the formation of CNV.
McBain, Vikki A; Townend, John; Lois, Noemi
Ophthalmic fundus imaging plays an important role in the advances in the pathophysiology of retinal diseases. Using fundus imaging, we studied morphological changes in the choroid, subretinal pathophysiology and photoreceptor and retinal pigment epithelial (RPE) cell damage, and functional abnormalities of photoreceptor cells in macular diseases. To evaluate the choroidal changes, we performed enhanced depth imaging optical coherence tomography (EDI-OCT) for macular diseases. Choroidal thickness both in the affected eyes and in the fellow eyes with choroidal vascular hyperpermeability was thicker in patients with central serous chorioretinopathy (CSC). Photodynamic therapy (PDT) reduced the hyperpermeability and led to choroidal thinning in eyes with CSC, whereas laser photocoagulation did not result in any change in choroidal thickness, suggesting different mechanism of action for these two forms of treatment. PDT also decreased choroidal thickness in eyes with polypoidal choroidal vasculopathy. These findings will help to elucidate the pathophysiologic features of CSC as well as responses to treatment. Patients with acute Vogt-Koyanagi-Harada (VKH) disease have markedly thickened choroids. Both the choroidal thickness and the retinal detachment in these patients decreased quickly with corticosteroid treatment. EDI-OCT can be used to evaluate the choroidal involvement in VKH disease in acute stages and may prove useful in the diagnosis and management of this disease. Dome-shaped macula is the result of a localized thickening of the sclera under the macula in highly myopic patients, and it cannot be categorized into any known type of staphyloma. EDI-OCT is helpful in monitoring the proposed site of pathophysiologic changes in the choroid and the sclera, and provides noninvasively information not available by other means. To clarify the subretinal changes and the mechanism of cell damage in macular detachment, we studied the clinical characteristics of yellow deposits (multiple dot-like yellow precipitates and subretinal yellow material) seen in CSC using fundus autofluorescence and OCT. The yellow deposits had highly reflective tissue in the intraretinal and subretinal spaces seen on OCT and hyperfluorescence on short-wave autofluorescence (SW-AF) examinations during the follow-up period. These findings may indicate that formations of yellow deposits are associated with the accumulation of the photoreceptor outer segments and metabolism and phagocytosis by macrophages or RPE cells. SW-AF also demonstrated a hypofluorescence corresponding to the accumulated areas of yellow deposits during the long term followup period. Another study using infrared autofluorescence examination demonstrated that the yellow deposits induced a decrease in melanin and the functional decline of RPE cells in CSC. These may indicate that the existence of depositions in eyes with CSC is associated with photoreceptor and RPE cells damage. Similar yellow deposits can also be seen in eyes with macular detachment, e. g. branch retinal vein occlusion. We report a new method of retinal densitometry using SW-AF examination by scanning laser ophthalmoscope. We named the technique autofluorescence densitometry (AFD). This technique can evaluate photopigment density from serial SW-AF images during exposure to excitation light. This new technique can examine a much broader macular area and create a distribution map of optical density of the photopigments. It is also easy to compare the distribution of the photopigment densities with other retinal imaging devices such as OCT. To investigate functional abnormalities in eyes with CSC, we measured the optical density of the photopigments using AFD in both the acute and quiescent phase. The photopigment density decreased at the serous retinal detachment. The density remained decreased immediately after resolution and showed delayed recovery. The photopigments decreased even in eyes with a morphologic recovery of the outer retina. AFD could identify the functional impairment of the outer retina as characterized by
Fuzzy logic and linguistic variables are used for the automatic interpretation of Raman spectra obtained from pigments found in cultural heritage art objects. Featured bands are extracted from a Raman spectrum of a reference pigment and the methodology for constructing the library is illustrated. An unknown spectrum is then interpreted automatically and a process for identifying the corresponding pigment is described. A reference library consisting of 32 pigments was built and the effectiveness of the algorithm was tested by the Raman spectroscopic analysis of 10 pigments that are known to have been extensively used in Byzantine hagiography. Binary mixtures of these pigments were also tested. The algorithm's level of identification was good even though extra peaks, noise, and background signals were encountered in the spectra. PMID:15282052
Ramos, Pablo Manuel; Ferré, Joan; Ruisánchez, Itziar; Andrikopoulos, Konstantinos S
The constituents of cottonseed pigment glands were fractionated by the use of column chromatography with DEAE cellulose ion\\u000a exchanger and silicic acid, and a new green pigment was isolated. The acute oral toxicity of the new pigment was determined\\u000a using rats as experimental animals. The LD-50 value obtained was 0.66 g\\/kg of body weight indicating that the new pigment\\u000a which
C. M. Lyman; A. S. El-Nockrashy; J. W. Dollahite
Pigments are important contributors to the appearance and healthful properties of both avocado fruits and the oils extracted from these fruits. This study determined carotenoid and chlorophyll pigment concentrations in the skin and three sections of the flesh (outer dark green, middle pale green, and inner yellow flesh-nearest the seed) and anthocyanin concentrations in the skin of Hass avocado during ripening at 20 degrees C. Pigments were extracted from frozen tissue with acetone and measured using high-performance liquid chromatography. Pigments were also measured in the oil extracted from freeze-dried tissue sections by an accelerated solvent extraction system using hexane. Carotenoids and chlorophylls identified in the skin, flesh, and oil were lutein, alpha-carotene, beta-carotene, neoxanthin, violaxanthin, zeaxanthin, antheraxanthin, chlorophylls a and b, and pheophytins a and b with the highest concentrations of all pigments in the skin. Chlorophyllides a and b were identified in the skin and flesh tissues only. As the fruit ripened and softened, the skin changed from green to purple/black, corresponding to changes in skin hue angle, and a concomitant increase in cyanidin 3-O-glucoside and the loss of chlorophyllide a. In flesh tissue, chroma and lightness values decreased with ripening, with no changes in hue angle. The levels of carotenoids and chlorophylls did not change significantly during ripening. As fruit ripened, the total chlorophyll level in the oil from the flesh sections remained constant but declined in the oil extracted from the skin. PMID:17177553
Ashton, Ofelia B O; Wong, Marie; McGhie, Tony K; Vather, Rosheila; Wang, Yan; Requejo-Jackman, Cecilia; Ramankutty, Padmaja; Woolf, Allan B
The Macular Photocoagulation Study (MPS) is a set of randomized, controlled clinical trials designed to evaluate the effectiveness of laser photocoagulation of neovascular lesions, secondary to age-related (senile) macular degeneration (AMD or SMD), ocula...
|The method for extracting and separating hydrophobic photosynthetic pigments proposed by Katayama "et al." ("Japanese Journal of Phycology," 42, 71-77, 1994) has been improved to introduce it to student laboratories at the senior high school level. Silica gel powder was used for removing water from fresh materials prior to extracting pigments by…
Katayama, Nobuyasu; Kanaizuka, Yasuhiro; Sudarmi, Rini; Yokohama, Yasutsugu
The method for extracting and separating hydrophobic photosynthetic pigments proposed by Katayama et al. (Japanese Journal of Phycology, 42, 71-77, 1994) has been improved to introduce it to student laboratories at the senior high school level. Silica gel powder was used for removing water from fresh materials prior to extracting pigments by a mixture of organic solvents that was also
Nobuyasu Katayama; Yasuhiro Kanaizuka; Yasutsugu Yokohama
Oxidative stress in the retinal pigment epithelium (RPE) is hypothesized to be a major contributor to the development of age-related macular degeneration (AMD). Mitochondrial manganese superoxide dismutase (MnSOD) is a critical antioxidant protein that scavenges the highly reactive superoxide radical. We speculated that specific reduction of MnSOD in the RPE will increase the level of reactive oxygen species in the retina/RPE/choroid complex leading to pathogenesis similar to geographic atrophy. To test this hypothesis, an Sod2-specific hammerhead ribozyme (Rz), delivered by AAV2/1 and driven by the human VMD2 promoter was injected subretinally into C57BL/6J mice. Dark-adapted full field electroretinogram (ERG) detected a decrease in the response to light. We investigated the age-dependent phenotypic and morphological changes of the outer retina digital fundus imaging and SD-OCT measurement of ONL thickness. Fundus microscopy revealed pigmentary abnormalities in the retina and these corresponded to sub-retinal and sub-RPE deposits seen in SD-OCT B-scans. Light and electron microscopy documented the localization of apical deposits and thickening of the RPE. In RPE flat-mounts we observed abnormally displaced nuclei and regions of apparent fibrosis in the central retina of the oldest mice. This region was surrounded by enlarged and irregular RPE cells that have been observed in eyes donated by AMD patients and in other mouse models of AMD.
Seo, Soo-jung; Krebs, Mark P.; Mao, Haoyu; Jones, Kyle; Conners, Mandy; Lewin, Alfred S.
Purpose. The retinal pigment epithelium (RPE) separates photoreceptors from choroidal capillaries, but in age-related macular degeneration (AMD) capillaries breach the RPE barrier. Little is known about human RPE tight junctions or the effects of serum on the retinal side of the RPE. Methods. Cultured human fetal RPE (hfRPE) was assessed by the transepithelial electrical resistance (TER) and the transepithelial diffusion of methylated polyethylene glycol (mPEG). Claudins and occludin were monitored by quantitative RT-PCR, immunoblotting, and immunofluorescence. Results. Similar to freshly isolated hfRPE, claudin-19 mRNA was 25 times more abundant than claudin-3. Other detectable claudin mRNAs were found in even lesser amounts, as little as 3000 times less abundant than claudin-19. Claudin-1 and claudin-10b were detected only in subpopulations of cells, whereas others were undetectable. Knockdown of claudin-19 by small interfering RNA (siRNA) eliminated the TER. siRNAs for other claudins had minimal effects. Serum affected tight junctions only when presented to the retinal side of the RPE. The TER increased 2 times, and the conductance of K+ relative to Na+ decreased without affecting the permeability of mPEG. These effects correlated with increased steady-state levels of occludin. Conclusions. Fetal human RPE is a claudin-19–dominant epithelium that has regional variations in claudin-expression. Apical serum decreases RPE permeability, which might be a defense mechanism that would retard the spread of edema due to AMD.
Peng, Shaomin; Rao, Veena S.; Adelman, Ron A.
Approximately one of every 10 women has a pigmented vulvar lesion. Given the risk of melanomas and pigmented vulvar intraepithelial neoplasia (squamous cell carcinoma in situ), proper evaluation of vulvar pigmented lesions is critical. Most vulvar lesions are benign; however, vulvar lesions grossly, dermoscopically, and histologically can appear atypical compared with pigmented lesions on the rest of the body. Thus, it is imperative to use not only a keen eye but also a low threshold for biopsy. PMID:20883921
The eggs of the brine shrimp, Artemia salina, vary in colour from pale cream to dark brown. This variation is due to different amounts of haematin in the egg shells. Nauplii of Artemia are bright orange in colour owing to a carotenoid pigment, esterified astaxanthin. The same carotenoid is present in the eggs. Adult Artemia which has been reared on
Barbara M. Gilchrist; J. Green
A 80-year-old male presented with a long time history of a localized red-brown macule with superficial lichenification and slight scaling in the right groin. An earlier skin biopsy revealed the presence of amyloid deposits. The patient therefore had a complete internal checkup including a rectal biopsy for exclusion of systemic amyloidosis. However, the laboratory data did not reveal any specific abnormalities including immunoglobulins and Bence-Jones protein. The rectal biopsy was also nonspecific. After skin examination, a rebiopsy was performed at our department showing acanthosis and spongiosis of the epidermis with parakeratosis. A homogenous eosinophilic deposit was present in the upper dermis and stained positive with thioflavine. At the second visit the patient wore a truss for a right inguinal hernia, perfectly matching the area of the skin lesion. Thus, the diagnosis of a localized macular amyloidosis was confirmed very likely due to permanent local friction. The classification of localized cutaneous amyloidoses should include local trauma as a cause to avoid unnecessary and exhausting internal checkups to exclude systemic involvement. PMID:11715396
Abels, C; Karrer, S; Landthaler, M; Szeimies, R M
The effect of betacyanin pigments from Amaranthus tricolor on the functional properties and colour of wheat flour in relation to the quality of Asian salted noodles was studied. Addition of Amaranthus pigments significantly decreased the viscosity of wheat flour pastes as well as hardness and adhesiveness of the gels. Low levels of Amaranthus pigments (0.1% and 0.5%) imparted a more
Fan Zhu; Yi-Zhong Cai; Harold Corke
Optical coherence tomography (OCT) has enabled objective measurement of the total retinal thickness in diabetic macular edema (DME). The central retinal thickness is correlated modestly with visual impairment and changes paradoxically after treatments compared to the visual acuity. This suggests the clinical relevance of the central retinal thickness in DME and the presence of other factors that affect visual disturbance. Recent advances in spectral-domain (SD) OCT have provided better delineation of the structural changes and fine lesions in the individual retinal layers. Cystoid spaces in the inner nuclear layer and outer plexiform layer are related to quantitative and qualitative parameters in fluorescein angiography. OCT often shows vitreoretinal interface abnormalities in eyes with sponge-like retinal swelling. Serous retinal detachment is sometimes accompanied by hyperreflective foci in the subretinal fluid, which exacerbates the pathogenesis at the interface of the photoreceptors and retinal pigment epithelium. Photoreceptor damage at the fovea is thought to be represented by disruption of the external limiting membrane or the junction between the inner and outer segment lines and is correlated with visual impairment. Hyperreflective foci in the outer retinal layers on SD-OCT images, another marker of visual disturbance, are associated with foveal photoreceptor damage.
The authors report the clinical findings of a civilian patient who unintentionally looked into the laser beam of a British range finder, obtained on the black market. The patient was investigated by fluorescein angiography. Indocyanine green angiography (ICG) and microperimetry both in the acute stage (2 hours) and four weeks later. Hundred mg prednisone tapered over 9 days was prescribed. Additionally 50 (mu) g tissue plasminogen activator (TPA) and 0.5 ml pure C2F6 were injected in the vitreous. In the acute phase hemorrhage was located beneath the retina, primarily beneath the retinal pigment epithelium. Retinal defects as seen initially over the subretinal blood, were reduced after four weeks, but a retinal defect ranging from the lasered site towards the fovea remained. Visual acuity slightly increased from 20/100 to 20/63. ICG showed a large hypofluorescent spot in the macula. The technical parameters of the range finder were: Nd:YAG laser (1064 nm), pulse duration 10 ns, beam divergence 1.5 mrad, energy 10 mJ. A range finder can produce severe macular injury. The primary laser tissue interaction mechanism seems to be explosive disruption of choroidal tissue. Intravitral injection of TPA and C2F6 may be an adjunct in the therapy of acute laser lesions. A late complication can be secondary choroidal neovascularization.
Roider, Johann; Buesgen, Patrick; Hoerauf, Hans; Laqua, Horst; Birngruber, Reginald
Purpose To investigate the development of polypoidal lesions using indocyanine green angiography (IA) in eyes with typical age-related macular degeneration (AMD). Methods We retrospectively reviewed the medical records of 47 consecutive patients (47 eyes) with typical AMD who had been followed up with IA for at least 2 years. Results At the initial visit, although all eyes showed classic and/or occult choroidal neovascularization (CNV) associated with AMD, no eyes showed polypoidal lesions by IA. However, during follow-up, 13 (27.7%) of the 47 eyes did show polypoidal lesions. All polypoidal lesions developed at the edge of persistent CNV or, more often, at the terminus of recently progressed CNV. Of 12 eyes with a final lesion area >8 disc area, 7 (58.3%) showed newly developed polypoidal lesions. In the eyes with these newly developed polypoidal lesions, the mean area of the vascular lesion had extended significantly from 10.50±7.88?mm2 to 20.87±10.21?mm2 during follow-up (P=0.0018). Conclusion The current observation suggests that IA of active AMD sometimes reveals polypoidal lesions if there is progression of the CNV in the subretinal pigment epithelium space.
Tsujikawa, A; Ojima, Y; Yamashiro, K; Ooto, S; Tamura, H; Nakata, I; Yoshimura, N
The presence of melanin pigment and/or melanocytes in pilomatricoma has been rarely documented. In this study, we analyzed the incidence and clinicopathological features of pigmented pilomatricoma. Fifty-seven consecutive pilomatricoma cases from 53 Japanese patients were examined in this study. In fourteen cases (24.6%), pigmentation was observed in pilomatricoma. This variant equally affected in males and females, and the common locations were the upper arm and face. Proliferation of dendritic melanocytes was observed within basaloid cell nests in all cases, and melanin pigment was also present within the cytoplasm of the basaloid cells in 11 cases. Melanin pigment was also present in the shadow cells in 7 cases. The incidence of pigmented pilomatricoma as documented in previous reports is approximately 10%. However, our analysis revealed that pigmented pilomatricoma was found in 24.6% of Japanese cases of pilomatricoma, thus, this variant is not uncommon and may be under-recognized. PMID:24040455
Ishida, Mitsuaki; Okabe, Hidetoshi
The presence of melanin pigment and/or melanocytes in pilomatricoma has been rarely documented. In this study, we analyzed the incidence and clinicopathological features of pigmented pilomatricoma. Fifty-seven consecutive pilomatricoma cases from 53 Japanese patients were examined in this study. In fourteen cases (24.6%), pigmentation was observed in pilomatricoma. This variant equally affected in males and females, and the common locations were the upper arm and face. Proliferation of dendritic melanocytes was observed within basaloid cell nests in all cases, and melanin pigment was also present within the cytoplasm of the basaloid cells in 11 cases. Melanin pigment was also present in the shadow cells in 7 cases. The incidence of pigmented pilomatricoma as documented in previous reports is approximately 10%. However, our analysis revealed that pigmented pilomatricoma was found in 24.6% of Japanese cases of pilomatricoma, thus, this variant is not uncommon and may be under-recognized.
Ishida, Mitsuaki; Okabe, Hidetoshi
We report a new mechanism of ocular trauma. A basketball was intentionally overinflated until it exploded, resulting in corneal edema, hyphema, iritis, vitreous hemorrhage, commotio retinae, and a macular hole. The macular hole did not close after observation and subsequent pars plana vitrectomy with posterior hyaloid removal, but a repeat vitrectomy with internal limiting membrane peeling resulted in hole closure. Basketball overinflation to the point of explosion is a potentially blinding practice of which the public and manufacturers should be made aware. PMID:23676239
Yonekawa, Yoshihiro; Miller, John B; Turalba, Angela V; Eliott, Dean
Macular amyloidosis is a form of cutaneous amyloidosis characterized by dusky-brown lesions usually located on the upper back between the shoulder blades. This report describes the case of a 45 year-old female presenting with hyperpigmented macules and lace-like, non-pruritic erythema in the sacral and cervical region as well as on both arms and legs. Histology revealed amyloid deposits in the papillary dermis which exhibited apple-green birefringence after Congo red staining. There were no systemic findings. This is a case of macular amyloidosis with an unusual presentation. The literature on the subject is also reviewed. PMID:22068763
Melo, Bárbara Lima Araújo; Costa, Igor Santos; Goes, Clara de Assis Martins; Tigre, Celina Aguiar Frota; André, Nara Frota
Diabetic macular edema (DME) is a leading cause of vision loss in older Americans. Thermal laser treatment remains the mainstay of treatment for DME. Recently, alternative primary treatments for DME have been evaluated. These treatments include intravitreal injections of steroids as well as pharmaceuticals containing antibodies against vascular endothelial growth factor (VEGF). Surgical treatment has been shown to be appropriate in selected cases. We review the evidence and scientific rationale for various primary treatment options in patients with DME. Regular and timely ophthalmologic evaluation remains crucial to recognition and treatment of macular edema in diabetic patients.
Ranchod, Tushar M; Fine, Stuart L
Pigments such as melanin, scytonemin and carotenoids protect microbial cells against the harmful effects of ultraviolet (UV) radiation. The role in UV protection has never been assigned to the prodigiosin pigment. In this work, we demonstrate that prodigiosin provides a significant level of protection against UV stress in Vibrio sp. DSM 14379. In the absence of pigment production, Vibrio sp. was significantly more susceptible to UV stress, and there was no difference in UV survival between the wild-type strain and non-pigmented mutant. The pigment's protective role was more important at higher doses of UV irradiation and correlated with pigment concentration in the cell. Pigmented cells survived high UV exposure (324 J/m(2)) around 1,000-fold more successfully compared to the non-pigmented mutant cells. Resistance to UV stress was conferred to the non-pigmented mutant by addition of exogenous pigment extract to the growth medium. A level of UV protection equivalent to that exhibited by the wild-type strain was attained by the non-pigmented mutant once the prodigiosin concentration had reached comparable levels to those found in the wild-type strain. In co-culture experiments, prodigiosin acted as a UV screen, protecting both the wild-type and non-pigmented mutants. Our results suggest a new ecophysiological role for prodigiosin. PMID:21547449
Bori?, Maja; Danev?i?, Tjaša; Stopar, David
1. Blepharisma undulans, a protozoan with a reddish pigment, shows increased oxygen consumption under the influence of light. 2. If the light intensity is high, the animals are killed during a burst of oxygen consumption. 3. If the blepharismas are first bleached by exposure to light of low intensity they show only slightly increased oxygen consumption under the influence of light and they are not killed. 4. A preparation in which the animals are killed by heat still shows the increase in oxygen consumption on illumination with brilliant light. The supernatant solution does so as well, as does an alcohol extract of the dye. 5. The conclusion is drawn that the blepharismas are killed during photooxidation of the pigment, but the mechanism of action is not clear. Several possibilities are considered in the discussion.
Giese, Arthur C.; Zeuthen, Erik
Best`s macular dystrophy, also known as vitelliform macular degeneration, is an autosomal dominant, early onset form of macular degeneration. The disease is characterized by a roughly circular deposit of lipofuscin beneath the pigment epithelium of the retinal macula. Linkage studies were performed in two families, one Irish and one German, segregating typical Best`s macular dystrophy. In the Irish family (BTMD1), linkage analysis mapped the disease causing gene to chromosome 11q13, in a 10 cM region between the microsatellite markers PYGM and D11S871. Both markers showed different recombinants with the disease phenotype. This is a region that has previously shown linkage in families affected with Best`s macular dystrophy. Lod scores of 9.63, 9.12, 6.92, and 6.83 at zero recombination, were obtained with markers D11S1344, D11S1361, D11S1357 and D11S903, respectively. This data places the disease locus definitvely within the region between PYGM and D11S871. Linkage has been significantly excluded in this region in the German family (FamE), thereby providing evidence for genetic heterogeneity in this disease. The retinal specific gene, rod outer membrane protein 1 (ROM1), which maps to this region, has been screened for mutations in family BTMD1 by SSCPE analysis and by direct sequencing. Some of the promoter region, the three exons, and both introns have been sequenced; however, no mutations were found. It is likely that a gene other than ROM1 within this region may be responsible for causing the disease phenotype.
Mansergh, F.C.; Kenna, P.F.; Farrar, G.J. [Trinity College, Dublin (United Kingdom)] [and others
In this fun, hands-on autumn activity, learners experiment to discover whether the colored substances in leaves can be separated from the leaves. Learners crush leaves and other natural materials and soak them in different liquids. They then carry out the technique of chromatography to separate out the pigments for observation. The activity is broken into three parts and includes follow-up and background information.
Education Development Center, Inc.
Purpose To report a case who had recurrence of macular hole retinal detachment (MHRD) after intravitreal ranibizumab injection (IVR) for the treatment of choroidal neovascularization (CNV) that arose from the damaged retinal pigment epithelium of the remaining macular hole (MH) edge, which had been successfully treated by pars plana vitrectomy (PPV) 15 years previously. Case Report A 67-year-old man with previous PPV for MHRD secondary to high myopia in the right eye had been under observation for 15 years after surgery. The retina had been successfully attached, but the MH remained open. He had CNV which arose from the remaining MH edge. IVR was performed for the treatment of CNV. One month after the injection, CNV was contracted but recurrence of MHRD occurred. PPV with an additional internal limiting membrane peeling, removal of the CNV membrane and 20% SF6 gas tamponade was performed. One year after the last surgery, his right retina was attached and the MH was closed successfully. Conclusion We propose that patients who undergo IVR should be carefully maintained and followed up for possible complications including the recurrence of MHRD.
Otsuka, Keiko; Imai, Hisanori; Shimoyama, Tsuyoshi; Nagai, Takayuki; Honda, Shigeru; Azumi, Atsushi
The stability of anthocyanin pigment extracts and food products containing anthocyanin extracts is enhanced by removal from the anthocyanin pigment extracts of nutrients which support yeast growth, constituents which react to produce off-flavor, and constituents which catalyze oxidation. These undesirable materials contained in anthocyanin extracts are removed by subjecting the extracts to ultrafiltration or dialysis to remove low molecular weight components from the extracts. The extracts are also subjected to ion exchange to remove additional of these undesirable constituents. Sufficient of these undesirable constituents can be removed from anthocyanin extracts so that, e.g., carbonated beverages containing the extracts may not support sufficient growth of yeasts to cause the beverages to become hazy and/or have an off-flavor, and so that when the extracts are used to prepare dry beverage powder mixtures after prolonged shelf storage, the mixtures may not obtain an off-flavor. Moreover, the oxidative stability and photostability of the anthocyanin pigment extracts may be enhanced by the process of this invention. Such processed anthocyanin extracts may have higher tinctoral powers, e.g., more brilliant red colors, and are less hygroscopic, and thus they may be suitable for coloring various solid food products including liquid and powder concentrates.
Hilton; Barney W. (Dallas, TX); Lin; Robert I. (Irving, TX); Topor; Michael G. (Farmer's Branch, TX)
PURPOSE: To conduct a prospective study of macular translocation in patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration.METHODS: In 10 eyes of 10 patients with subfoveal choroidal neovascularization and best-corrected visual acuity ranging from 20\\/50 to 20\\/800 (median, 20\\/111), the fovea was relocated by means of scleral imbrication, intentional retinal detachment with small posterior retinotomies, and partial fluid-air
Hilel Lewis; Peter K Kaiser; Sharon Lewis; Marc Estafanous
Age-related Macular Degeneration (AMD) is the leading cause of blindness among the elderly. While excellent treatment has emerged for neovascular disease, treatment for early AMD is lacking due to an incomplete understanding of the early molecular events. Cigarette smoking is the strongest epidemiologic risk factor, yet we do not understand how smoking contributes to AMD. Smoking related oxidative damage during the early phases of AMD may play an important role. This review explores how cigarette smoking and oxidative stress to the retinal pigmented epithelium (RPE) might contribute to AMD, and how the transcription factor Nrf2 can activate a cytoprotective response.
Cano, Marisol; Thimmalappula, Rajesh; Fujihara, Masashi; Nagai, Norihiro; Sporn, Michael; Wang, Ai Ling; Neufeld, Arthur H.; Biswal, Shyam; Handa, James T.
Age-related macular degeneration is one of the most serious diseases in elderly people because of its disasterous visual outcome and its prevalence. Even if the submacular and choroidal neovascular membranes could be surgically excised, severe damage or evacuation of retinal pigment epithelium is inevitable in the operated area. Pigmentary dystrophy is also a devastating hereditary eye disease with severe visual disturbance. Up to now, there have been no effective treatments for either of them. We conducted basic experiments on retinal pigment epithelium (RPE) culture, transplantation of the cells to the subretinal space of animals, especially, the Royal College of Surgeon's (RCS) rat, a model of hereditary retinal degeneration, and observed their effects in preventing photoreceptor cell death. 1) We reviewed recent reports of RPE function in relation to cytokine production and autocrine/paracrine function of these ligands. Some cytokines with strong mitogenic effects as nerve trophic/growth factors were able to rescue photoreceptor cell death in dystrophic, ischemic, and light-damaged retinas in the rats. We transplanted allograft pigmented RPE from Long Evans rats or xenograft, human and bovine RPE into the subretinal space of RCS rats, and could observe the retardation of the photoreceptor cell death. 2) As a source of human transplantable RPE in clinical practice, we could use patients' own RPE cells as autografts or those from aborted human fetus eyes as allografts. At present, we cannot use RPE cells from different species as xenografts. We tried to obtain enough RPE cells for culture in vitro from patients with large or giant retinal tears, but were unsuccessful. Cells were easily obtained from fetus eyes, and could be cultured and transplanted as fresh, primary, or multiple passage cells. We also tried cryopreservation of these cells for up to 3 months. Enzymatic expression of tyrosinase, tyrosinase related protein I and II and some other enzymes was examined by proliferating chain reaction to detect possible transformation during the procedure. The cell characteristics were well preserved. In the future, if these RPE cells could be safely kept and available in deep-frozen condition, we could use them clinically at the appropriate time and in appropriate numbers for patients as an "RPE bank" just like an "eye bank" for corneal transplantation. 3) Immunological reaction is very important if we consider this technique for clinical application. Up to now, in experimental animals, no immunological reaction has been reported even for xenograft human RPE in rats, in funduscope and histological examination, because the intraocular space is an immunologically privileged site. But transplantation of human RPE cells with a collagen sheet into the anterior chamber in rabbits caused a definite reaction detected by suppression of the electroretinogram and macrophage infiltration into the subretinal space, not only in the operated eye but also in the contralateral non-operated eye. These results suggest that we must be cautious in clinical use of heterogeneous RPE transplantation. The expression of MHC class II cells was observed in the course of photoreceptor cell degeneration in the RCS rats but it was suppressed if they were rescued by the transplantation of human cultured RPE in these animals. 4) For clinical application of this technique, autografts are naturally much better than the xeno grafts or allografts. We tried to use iris pigment epithelium (IPE) for transplantation because it consists of pigmented cells of neural origin and enough could be obtained with ease by peripheral iridectomy. We also tried transfection of a vector (pCNX2) or vector-inserted cDNA of rat bFGF into the rat IPE and transplanted into the subretinal space of RCS rats. These transfected cells expressed strong mRNA of bFGF. The photoreceptors were well preserved and immunological reaction could not be detected by funduscopical or histological examinat PMID:9022310
Purpose. The inflammatory response in age-related macular degeneration (AMD) is characterized by mononuclear leukocyte infiltration of the outer blood–retina barrier formed by the retinal pigment epithelium (RPE). A key mechanistic element in AMD progression is RPE dysfunction and apoptotic cell loss. The purpose of this study was to evaluate whether monocyte chemoattractant protein (MCP)-1–activated monocytes induce human RPE apoptosis and whether Ca2+ and reactive oxygen species (ROS) are involved in this process. Methods. A cell-based fluorometric assay was used to measure intracellular Ca2+ concentrations ([Ca2+]i) in RPE cells loaded with fluorescent Ca2+ indicator. Intracellular RPE ROS levels were measured by using the 5- and 6-chloromethyl-2?,7?-dichlorodihydrofluorescence diacetate acetyl ester (CM-H2DCFDA) assay. RPE apoptosis was evaluated by activated caspase-3, Hoechst staining, and apoptosis ELISA. Results. MCP-1–activated human monocytes increased [Ca2+]i, ROS levels, and apoptosis in RPE cells, all of which were inhibited by 8-bromo-cyclic adenosine diphosphoribosyl ribose (8-Br-cADPR), an antagonist of cADPR. Although the ROS scavengers pyrrolidinedithiocarbamate (PDTC) and N-acetylcysteine (NAC) significantly inhibited ROS production and apoptosis induced by activated monocytes, they did not affect induced Ca2+ levels. The induced Ca2+ levels and apoptosis in RPE cells were inhibited by an antibody against cluster of differentiation antigen 14 (CD14), an adhesion molecule expressed by these cells. Conclusions. These results indicate that CD14, Ca2+, and ROS are involved in activated monocyte-induced RPE apoptosis and that cADPR contributes to these changes. Understanding the complex interactions among CD14, cADPR, Ca2+, and ROS may provide new insights and treatments of retinal diseases, including AMD.
Yang, Dongli; Elner, Susan G.; Chen, Xun; Field, Matthew G.; Petty, Howard R.
|This article reviews the research literature on driving and age-related macular degeneration, which is motivated by the link between driving and the quality of life of older adults and their increased collision rate. It addresses the risk of crashes, driving performance, driving difficulty, self-regulation, and interventions to enhance, safety,…
Owsley, Cynthia; McGwin, Gerald, Jr.
Macular edema (ME) is a condition which is usually secondary to an underlying disease process. It is most commonly seen following venous occlusive disease, diabetic retinopathy and posterior segment inflammatory disease. The treatment of ME varies, depending upon the underlying etiology, and has led to varying degrees of success. Traditionally, the main treatment options have included topical and systemic steroids,
Shani Golan; Anat Loewenstein
Diabetes is a serious chronic condition, which increase the risk of cardiovascular diseases, kidney failure and nerve damage leading to amputation. Furthermore the ocular complications include diabetic macular edema, is the leading cause of blindness among adults in the industrialized countries. Today, blindness from diabetic macular edema is largely preventable with timely detection and appropriate interventional therapy. The treatment should include an optimized control of glycemia, arterial tension, lipids and renal status. The photocoagulation laser is currently restricted to focal macular edema in some countries, but due the high cost of intravitreal drugs, the use of laser treatment for focal and diffuse diabetic macular edema (DME), can be valid as gold standard in many countries. The intravitreal anti vascular endothelial growth factor drugs (ranibizumab and bevacizumab), are indicated in the treatment of all types of DME, but the correct protocol for administration should be defined for the different Retina Scientific Societies. The corticosteroids for diffuse DME, has a place in pseudophakic patients, but its complications restricted the use of these drugs for some patients. Finally the intravitreal interface plays an important role and its exploration is mandatory in all DME patients.
This article reviews the research literature on driving and age-related macular degeneration, which is motivated by the link between driving and the quality of life of older adults and their increased collision rate. It addresses the risk of crashes, driving performance, driving difficulty, self-regulation, and interventions to enhance, safety, and considers directions for future research.
Owsley, Cynthia; McGwin, Gerald
Increased exposure to solar ultraviolet B (UVB) radiation may promote age related macular degeneration (AMD). Lutein can protect retinal pigment epithelial (RPE) cells from various oxidative insults but its direct protection against UVB has not been reported. This study aimed to demonstrate protective effects of silk lutein extract against UVB-induced oxidative damage to RPE cells and compared with standard lutein and Trolox, a vitamin E analog. ARPE-19 cells were treated with luteins with and without Trolox prior to UVB exposure. Cell viability and apoptosis were determined by trypan blue staining and caspase-3 activity, respectively. Oxidative damage was evaluated by measuring intracellular reactive oxygen species (ROS), lipid peroxidation, and activities of antioxidant enzymes (superoxide dismutase, glutathione peroxidase and catalase). Levels of lutein remained in culture medium was determined by HPLC. Both luteins reduced cellular ROS levels and lipid peroxidation mediated by UVB, and subsequently increased cell viability and reduced apoptosis. They also restored activities of most tested antioxidant enzymes. Enhancement of lutein antioxidant efficacy was observed in the presence of Trolox. In all these effects, the two lutein preparations had similar effectivenesses. In cell free media, Trolox enhanced the protective effect of lutein probably by reducing its degradation and repairing the oxidized derivatives. Yellow silk cocoon is a potential candidate of lutein for further development as dietary supplement for the prevention of AMD. PMID:23651647
Aimjongjun, Sathid; Sutheerawattananonda, Manote; Limpeanchob, Nanteetip
very popular. This factory produces 25 pigments providing the means of decorating ceramic tiles in a wide palette. Less complete is the range for sanitaryware fired at 1250-1280~ During the 12th five-year plan it is intended to develop pigments of orange, red, beige, and raspberry tones for sanitaryware. What kind of pigments should these be? Apparently, a deep and careful
E. So Cherepanov; O. S. Grum-Grzhimailo; N. S. Belostotskaya; M. So Bibilashvili
\\u000a Pigment dispersion syndrome (PDS) is a unique and fascinating entity. It is far more prevalent, actually by an order of magnitude,\\u000a than previously suspected, comprising 2.45% of the screened Caucasian population in one study . PDS and pigmentary glaucoma (PG) are characterized by disruption of the iris pigment epithelium (IPE) and deposition of\\u000a the dispersed pigment granules throughout the anterior
Purpose The precise mechanism causing outer retinal damage in acute macular neuroretinopathy (AMN) remains unclear. In this study, choroidal blood flow velocity was quantitatively evaluated using laser speckle flowgraphy (LSFG) in a patient with AMN who received systemic corticosteroid therapy. Methods Corticosteroids were systemically administrated across 4 months for an AMN patient. LSFG measurements were taken ten consecutive times before treatment and at 1 week and 1, 3, and 10 months after the onset of therapy. The square blur rate, a quantitative index of relative blood flow velocity, was calculated using LSFG in three regions: Square 1, the macular lesion with findings of severe multifocal electroretinography amplitude reduction, and Squares 2 and 3, funduscopically normal-appearing retinal areas with findings of moderate and mild multifocal electroretinography amplitude reduction, respectively. Results The AMN lesion gradually decreased after treatment and improved results were detected on the Amsler chart, as well as on optical coherence tomography and scanning laser ophthalmoscopy. When the changing rates of the macular flow were compared with the mean square blur rate level before treatment (100%), 14.6%, 24.5%, 12.9%, and 16.3% increases were detected in Square 1 (macular lesion) at 1 week and 1, 3, and 10 months after treatment, respectively. Similarly, in Square 2 (normal-appearing area next to the lesion), 12.6%, 18.6%, 6.7%, and 8.3% increases were also noted at 1 week and 1, 3, and 10 months after treatment, respectively. In Square 3 (normal-appearing area apart from the lesion), 16.0%, 15.1%, 19.1%, and 3.8% increases were measured at 1 week and 1, 3, and 10 months after treatment, respectively. Conclusion In a patient with AMN, choroidal blood flow velocity at the lesion site, which was examined with LSFG, sequentially increased during systemic corticosteroid therapy, together with improvement of visual function. The present findings suggest that choroidal circulation impairment relates to the pathogenesis of AMN, extending over a wider area in the posterior pole than the site of an AMN lesion per se.
Hashimoto, Yuki; Saito, Wataru; Mori, Shohei; Saito, Michiyuki; Ishida, Susumu
Pigmented villonodular synovitis (PVNS) is a destructive proliferative tumoroid disease of the synovial sheath of the joints, bursae, and tendon. The microscopic pattern of PVNS is characterized by mosaicism: compact cell zones alternate with loose few-celled fields. The synovial sheath is hyperplastic; its stroma exhibits hemosiderin and siderophages, as well as histiocytes, lymphocytes, multinucleated giant osteoclasts, foamy and synoviocyte-like cells. Proliferation with destructive growth was noted in PVNS. A distinction is made between focal and diffuse, intraarticular and extraarticular forms of the disease. Early diagnosis of the disease favors effective treatment and prevention of soft tissue and bone destruction and reduces the risk of recurrences. PMID:21313772
Semenova, L A; Radenska-Lopovok, S G
The association of macular detachment with posttraumatic macular hole is a known but rare occurrence. Spontaneously occurring resolution of the detachment and closure of the macular hole has been reported only once in the literature. We describe a similar rare event in a young male, the documentation of which was done serially by microperimetry (MP) and optical coherence tomography (OCT). A 17-year-old male presented with a decrease in vision following a closed globe injury to the left eye. A coexisting macular hole and macular detachment were detected in the affected eye. Serial follow-up with OCT and MP documented complete resolution of the macular hole and the macular detachment within 1 week of presentation. The case highlights that spontaneous resolution of traumatic macular hole and related macular detachment may occur and a waiting period is advisable before undertaking any corrective surgical procedure. The pathophysiologic mechanisms of causation and the resolution of posttraumatic macular hole-related retinal detachment are discussed.
Aalok, Lalit; Azad, Rajvardhan; Sharma, Yog R; Phuljhele, Swati
Purpose: The evaluation of anatomic and visual outcomes in macular hole cases treated with internal limiting membrane (ILM) peeling, brilliant blue (BB), and 23-gauge pars plana vitrectomy (PPV). Materials and methods: Fifty eyes of 48 patients who presented between July 2007 and December 2009 with the diagnosis of stage 2, 3, or 4 macular holes according to Gass Classification who had undergone PPV and ILM peeling were included in this study. Pre- and postoperative macular examinations were assessed with spectral-domain optical coherence tomography. 23 G sutureless PPV and ILM peeling with BB was performed on all patients. Results: The mean age of patients was 63.34 ± 9.6 years. Stage 2 macular hole was determined in 17 eyes (34%), stage 3 in 24 eyes (48%), and stage 4 in 9 eyes (18%). The mean follow-up time was 13.6 ± 1.09 months. Anatomic closure was detected in 46/50 eyes (92%), whereas, in four cases, macular hole persisted and a second operation was not required due to subretinal fluid drainage. At follow-up after 2 months, persistant macular hole was detected in one case and it was closed with reoperation. At 12 months, an increase in visual acuity in 41 eyes was observed, while it remained at the same level in six eyes. In three eyes visual acuity decreased. There was a postoperative statistically significant increase in visual acuity in stage 2 and 3 cases (P < 0.05), however, no increase in visual acuity in stage 4 cases was observed. Conclusion: PPV and ILM peeling in stage 2, 3, and 4 macular hole cases provide successful anatomic outcomes, however, in delayed cases, due to photoreceptor loss, it has no effect on functional recovery. BB, used for clarity of ILM, may be beneficial due to its low retinal toxicity.
Sanisoglu, Huseyin; Sevim, Mehmet Sahin; Aktas, Betul; Sevim, Semra; Nohutcu, Ahmet
...restrictions . Paracoccus pigment may be safely used in the...finished feed, from paracoccus pigment when used alone or in combination...through generally accepted stability testing methods), other...feeds containing paracoccus pigment shall be declared in...
BACKGROUND: Vitamin D plays a critical role in bone metabolism and many cellular and immunological processes. Recent research indicates that concentrations of serum 25-hydroxyvitamin D [25(OH)D], the main indicator of vitamin D status, should be in excess of 75 nmol\\/L. Low levels of 25(OH)D have been associated with several chronic and infectious diseases. Previous studies have reported that many otherwise
Agnes Gozdzik; Jodi Lynn Barta; Hongyu Wu; Dennis Wagner; David E Cole; Reinhold Vieth; Susan Whiting; Esteban J Parra
The natural range of hair and skin colour is a continuous spectrum, controlled by multiple genes in a complex fashion. Many of these genes are as yet unknown, but several key pigmentation genes have been characterised, in particular the melanocortin 1 receptor gene (MC1R). Here, the function and known mutations of MC1R and other human pigmentation genes including ASIP, MATP,
Since the dawn of mankind, cavemen has expressed himself through art. The earliest known cave paintings date to some 32,000 years ago and used 4 colours derived from the earth. These pigments were iron oxides and known as ochres, blacks and whites. All pigments known by the Egyptians, the Greeks, the Romans and Renaissance man were natural and it was
Aim To evaluate the safety of compacted DNA nanoparticles (NPs) in retinal pigment epithelial (RPE) cells. Materials & Methods Enhanced GFP expression cassettes controlled by the RPE-specific vitelloform macular dystrophy promoter were constructed with and without a bacterial backbone and compacted into NPs formulated with polyethylene glycol-substituted lysine 30-mers. Single or double subretinal injections were administered in adult BALB/c mice. Expression levels of enhanced GFP, proinflammatory cytokines and neutrophil/macrophage mediators, and retinal function by electroretinogram were evaluated at different time-points postinjection. Results Immunohistochemistry and real-time PCR demonstrated that NPs specifically transfect RPE cells at a higher efficiency than naked DNA and similar results were observed after the second injection. At 6 h postinjections, a transient inflammatory response was observed in all cohorts, including saline, indicating an adverse effect to the injection procedure. Subsequently, no inflammation was detected in all experimental groups. Conclusion This study demonstrates the safety and efficacy of NP-mediated RPE gene transfer therapy following multiple subretinal administrations.
Han, Zongchao; Koirala, Adarsha; Makkia, Rasha; Cooper, Mark J; Naash, Muna I
Eyes with age-related macular degeneration (AMD) demonstrate accumulation of specific deposits and extracellular matrix (ECM) molecules under the retinal pigment epithelium (RPE). AMD is about two times more prevalent in aging postmenopausal women. Therefore we studied whether 17?-estradiol (E2) modulates the expression and activity of the trimolecular complex (MMP-2, TIMP-2 and MMP-14), molecules which are of major importance for ECM turnover in RPE. We used cell lines isolated from estrogen receptor knockout mice (ERKO) to determine which ER (estrogen receptor) subtype was important for ECM regulation in RPE cells. We found that mouse RPE sheets had higher baseline MMP-2 activity in the presence of ER?. This correlated with higher MMP-2 activity in RPE cell lines isolated from ERKO? mice. Exposure to E2 increased MMP-2 activity in mouse RPE cell lines. In addition E2 increased transcriptional activation of the MMP-2 promoter through a functional Sp1 site which required the presence of ER?, but not ER?. E2 also maintained levels of pro MMP-2, and MMP-14 and TIMP-2 activity after oxidant injury. Since the direct effects of E2 on MMP-2 transcriptional activation and the regulation of the trimolecular complex after oxidant induced injury requires ER?, this receptor subtype may have a role as a potential therapeutic target to prevent changes in activation of MMP-2.
Elliot, Sharon; Catanuto, Paola; Fernandez, Pedro; Espinosa-Heidmann, Diego; Karl, Michael; Korach, Kenneth; Cousins, Scott W.
Interpretation and analysis of retinal angiographic studies has been largely qualitative. Quantitative analysis of pathologic fundus features will facilitate interpretation and potentiate clinical studies where precise image metrology is vital. Fluorescein angiography studies of patients with age- related macular degeneration were digitized. Sequential temporal images were spatially-registered with polynomial warping algorithms, allowing for the construction of a three- dimensional (two spatial and one temporal) angiogram vector. Temporal profiles through spatially-registered, temporally- sequential pixels were computed. Characteristic temporal profiles for fundus background, retinal vasculature, retinal pigment epithelial atrophy, and choroidal neovascular (CNV) membranes were observed, allowing for pixel assignment and fundus feature quantitation. Segmentation and quantitation of fundus features including geographic atrophy and CNV is facilitated by spatio-temporal image analysis.
Berger, Jeffrey W.
Age-related macular degeneration (AMD) is the leading cause of new blindness in the western world and is becoming more of a socio-medical problem as the proportion of the aged population increases. There are multiple efforts underway to better understand this disease process. AMD involves the abnormal retinal pigment epithelium (RPE), drusen formation, photoreceptor atrophy, and choroidal neovascularization. Peroxisome proliferator-activated receptors (PPARs) play an important role in lipid degeneration, immune regulation, regulation of reactive oxygen species (ROSs), as well as regulation of vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and docosahexaenoic acid (DHA). These molecules have all been implicated in the pathogenesis of AMD. In addition, PPAR gamma is expressed in RPE, an essential cell in photoreceptor regeneration and vision maintenance. This review summarizes the interactions between PPAR, AMD-related molecules, and AMD-related disease processes.
Herzlich, Alexandra A.; Tuo, Jingsheng; Chan, Chi-Chao
Ultrahigh resolution optical coherence tomography (OCT) enhances the ability to visualize different intra retinal layers. In age-related macular degeneration (AMD), pathological changes in individual retinal layers, including photoreceptor inner and outer segments and retinal pigment epithelium, can be detected. OCT using spectral / Fourier domain detection enables high speed, volumetric imaging of the macula, which provides comprehensive three-dimensional tomographic and morphologic information. We present a case series of AMD patients, from mild drusen to more advanced geographic atrophy and exudative AMD. Patients were imaged with a research prototype, ultrahigh resolution spectral / Fourier domain OCT instrument with 3.5 ?m axial image resolution operating at 25,000 axial scans per second. These cases provide representative volumetric datasets of well-documented AMD pathologies which could be used for the development of visualization and imaging processing methods and algorithms.
Chen, Yueli; Vuong, Laurel N.; Liu, Jonathan; Ho, Joseph; Srinivasan, Vivek J.; Gorczynska, Iwona; Witkin, Andre J.; Duker, Jay S.; Schuman, Joel; Fujimoto, James G.
The effect of pigment composition on the rheological properties of coating suspensions, containing 5 to 15 wt% of synthetic binder, was studied by using a low-shear rheometer, 0.5 to 100 rpm, at 22°C. The pigments used differed in shape from plate-like (China clay) to spherical-like (CaCO3) particles and were used either individually or in blends. The effects of five types
Samir Y. Elsayad; Fatma Morsy
Age related macular degeneration (AMD) is the most common cause of blindness amongst the elderly. Approximately 10% of AMD patients suffer from an advanced form of AMD characterized by choroidal neovascularization (CNV). Recent evidence implicates a significant role for complement in the pathogenesis of AMD. Activation of complement terminates in the incorporation of the membrane attack complex (MAC) in biological membranes and subsequent cell lysis. Elevated levels of MAC have been documented on choroidal blood vessels and retinal pigment epithelium (RPE) of AMD patients. CD59 is a naturally occurring membrane bound inhibitor of MAC formation. Previously we have shown that membrane bound human CD59 delivered to the RPE cells of mice via an adenovirus vector can protect those cells from human complement mediated lysis ex vivo. However, application of those observations to choroidal blood vessels are limited because protection from MAC- mediated lysis was restricted only to the cells originally transduced by the vector. Here we demonstrate that subretinal delivery of an adenovirus vector expressing a transgene for a soluble non-membrane binding form of human CD59 can attenuate the formation of laser-induced choroidal neovascularization and murine MAC formation in mice even when the region of vector delivery is distal to the site of laser induced CNV. Furthermore, this same recombinant transgene delivered to the intravitreal space of mice by an adeno-associated virus vector (AAV) can also attenuate laser-induced CNV. To our knowledge, this is the first demonstration of a non-membrane targeting CD59 having biological potency in any animal model of disease in vivo. We propose that the above approaches warrant further exploration as potential approaches for alleviating complement mediated damage to ocular tissues in AMD.
Age related macular degeneration (AMD) is the most common cause of blindness amongst the elderly. Approximately 10% of AMD patients suffer from an advanced form of AMD characterized by choroidal neovascularization (CNV). Recent evidence implicates a significant role for complement in the pathogenesis of AMD. Activation of complement terminates in the incorporation of the membrane attack complex (MAC) in biological membranes and subsequent cell lysis. Elevated levels of MAC have been documented on choroidal blood vessels and retinal pigment epithelium (RPE) of AMD patients. CD59 is a naturally occurring membrane bound inhibitor of MAC formation. Previously we have shown that membrane bound human CD59 delivered to the RPE cells of mice via an adenovirus vector can protect those cells from human complement mediated lysis ex vivo. However, application of those observations to choroidal blood vessels are limited because protection from MAC- mediated lysis was restricted only to the cells originally transduced by the vector. Here we demonstrate that subretinal delivery of an adenovirus vector expressing a transgene for a soluble non-membrane binding form of human CD59 can attenuate the formation of laser-induced choroidal neovascularization and murine MAC formation in mice even when the region of vector delivery is distal to the site of laser induced CNV. Furthermore, this same recombinant transgene delivered to the intravitreal space of mice by an adeno-associated virus vector (AAV) can also attenuate laser-induced CNV. To our knowledge, this is the first demonstration of a non-membrane targeting CD59 having biological potency in any animal model of disease in vivo. We propose that the above approaches warrant further exploration as potential approaches for alleviating complement mediated damage to ocular tissues in AMD. PMID:21552568
Cashman, Siobhan M; Ramo, Kasmir; Kumar-Singh, Rajendra
Three unrelated patients with bilateral macular dysplasia ('colobomata') with no relevant family history were found to have absent or substantially abnormal electroretinograms, implying that there was an associated retinal dystrophy. This may suggest that the macular lesions are associated with a global failure of retinal development, with a regional preponderance rather than a purely localised cause such as an intrauterine infection. It is important to distinguish between congenital infections such as toxoplasmosis and developmental macular colobomata, which have a somewhat similar ophthalmoscopic appearance as a cause of bilateral macular abnormalities seen in young children, since they have different implications for genetic advice and future ophthalmic care. Images
Moore, A T; Taylor, D S; Harden, A
The orf162b sequence, the second open reading frame 3? of the reaction center (RC) H protein gene puhA in the Rhodobacter capsulatus photosynthesis gene cluster, is shown to be transcribed from a promoter located 5? of puhA. A nonpolar mutation of orf162b was generated by replacing most of the coding region with an antibiotic resistance cartridge. Although the mutant strain initiated rapid photosynthetic growth, growth slowed progressively and cultures often entered a pseudostationary phase. The amounts of the RC and light harvesting complex I (LHI) in cells obtained from such photosynthetic cultures were abnormally low, but these deficiencies were less severe when the mutant was grown to a pseudostationary phase induced by low aeration in the absence of illumination. The orf162b mutation did not significantly affect the expression of a pufB::lacZ translationally in-frame gene fusion under the control of the puf promoter, indicating normal transcription and translation of RC and LHI genes. Spontaneous secondary mutations in the strain with the orf162b disruption resulted in a bypass of the photosynthetic growth retardation and reduced the level of light harvesting complex II. These results and the presence of sequences similar to orf162b in other species indicate that the Orf162b protein is required for normal levels of the photosynthetic apparatus in purple photosynthetic bacteria.
Aklujkar, Muktak; Harmer, Andrea L.; Prince, Roger C.; Beatty, J. Thomas
A 21-year-old female presented with progressive bilateral visual loss for the past 8 years. The patient had no history of systemic disease, surgery or medications. Complete ophthalmologic examination and topography were performed. On ophthalmic examination, uncorrected visual acuity was counting fingers at 2.5 m (20/50 with pinhole) in the right and left eyes. Both corneas appeared hazy on gross examination. On slit-lamp biomicroscopy, focal grayish-white opacities with indistinct borders were noted in the superficial and deep corneal stroma of both eyes. Both corneas were thin and bulging. Corneal topography showed a pattern consistent with keratoconus. The patient underwent penetrating keratoplasty (PKP). Histopathologic studies after PKP confirmed the diagnosis of macular corneal dystrophy and keratoconus in the same eye. The patient was clinically diagnosed as a case of concurrent macular dystrophy and keratoconus, which is a very rare presentation. PMID:22623870
Mohammad-Rabei, Hossein; Shojaei, Ahmad; Aslani, Mehdi
A 21-year-old female presented with progressive bilateral visual loss for the past 8 years. The patient had no history of systemic disease, surgery or medications. Complete ophthalmologic examination and topography were performed. On ophthalmic examination, uncorrected visual acuity was counting fingers at 2.5 m (20/50 with pinhole) in the right and left eyes. Both corneas appeared hazy on gross examination. On slit-lamp biomicroscopy, focal grayish-white opacities with indistinct borders were noted in the superficial and deep corneal stroma of both eyes. Both corneas were thin and bulging. Corneal topography showed a pattern consistent with keratoconus. The patient underwent penetrating keratoplasty (PKP). Histopathologic studies after PKP confirmed the diagnosis of macular corneal dystrophy and keratoconus in the same eye. The patient was clinically diagnosed as a case of concurrent macular dystrophy and keratoconus, which is a very rare presentation.
Mohammad-Rabei, Hossein; Shojaei, Ahmad; Aslani, Mehdi
PURPOSE: To review a series of patients with age-related macular degeneration undergoing limited macular translocation for the treatment of subfoveal choroidal neovascularization, to determine short-term visual acuity outcomes, to measure amounts of attainable retinal movement, and to identify prognostic factors.METHODS: A retrospective review was conducted on a consecutive series of patients undergoing inferior limited macular translocation with scleral imbrication for
Dante J Pieramici; Eugene De Juan Jr; Gildo Y Fujii; Sandra M Reynolds; Michele Melia; Mark S Humayun; Andrew P Schachat; Craig D Hartranft
Dysfunction and loss of retinal pigment epithelium (RPE) leads to degeneration of photoreceptors in age-related macular degeneration and subtypes of retinitis pigmentosa. Human embryonic stem cells (hESCs) may serve as an unlimited source of RPE cells for transplantation in these blinding conditions. Here we show the directed differentiation of hESCs toward an RPE fate under defined culture conditions. We demonstrate that nicotinamide promotes the differentiation of hESCs to neural and subsequently to RPE fate. In the presence of nicotinamide, factors from the TGF-beta superfamily, which presumably pattern RPE development during embryogenesis, further direct RPE differentiation. The hESC-derived pigmented cells exhibit the morphology, marker expression, and function of authentic RPE and rescue retinal structure and function after transplantation to an animal model of retinal degeneration caused by RPE dysfunction. These results are an important step toward the future use of hESCs to replenish RPE in blinding diseases. PMID:19796620
Idelson, Maria; Alper, Ruslana; Obolensky, Alexey; Ben-Shushan, Etti; Hemo, Itzhak; Yachimovich-Cohen, Nurit; Khaner, Hanita; Smith, Yoav; Wiser, Ofer; Gropp, Michal; Cohen, Malkiel A; Even-Ram, Sharona; Berman-Zaken, Yael; Matzrafi, Limor; Rechavi, Gideon; Banin, Eyal; Reubinoff, Benjamin
The authors presented 6 cases of macular hole retinal detachment in which pars plana vitrectomy with endo-tamponade was performed; in 4 cases SF6 gas and in 2, with PVR silicone oil was used. Retina was completely attached in 4 eyes. Visual acuity 1/50 to 2/50 was achieved in 5 eyes. Follow-up ranged from 5 to 9 months. PMID:8309195
Pikulski, Z; Nawrocki, J; Dziegielewski, K
The methods and results of surgery in 6 cases of retinal detachment with macular hole are presented. In all 6 cases pars plana vitrectomy was performed, in 4 with subsequent SF6 and in 2 with silicone oil tamponade. Retinal attachment was achieved in 4 eyes. Visual acuity 1/50-2/50 was found after surgery in 5 cases. The follow-up ranged from 6 to 9 months. PMID:8022169
Pikulski, Z; Nawrocki, J; Dziegielewski, K
BackgroundRarebit testing implies probing for gaps in the neuro-retinal receptive field matrix, using bright microdots on a dark background. Previous reports have found rarebit testing useful for the detection of macular lesions. In its original implementation, the test requires darkroom facilities and a long test distance (2 m).MethodsA self-contained rarebit test device was realised using a modified miniature data projector
Christina Winther; Lars Frisén
Since the dawn of mankind, cavemen has expressed himself through art. The earliest known cave paintings date to some 32,000 years ago and used 4 colours derived from the earth. These pigments were iron oxides and known as ochres, blacks and whites. All pigments known by the Egyptians, the Greeks, the Romans and Renaissance man were natural and it was not until the 18th century that synthetic pigments were made and widely used. Until that time all art, be it sacred or secular used only natural pigments, of which the preparation of many have been lost or rarely used because of their tedious preparation. As a geologist, a mineralogist and an artist specializing in iconography, I have been able to rediscover 89 natural pigments extracted from minerals. I use these pigments to paint my icons in the traditional Byzantine manner and also to restore old icons, bringing back their glamour and conserving them for years to come. The use of the natural pigments in its proper way also helps to preserve the traditional skills of the iconographer. In the ancient past, pigments were extremely precious. Many took an exceedingly long journey to reach the artists, and came from remote countries. Research into these pigments is the work of history, geography and anthropology. It is an interesting journey in itself to discover that the blue aquamarines came from Afghanistan, the reds from Spain, the greens Africa, and so on. In this contribution I will be describing the origins, preparation and use of some natural pigments, together with their history and provenance. Additionally, I will show how the natural pigments are used in the creation of an icon. Being a geologist iconographer, for me, is a sacrement that transforms that which is earthly, material and natural into a thing of beauty that is sacred. As bread and wine in the Eucharist, water during baptism and oil in Holy Union transmit sanctification to the beholder, natural pigments do the same when one considers an icon. The iconographer uses earthly creations to create divine images: "Thine own of Thine own we offer unto Thee." (Byzantine Liturgy). Thus, by combining geology with art and religion, I can render homage to God through His creation by using minerals of the Planet Earth, as natural pigments in painting His image.
Kelekian, Lena, ,, Lady
Chromobacterium violaceum sepsis is rare but associated with a high mortality rate. We report a fatal case of C. violaceum sepsis in a 6 years old Venezuelan indian boy. Clinical manifestations were fever and swelling in the right inguinal region. The initial diagnosis was an appendicular plastron. Appendicectomy was performed and during surgery a right psoas abscess was identified that resulted culture positive for pigmented C. violaceum. Blood cultures were positive for a pigmented and non pigmented C. violaceum strain. Imipenem and amikacin were administered despite of which the child died 9 days after hospital admission. PMID:17989847
Guevara, Armando; Salomón, Marlly; Oliveros, María; Guevara, Esmirna; Guevara, Milarys; Medina, Laida
Inorganic pigments have been utilized by mankind since ancient times, and are still widely used to colour materials exposed to elevated temperatures during processing or application. Indeed, in the case of glasses, glazes and ceramics, there is no alternative to inorganic pigments for colouring. However, most inorganic pigments contain heavy metals or transition metals that can adversely effect the environment and human health if critical levels are exceeded. Cadmium-based pigments in particular are a cause of concern: although the pigments are not toxic due to their very low solubility in water and dilute mineral acids, cadmium itself is toxic and can enter the environment in a bioavailable form through waste-disposal sites and incineration plants. This has led to regulations, based on the precautionary principle, that strongly restrict the use of cadmium pigments. And even though recent assessments have concluded that the risk to humans or the environment might be not as significant as originally feared, a strong demand for inherently safer substitutes remains. Here we demonstrate that solid solutions of the perovskites CaTaO 2N and LaTaON2 constitute promising candidates for such substitutes: their brilliance, tinting strength, opacity, dispersability, light-fastness and heat stability rival that of the cadmium pigments, while their colour can be tuned through the desired range, from yellow through orange to deep red, by simple composition adjustments. Because all the constituent elements are harmless, this perovskite-based inorganic pigment system seems a promising replacement that could eliminate one of the sources for cadmium emissions to the environment and some of the remaining concerns about pigment safety.
Jansen, M.; Letschert, H. P.
Inorganic pigments have been utilized by mankind since ancient times, and are still widely used to colour materials exposed to elevated temperatures during processing or application. Indeed, in the case of glasses, glazes and ceramics, there is no alternative to inorganic pigments for colouring. However, most inorganic pigments contain heavy metals or transition metals that can adversely effect the environment and human health if critical levels are exceeded. Cadmium-based pigments in particular are a cause of concern: although the pigments are not toxic due to their very low solubility in water and dilute mineral acids, cadmium itself is toxic and can enter the environment in a bioavailable form through waste-disposal sites and incineration plants. This has led to regulations, based on the precautionary principle, that strongly restrict the use of cadmium pigments. And even though recent assessments have concluded that the risk to humans or the environment might be not as significant as originally feared, a strong demand for inherently safer substitutes remains. Here we demonstrate that solid solutions of the perovskites CaTaO2N and LaTaON2 constitute promising candidates for such substitutes: their brilliance, tinting strength, opacity, dispersability, light-fastness and heat stability rival that of the cadmium pigments, while their colour can be tuned through the desired range, from yellow through orange to deep red, by simple composition adjustments. Because all the constituent elements are harmless, this perovskite-based inorganic pigment system seems a promising replacement that could eliminate one of the sources for cadmium emissions to the environment and some of the remaining concerns about pigment safety. PMID:10801123
The pyridinium bis-retinoid, A2-E, has been discovered as one of the major autofluorescent components of retinal pigment epithelial lipofuscin. Due to its chemical characteristics, A2-E may contribute to cellular and molecular changes leading to age-related macular degeneration. Because A2-E is the first lipofuscin component that has been identified, purified, and its structure analysed, it represents an important marker molecule for
J.-J REINBOTH; K GAUTSCHI; K MUNZ; G. E ELDRED; C. H. E REMÉ
Background The changes of perifoveal capillary blood flow velocity (BFV), visual acuity, and retinal thickness after pars plana vitrectomy\\u000a (PPV) have been unclear in patients with branch retinal vein occlusion (BRVO) and macular edema.\\u000a \\u000a \\u000a \\u000a Methods In a prospective study, PPV was performed on six eyes of six consecutive BRVO patients with macular edema (two women and four\\u000a men; mean age: 66.3?±?5.0 years). Patients
Hidetaka Noma; Hideharu Funatsu; Kumi Sakata; Tatsuya Mimura; Sadao Hori
Purpose To report the formation of a lamellar macular hole (LMH) in four eyes with chronic cystoid macular edema (CME) associated\\u000a with retinal vein occlusion (RVO).\\u000a \\u000a \\u000a \\u000a \\u000a Methods We reviewed retrospectively the medical records of four patients with chronic CME associated with RVO, in whom LMH formation\\u000a was observed by a series of examinations with optical coherence tomography.\\u000a \\u000a \\u000a \\u000a \\u000a Results All eyes showed a large
Kayoko TsukadaAkitaka Tsujikawa; Akitaka Tsujikawa; Tomoaki Murakami; Ken Ogino; Nagahisa Yoshimura
Age-related macular degeneration (AMD) is the most common reason of visual impairment in the elderly in the Western countries. The degeneration of retinal pigment epithelial cells (RPE) causes secondarily adverse effects on neural retina leading to visual loss. The aging characteristics of the RPE involve lysosomal accumulation of lipofuscin and extracellular protein aggregates called "drusen". Molecular mechanisms behind protein aggregations are weakly understood. There is intriguing evidence suggesting that protein SQSTM1/p62, together with autophagy, has a role in the pathology of different degenerative diseases. It appears that SQSTM1/p62 is a connecting link between autophagy and proteasome mediated proteolysis, and expressed strongly under the exposure to various oxidative stimuli and proteasomal inhibition. ELAVL1/HuR protein is a post-transcriptional factor, which acts mainly as a positive regulator of gene expression by binding to specific mRNAs whose corresponding proteins are fundamental for key cellular functions. We here show that, under proteasomal inhibitor MG-132, ELAVL1/HuR is up-regulated at both mRNA and protein levels, and that this protein binds and post-transcriptionally regulates SQSTM1/p62 mRNA in ARPE-19 cell line. Furthermore, we observed that proteasomal inhibition caused accumulation of SQSTM1/p62 bound irreversibly to perinuclear protein aggregates. The addition of the AMPK activator AICAR was pro-survival and promoted cleansing by autophagy of the former complex, but not of the ELAVL1/HuR accumulation, indeed suggesting that SQSTM1/p62 is decreased through autophagy-mediated degradation, while ELAVL1/HuR through the proteasomal pathway. Interestingly, when compared to human controls, AMD donor samples show strong SQSTM1/p62 rather than ELAVL1/HuR accumulation in the drusen rich macular area suggesting impaired autophagy in the pathology of AMD. PMID:23922739
Viiri, Johanna; Amadio, Marialaura; Marchesi, Nicoletta; Hyttinen, Juha M T; Kivinen, Niko; Sironen, Reijo; Rilla, Kirsi; Akhtar, Saeed; Provenzani, Alessandro; D'Agostino, Vito Giuseppe; Govoni, Stefano; Pascale, Alessia; Agostini, Hansjurgen; Petrovski, Goran; Salminen, Antero; Kaarniranta, Kai
We present the preliminary results of the first stage of the project AO-594, which comprises the development and calibration of algorithms for photosynthetic pigment mapping in Spanish reservoirs. In the years 2001-2002, an extensive field campaign was made in 36 reservoirs and lakes in order to obtain a database of Rrs spectra (400-1000 nm), photosynthetic pigments concentration and phytoplankton composition. The sampled water bodies cover a wide range of environmental conditions, trophic levels and phytoplankton communities. As a first approach in algorithm development, we have explored the relationships between ratios of MERIS bands and pigment concentrations through simple linear regression analysis. The bands have been selected based on the spectral properties of each pigment and a peak analysis of the Rrs spectra. For chlorophyll a, we have found a very good linear relationship (R2 =0.919) using the ratio between bands 9 and 7. Similar results are found using band 8 instead of 7. In any case, the model derived for the whole range of concentrations (0-500 mg m3 ) fails for low values (<15 mg m-3 ). Possible solutions include the use of - non-linear models or the use of two different models depending on the ratio values. For cyanobacteria detection, the ratio between bands 9 and 6 (the later centred at 620 nm) shows a good correlation (R2 =0.723) with phycocyanin concentration measured fluorometrically, and better (R2 =0.945) with zeaxanthin measured using HPLC. The correlation of other indicator pigments with MERIS band ratios is less strong, but is still possible to develop algorithms accurate enough for bloom monitoring. We also discuss the problems found with the L2 MERIS reflectance imagery that we have tried to use for model calibration. We present the results of the study carried on six reservoirs in northeastern Spain. In a date coincident with a MERIS image (June 19th, 2003) we have collected pigment concentration and reflectance data measured from a boat and 10 m resolution imagery for the 15 MERIS bands acquired with an airborne CASI-2 sensor. This three-level data has allowed us to calculate a new set of reflectance MERIS bands from the L1B imagery and compare them with the L2 imagery. The comparison could be useful for modifying the current atmospheric correction algorithms applied for L2 data generation, which we have observed that frequently fail in inland waters.
Peńa-Martinez, R.; Domínguez-Gómez, J.-A.; de Hoyos, C.; Ruiz-Verdú, A.
Objective To assess high-speed ultrahigh-resolution optical coherence tomography (OCT) image resolution, acquisition speed, image quality, and retinal coverage for the visualization of macular pathologies. Design Retrospective cross-sectional study. Participants Five hundred eighty-eight eyes of 327 patients with various macular pathologies. Methods High-speed ultrahigh-resolution OCT images were obtained in 588 eyes of 327 patients with selected macular diseases. Ultrahigh-resolution OCT using Fourier/spectral domain detection achieves ~3-?m axial image resolutions, acquisition speeds of ~25 000 axial scans per second, and >3 times finer resolution and >50 times higher speed than standard OCT. Three scan protocols were investigated. The first acquires a small number of high-definition images through the fovea. The second acquires a raster series of high-transverse pixel density images. The third acquires 3-dimensional OCT data using a dense raster pattern. Three-dimensional OCT can generate OCT fundus images that enable precise registration of OCT images with the fundus. Using the OCT fundus images, OCT results were correlated with standard ophthalmoscopic examination techniques. Main Outcome Measures High-definition macular pathologies. Results Macular holes, age-related macular degeneration, epiretinal membranes, diabetic retinopathy, retinal dystrophies, central serous chorioretinopathy, and other pathologies were imaged and correlated with ophthalmic examination, standard OCT, fundus photography, and fluorescein angiography, where applicable. High-speed ultrahigh-resolution OCT generates images of retinal pathologies with improved quality, more comprehensive retinal coverage, and more precise registration than standard OCT. The speed preserves retinal topography, thus enabling the visualization of subtle changes associated with disease. High-definition high-transverse pixel density OCT images improve visualization of photoreceptor and pigment epithelial morphology, as well as thin intraretinal and epiretinal structures. Three-dimensional OCT enables comprehensive retinal coverage, reduces sampling errors, and enables assessment of 3-dimensional pathology. Conclusions High-definition 3-dimensional imaging using high-speed ultrahigh-resolution OCT improves image quality, retinal coverage, and registration. This new technology has the potential to become a useful tool for elucidating disease pathogenesis and improving disease diagnosis and management.
Srinivasan, Vivek J.; Wojtkowski, Maciej; Witkin, Andre J.; Duker, Jay S.; Ko, Tony H.; Carvalho, Mariana; Schuman, Joel S.; Kowalczyk, Andrzej; Fujimoto, James G.
Scientific analysis of painted antique objects provides us with information about the pigments used in earlier periods of history. Beginning in prehistoric times, coloured earths and minerals were used exclusively until the 3rd millenium B.C. when an extensive production of artificial pigments started. Following Egyptian Blue, a potassium copper chloride, cobalt blue, and a cobalt aluminium oxide was invented but used only over a short period, until it was reinvented 200 years ago. In the Greecian and Roman times the palette was considerably enlarged by the use of other coloured minerals and artificially prepared pigments.
Amalgam tattoo, the most common exogenous oral pigmentation, can sometimes be confused with melanotic lesions, being then biopsied. We present the clinicopathological characteristics of 6 biopsied cases (5 females and 1 male) of oral amalgam pigmentation. The most common location was the gingival mucosa, followed by the buccal and palatal mucosa. Morphology and distribution (stromal, perivascular, perineural, endomysial) of pigmentation was variable; there was only 1 case with fibrous capsular reaction and likewise only a single case of granulomatous foreign body reaction. Morphological variability is conditioned by the timing and amount of the pigment deposit, which is often associated with infiltration by mast cells (CD117+), as well as overexpression of metallothionein and HLA-DR at different tissue levels. PMID:22502738
Vera-Sirera, Beatriz; Risueńo-Mata, Presentación; Ricart-Vayá, José M; Baquero Ruíz de la Hermosa, Carmen; Vera-Sempere, Francisco
Human induced pluripotent stem cells (iPSCs) have great promise for cellular therapy, but it is unclear if they have the same potential as human embryonic stem cells (hESCs) to differentiate into specialized cell types. Ocular cells such as the retinal pigmented epithelium (RPE) are of particular interest because they could be used to treat degenerative eye diseases, including age-related macular degeneration and retinitis pigmentosa. We show here that iPSCs generated using Oct4, Sox2, Nanog, and Lin28 can spontaneously differentiate into RPE cells, which can then be isolated and cultured to form highly differentiated RPE monolayers. RPE derived from iPSCs (iPS-RPE) were analyzed with respect to gene expression, protein expression, and rod outer segment phagocytosis, and compared with cultured fetal human RPE (fRPE) and RPE derived from hESCs (hESC-RPE). iPS-RPE expression of marker mRNAs was quantitatively similar to that of fRPE and hESC-RPE, and marker proteins were appropriately expressed and localized in polarized monolayers. Levels of rod outer segment phagocytosis by iPS-RPE, fRPE, and hESC-RPE were likewise similar and dependent on integrin alpha v beta 5. This work shows that iPSCs can differentiate into functional RPE that are quantitatively similar to fRPE and hESC-RPE and further supports the finding that iPSCs are similar to hESCs in their differentiation potential. PMID:19658190
Buchholz, David E; Hikita, Sherry T; Rowland, Teisha J; Friedrich, Amy M; Hinman, Cassidy R; Johnson, Lincoln V; Clegg, Dennis O
Purpose. The authors showed previously that parafoveal rods, but not cones, decrease during the course of adulthood in donor eyes that were screened to exclude the grossly visible macular drusen and pigmentary disturbances typical of age-related macular degeneration (AMD). Because AMD begins in the parafovea, this selective loss of rods actually may be subclinical AMD not yet visible in the
Christine A. Curcio; Nancy E. Medeiros; C. Leigh Millican
Objective: To evaluate visual outcomes following macu- lar translocation with 360° peripheral retinectomy in pa- tients with subfoveal choroidal neovascularization sec- ondary to age-related macular degeneration. Methods: In a prospective study, 15 consecutive pa- tients with large subfoveal choroidal neovascularization underwent macular translocation with 360° peripheral retinectomy and silicone oil tamponade. Preoperative and postoperative photographs and fluorescein angiograms were obtained
James C. Lai; Deborah J. Lapolice; Sandra S. Stinnett; Carsten H. Meyer; Luz M. Arieu; Melissa A. Keller; Cynthia A. Toth
Introduction: To evaluate the effect of ?-lipoic acid (ALA) on the occurrence of diabetic macular edema. Methods: Randomized, double-blind, placebo-controlled, multicenter, multinational study. Patients were randomized to the treatment group with 600 mg ALA per day or the placebo group. Every 6 months stereo fundus photographs, HbA1c levels, and an ophthalmological examination were documented. The primary endpoint was the occurrence
Christos Haritoglou; Joachim Gerss; Hans P. Hammes; Anselm Kampik; Michael W. Ulbig
Purpose To investigate the incidence of reticular macular disease (RMD), a subphenotype of age-related macular degeneration (AMD), in multilobular geographic atrophy (GA) and its relation to GA progression. Methods 157 eyes of 99 subjects with AMD, primary GA, and good-quality autofluorescence (AF) and/or infrared (IR) images were classified into unilobular GA (1 lesion) or multilobular GA (>= 2 distinct and/or coalescent lesions). 34 subjects (50 eyes) had serial imaging. We determined the spatiotemporal relationships of RMD to GA and GA progression rates in 5 macular fields. Results 144/157 (91.7%) eyes had multilobular GA, 95.8% of which exhibited RMD. In subjects with serial imaging, the mean GA growth rate significantly differed between the unilobular and multilobular groups (0.40 mm2 /yrvs. 1.30 mm2 /yr, p< 0.001). Of the macular fields in these eyes, 77.1% of fields with RMD at baseline showed subsequent GA progression, while 53.4% of fields without RMD showed progression (p <0.001). Percentage of fields with RMD significantly correlated with GA progression rate(p=0.01). Conclusion AF and IR imaging demonstrates that RMD is nearly always present with multilobular GA in AMD. Further, GA lobules frequently develop in areas of RMD, suggesting progression of a single underlying disease process.
Xu, Luna; Blonska, Anna M.; Pumariega, Nicole M.; Bearelly, Srilaxmi; Sohrab, Mahsa A.; Hageman, Gregory S.; Smith, R. Theodore
PurposeMacular holes cause retinal detachments in highly myopic eyes. Because degenerative macular changes often coexist, biomicroscopic evaluation of macular hole status after retinal reattachment is sometimes difficult. We studied macular holes with retinal detachment after vitrectomy using optical coherence tomography and evaluated the anatomic status of the hole and factors associated with anatomic success.
Yasushi Ikuno; Kaori Sayanagi; Tetsuro Oshima; Fumi Gomi; Shunji Kusaka; Motohiro Kamei; Masahito Ohji; Takashi Fujikado; Yasuo Tano
Nine patients with maculopathy (macular holes, macular cysts, and lamellar holes) and ten patients with optic neuritis were examined in order to determine changes in the visual evoked potential (VEP) in response to pattern-reversal stimulation. Eyes with lamellar holes had normal P100 latency, but eyes with macular cysts and macular holes had prolonged P100 latency. Eyes with optic neuritis exhibited
L. N. Johnson; R. D. Yee; R. S. Hepler; D. A. Martin
Human skin pigmentation is the product of two clines produced by natural selection to adjust levels of constitutive pigmentation to levels of UV radiation (UVR). One cline was generated by high UVR near the equator and led to the evolution of dark, photoprotective, eumelanin-rich pigmentation. The other was produced by the requirement for UVB photons to sustain cutaneous photosynthesis of vitamin D3 in low-UVB environments, and resulted in the evolution of depigmented skin. As hominins dispersed outside of the tropics, they experienced different intensities and seasonal mixtures of UVA and UVB. Extreme UVA throughout the year and two equinoctial peaks of UVB prevail within the tropics. Under these conditions, the primary selective pressure was to protect folate by maintaining dark pigmentation. Photolysis of folate and its main serum form of 5-methylhydrofolate is caused by UVR and by reactive oxygen species generated by UVA. Competition for folate between the needs for cell division, DNA repair, and melanogenesis is severe under stressful, high-UVR conditions and is exacerbated by dietary insufficiency. Outside of tropical latitudes, UVB levels are generally low and peak only once during the year. The populations exhibiting maximally depigmented skin are those inhabiting environments with the lowest annual and summer peak levels of UVB. Development of facultative pigmentation (tanning) was important to populations settling between roughly 23° and 46° , where levels of UVB varied strongly according to season. Depigmented and tannable skin evolved numerous times in hominin evolution via independent genetic pathways under positive selection.
Jablonski, Nina G.; Chaplin, George
X-ray phase studies made it possible to trace the structural inversions~in the crystalline pigments at the sintering temperature [i]. Together with the intermediate compounds formed in the process of firing the batches at various temperatures, as a result of the solid-phase reaction in pigment synthesis, we noted the presence of neodymium orthosilicate Nd~Si30~2 (3.23; 3.12; 2.83; 1.96; 1.78 A) with
E. Sh. Kharashvili
The terms pigmentary mosaicism or patterned dyspigmentation describe a spectrum of clinical findings that range from localized areas of dyspigmentation with no systemic findings to widespread dyspigmentation with associated neurologic, musculoskeletal, and cardiac abnormalities, and other sequelae that can lead to early demise. Given this wide spectrum, these patients must be approached with caution, but with the understanding that most who have localized pigmentary anomalies, such as segmental pigmentary disorder (SegPD) seem to have no systemic manifestations. These patients can be approached in many different ways, but generally children with more widespread dyspigmentation, and any with associated abnormalities or not meeting neurodevelopmental milestones, should be evaluated closely. Children with any red flags warrant subspecialty referral, and all children deserve close clinical follow-up with their primary care physician to ensure they meet all of their developmental milestones. Fortunately, parents can be reassured that most children with SegPD, and many with more widespread patterned pigmentation, are otherwise healthy. PMID:20888462
Purpose. To report the outcomes after primary intravitreal pegaptanib sodium in patients with diabetic macular edema (DME). Methods. We conduced a retrospective analysis of eyes with DME treated with primary intravitreal pegaptanib sodium (Macugen) (intravitreal pegaptanib group). The results were compared with the ones of eyes treated with intravitreal pegaptanib sodium associated with macular laser photocoagulation (combined treatment group), and the ones of eyes treated with primary macular laser photocoagulation (macular laser photocoagulation group). Results. For the intravitreal pegaptanib group (13 eyes), we found significant changes in mean best-corrected visual acuity (BCVA) and reductions in mean central macular thickness (CMT) at the last follow-up visit (P = .0014 and P = .0001). For the macular laser photocoagulation group (15 eyes), we found no statistically significant changes in mean BCVA and CMT at the last follow-up visit (P > .05). For the combined treatment group (12 eyes), we found no significant changes in mean BCVA at the last follow-up visit (P > .05) despite significant reductions in mean CMT (P = .0188). Conclusion. Intravitreal pegaptanib treatment alone may be superior to macular laser photocoagulation alone and to combined intravitreal pegaptanib treatment associated with macular laser photocoagulation in patients with DME.
Querques, G.; Bux, A. V.; Fusco, A. R.; Iaculli, C.; Delle Noci, N.
ObjectiveTo measure the change in vision and visual outcomes at 12 months after macular translocation with 360° retinectomy (MT360) and silicone oil tamponade in patients with bilateral vision loss resulting from subfoveal choroidal neovascular membranes in age-related macular degeneration (AMD).
Prithvi Mruthyunjaya; Sandra S. Stinnett; Cynthia A. Toth
Fluorescent bisretinoids, such as A2E and all-trans-retinal dimer, form as a by-product of vitamin A cycling in retina and accumulate in retinal pigment epithelial (RPE) cells as lipofuscin pigments. These pigments are implicated in pathological mechanisms involved in several vision-threatening diseases including age-related macular degeneration. Efforts to understand damaging events initiated by these bisretinoids have revealed that photoexcitation of A2E by wavelengths in the visible spectrum leads to singlet oxygen production and photooxidation of A2E. Here we have employed liquid chromatography coupled to electrospray ionization mass spectrometry together with tandem mass spectrometry (MS/MS), to demonstrate that A2E also undergoes photooxidation-induced degradation and we have elucidated the structures of some of the aldehyde-bearing cleavage products. Studies in which A2E was incubated with a singlet oxygen generator yielded results consistent with a mechanism involving bisretinoid photocleavage at sites of singlet molecular oxygen addition. We provide evidence that one of the products released by A2E photodegradation is methylglyoxal, a low molecular weight reactive dicarbonyl with the capacity to form advanced glycation end products. Methylglyoxal is already known to be generated by carbohydrate and lipid oxidation; this is the first report of its production via bisretinoid photocleavage. It is significant that AGE-modified proteins are detected in deposits (drusen) that accumulate below RPE cells in vivo; drusen have been linked to age-related macular degeneration pathogenesis. Whereas various processes play a role in drusen formation, these findings are indicative of a contribution from lipofuscin photooxidation in RPE. PMID:20368460
Wu, Yalin; Yanase, Emiko; Feng, Xidong; Siegel, Marshall M; Sparrow, Janet R
Although frequently performed, laser removal of pigmented lesions still contains certain controversial issues. Epidermal pigmented lesions include solar lentigines, ephelides, café au lait macules and seborrheic keratoses. Dermal lesions include melanocytic nevi, blue nevi, drug induced hyperpigmentation and nevus of Ota and Ito. Some lesions exhibit both an epidermal and dermal component like Becker's nevus, postinflammatory hyperpigmentations, melasma and nevus spilus. Due to the wide absorption spectrum of melanin (500-1100 nm), several laser systems are effective in removal of pigmented lesions. These lasers include the pigmented lesion pulsed dye laser (510 nm), the Q-switched ruby laser (694 nm), the Q-switched alexandrite laser (755 nm) and the Q-switched Nd:YAG laser (1064 nm), which can be frequency-doubled to produce visible green light with a wavelength of 532 nm. The results of laser therapy are usually successful. However, there are still many controversies regarding the use of lasers in treating certain pigmented lesions. Actually, the essential question in removing pigmented lesions with lasers is whether the lesion has atypical features or has a malignant potential. Dermoscopy, used as a routine first-level diagnostic technique, is helpful in most cases. If there is any doubt whether the lesion is benign, then a biopsy for histologic evaluation is obligatory. PMID:20887701
Bukvi? Mokos, Zrinka; Lipozen?i?, Jasna; Ceovi?, Romana; Stulhofer Buzina, Daška; Kostovi?, Krešimir
Purpose To investigate the efficacy of intravitreal bevacizumab for the treatment of idiopathic macular telangiectasia (IMT).\\u000a \\u000a \\u000a \\u000a Methods Ten eyes of eight consecutive patients with IMT were studied. Four eyes had type 1, and six had type 2 IMT according to Yannuzzi’s\\u000a classification. All patients were treated with intravitreal bevacizumab (1.25 mg) injections at baseline. Monthly fundus and\\u000a optical coherence tomography (OCT) examinations
Yoko Matsumoto; Mitsuko Yuzawa
The introduction of spectral-domain optical coherence tomography (SD-OCT) has improved the clinical value for assessment of the eyes with macular disease. This article reviews the advances of SD-OCT for the diagnostic of various macular diseases. These include vitreomacular traction syndrome, cystoid macular edema\\/diabetic macular edema, epiretinal membranes, full-thickness macular holes, lamellar holes, pseudoholes, microholes, and schisis from myopia. Besides offering
Sebastian Wolf; Ute Wolf-Schnurrbusch
Bright light illumination (photostress) of the macula produces a negative after-image in the form of a central scotoma. The time needed for restoring normal visual acuity function, "macular recovery time," may be measured using a nyctometer. We have measured the recovery in 30 normal men, aged 18 to 23 years, at sea level and at 8,000 ft (n = 10), 15,000 ft (n = 10), and 18,000 ft (n = 10) of simulated altitudes in a low pressure chamber. The degree of initial recovery (the first 30-40 s) was unaffected by hypoxia equivalent to 8,000, 15,000, and 18,000 ft. The recovery at 2 min was impaired by hypoxia at an altitude of 18,000 ft (p = 0.009) but not at 8,000 ft or 15,000 ft. The initial phase of recovery may represent the neural phase of macular function and appears to be more resistant to hypoxia than the recovery at 2 min, the latter probably being dominated by photochemical recovery. The study establishes a critical level of hypoxia where complete recovery of macular sensitivity is not achieved. PMID:2604673
Brinchmann-Hansen, O; Myhre, K
The effectiveness of latent fingerprint development techniques is heavily influenced by the physical and chemical properties of the deposition surface. The use of powder suspensions is increasing for development of prints on a range of surfaces. We demonstrate that carbon powder suspension development on polymers is detrimentally affected by the presence of common white pigment, titanium dioxide. Scanning electron microscopy demonstrates that patches of the compound are clearly associated with increased levels of powder adhesion. Substrates with nonlocalized titanium dioxide content also exhibit increased levels of carbon powder staining on a surface-wide basis. Secondary ion mass spectrometry and complementary techniques demonstrate the importance of levels of the pigment within the top 30 nm. The association is independent of fingermark deposition and may be related to surface energy variation. The detrimental effect of the pigment is not observed with small-particle reagent (MoS2 SPR) or cyanoacrylate (superglue) fuming techniques that exploit different development mechanisms. PMID:23822671
Bacon, Simon R; Ojeda, Jesus J; Downham, Rory; Sears, Vaughn G; Jones, Benjamin J
Optical coherence tomography (OCT) is an interferometry-based imaging modality that generates high-resolution cross-sectional images of the retina. Circumpapillary retinal nerve fibre layer (cpRNFL) and optic disc assessments are the mainstay of glaucomatous structural measurements. However, because these measurements are not always available or precise, it would be useful to have another reliable indicator. The macula has been suggested as an alternative scanning location for glaucoma diagnosis. Using time-domain (TD) OCT, macular measurements have been shown to provide good glaucoma diagnostic capabilities. Performance of cpRNFL measurement was generally superior to macular assessment. However, macular measurement showed better glaucoma diagnostic performance and progression detection capability in some specific cases, which suggests that these two measurements may be combined to produce a better diagnostic strategy. With the adoption of spectral-domain OCT, which allows a higher image resolution than TD-OCT, segmentation of inner macular layers becomes possible. The role of macular measurements for detection of glaucoma progression is still under investigation. Improvement of image quality would allow better visualisation, development of various scanning modes would optimise macular measurements, and further refining of the analytical algorithm would provide more accurate segmentation. With these achievements, macular measurement can be an important surrogate for glaucomatous structural assessment. PMID:23018425
Sung, Kyung Rim; Wollstein, Gadi; Kim, Na Rae; Na, Jung Hwa; Nevins, Jessica E; Kim, Chan Yun; Schuman, Joel S
Purpose. To describe the complete sequence of the progressive vasculopathy in macular telangiectasia type 2.?Methods. This is a report of a case demonstrating the complete vasogenic sequence in macular telangiectasia type 2 over the course of 15 years, and representative images from a collective of 150 patients with macular telangiectasia type 2 employing fundus photography, fluorescein angiography, and optical coherence tomography.?Results. Macular telangiectasia may progress along a predictable vasogenic sequence which consists of nonproliferative stages, characterized by temporal loss of macular luteopigment and inner retinal volume loss in the absence of vascular changes, followed by a progressive proliferative vasculopathy, first involving the deep capillary plexus with eventual extension of the vascular changes circumferentially in the inner retinal capillary plexus. Late proliferative stages may become indistinguishable from advanced neovascular age-related macular degeneration.?Conclusions. While it is rare to observe the complete vasogenic sequence of macular telangiectasia type 2, a classification into nonproliferative and proliferative stages can be established, and may prove helpful as the mechanisms driving the pathogenic process through those stages are identified. PMID:23138663
Engelbert, Michael; Yannuzzi, Lawrence A
Dark brown granular pigment was found consistently in macrophages in the deep aspect of adult Peyer's patches. Tissue sections from intestinal resections of 35 patients with a variety of pathologic diagnoses and of seven postmortem cases with no evidence of gastrointestinal disease were examined for the presence of this pigment. It was found in all patients over the age of 6 years (34 cases) but was not found in any children below that age (eight cases). Scanning electron microscopy with secondary and backscattered electron imaging and x-ray energy spectroscopy were performed on routine histologic sections. The pigmented macrophages contained aluminum and silicon, diffusely present throughout the cytoplasm, and numerous discrete foci of titanium. Pigment containing these same elements has also been found around dilated submucosal lymphatics, in mesenteric lymph nodes, and in some transmural inflammatory aggregates of Crohn's disease. The pigment probably is derived from the diet and actively taken up by Peyer's patches, which are able to incorporate inert particulate matter.
Shepherd, N.A.; Crocker, P.R.; Smith, A.P.; Levison, D.A.
Studies in this laboratory have previously shown that hydroxytyrosol, the major antioxidant polyphenol in olives, protects ARPE-19 human retinal pigment epithelial cells from oxidative damage induced by acrolein, an environmental toxin and endogenous end product of lipid oxidation, that occurs at increased levels in age-related macular degeneration lesions. A proposed mechanism for this is that protection by hydroxytyrosol against oxidative stress is conferred by the simultaneous activation of two critically important pathways, viz., induction of phase II detoxifying enzymes and stimulation of mitochondrial biogenesis. Cultured ARPE-19 cells were pretreated with hydroxytyrosol and challenged with acrolein. The protective effects of hydroxytyrosol on key factors of mitochondrial biogenesis and phase II detoxifying enzyme systems were examined. Hydroxytyrosol treatment simultaneously protected against acrolein-induced inhibition of nuclear factor-E2-related factor 2 (Nrf2) and peroxisome proliferator-activated receptor coactivator 1 alpha (PPARGC1?) in ARPE-19 cells. The activation of Nrf2 led to activation of phase II detoxifying enzymes, including ?-glutamyl-cysteinyl-ligase, NADPH (nicotinamide adenine dinucleotide phosphate)-quinone-oxidoreductase 1, heme-oxygenase-1, superoxide dismutase, peroxiredoxin and thioredoxin as well as other antioxidant enzymes, while the activation of PPARGC1? led to increased protein expression of mitochondrial transcription factor A, uncoupling protein 2 and mitochondrial complexes. These results suggest that hydroxytyrosol is a potent inducer of phase II detoxifying enzymes and an enhancer of mitochondrial biogenesis. Dietary supplementation of hydroxytyrosol may contribute to eye health by preventing the degeneration of retinal pigment epithelial cells induced by oxidative stress. PMID:20149621
Zhu, Lu; Liu, Zhongbo; Feng, Zhihui; Hao, Jiejie; Shen, Weili; Li, Xuesen; Sun, Lijuan; Sharman, Edward; Wang, Ying; Wertz, Karin; Weber, Peter; Shi, Xianglin; Liu, Jiankang
Age-related macular degeneration (AMD) is the most common cause of blindness among the elderly. AMD patients have elevated levels of membrane attack complex (MAC) in their choroidal blood vessels and retinal pigment epithelium (RPE). MAC forms pores in cell membranes. Low levels of MAC result in an elevation of cytokine release such as vascular endothelial growth factor (VEGF) that promotes the formation of choroidal neovascularization (CNV). High levels of MAC result in cell lysis and RPE degeneration is a hallmark of advanced AMD. The current standard of care for CNV associated with wet AMD is intravitreal injection of anti-VEGF molecules every 4 to 12 weeks. Such injections have significant side effects. Recently, it has been found that membrane pore-forming proteins such as ?-haemolysin can mediate their toxic effects through auto- and paracrine signaling and that complement-induced lysis is amplified through ATP release followed by P2X receptor activation. We hypothesized that attenuation of P2X receptor activation may lead to a reduction in MAC deposition and consequent formation of CNV. Hence, in this study we investigated topical application of the purinergic P2X antagonist Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) as a potential treatment for AMD. We found that 4.17 µM PPADS inhibited formation of HUVEC master junctions and master segments by 74.7%. In a human complement mediated cell lysis assay, 104 µM PPADS enabled almost complete protection of Hepa1c1c7 cells from 1% normal human serum mediated cell lysis. Daily topical application of 4.17 mM PPADS for 3 days attenuated the progression of laser induced CNV in mice by 41.8% and attenuated the deposition of MAC at the site of the laser injury by 19.7%. Our data have implications for the future treatment of AMD and potentially other ocular disorders involving CNV such as angioid streaks, choroidal rupture and high myopia. PMID:24130789
Birke, Kerstin; Lipo, Erion; Birke, Marco T; Kumar-Singh, Rajendra
Age-related macular degeneration (AMD) is the most common cause of blindness among the elderly. AMD patients have elevated levels of membrane attack complex (MAC) in their choroidal blood vessels and retinal pigment epithelium (RPE). MAC forms pores in cell membranes. Low levels of MAC result in an elevation of cytokine release such as vascular endothelial growth factor (VEGF) that promotes the formation of choroidal neovascularization (CNV). High levels of MAC result in cell lysis and RPE degeneration is a hallmark of advanced AMD. The current standard of care for CNV associated with wet AMD is intravitreal injection of anti-VEGF molecules every 4 to 12 weeks. Such injections have significant side effects. Recently, it has been found that membrane pore-forming proteins such as ?-haemolysin can mediate their toxic effects through auto- and paracrine signaling and that complement-induced lysis is amplified through ATP release followed by P2X receptor activation. We hypothesized that attenuation of P2X receptor activation may lead to a reduction in MAC deposition and consequent formation of CNV. Hence, in this study we investigated topical application of the purinergic P2X antagonist Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) as a potential treatment for AMD. We found that 4.17 µM PPADS inhibited formation of HUVEC master junctions and master segments by 74.7%. In a human complement mediated cell lysis assay, 104 µM PPADS enabled almost complete protection of Hepa1c1c7 cells from 1% normal human serum mediated cell lysis. Daily topical application of 4.17 mM PPADS for 3 days attenuated the progression of laser induced CNV in mice by 41.8% and attenuated the deposition of MAC at the site of the laser injury by 19.7%. Our data have implications for the future treatment of AMD and potentially other ocular disorders involving CNV such as angioid streaks, choroidal rupture and high myopia.
Birke, Kerstin; Lipo, Erion; Birke, Marco T.; Kumar-Singh, Rajendra
This study examines the differences in spectral absorption properties between the maculae of patients with active neovascular macular degeneration and those with early age related maculopathy (ARM). Patients attending for management of neovascular age related macular degeneration (AMD) underwent multispectral imaging with a system comprising of a modified digital fundus camera coupled with a 250-W tungsten-halogen lamp and a liquid crystal fast-tuneable filter. Images were obtained at 8 wavelengths between 496 and 700 nm. Aligned images were used to generate a DLA (differential light absorption, a measure of spectral absorption properties) map of the macular area. DLA maps were generated for both eyes of 10 sequential patients attending for anti-vascular endothelial growth factor injections. Each of these patients had active leaking neovascular AMD in one eye and early ARM or milder disease in the fellow eye. Eyes with neovascular AMD demonstrated lower average levels of DLA compared with their fellow eyes with early ARM (p=0.037, t test). The significant difference in DLA demonstrates the potential of multispectral imaging for differentiating the two pathologies non-invasively. PMID:23137662
Balaskas, Konstantinos; Nourrit, Vincent; Dinsdale, Michelle; Henson, David B; Aslam, Tariq
Purpose To determine the risk of progression to advanced age-related macular degeneration (AMD) conferred by reticular pseudodrusen (RPD), an imaging presentation of reticular macular disease (RMD), in high-risk fellow eyes of subjects with AMD and unilateral choroidal neovascularization (CNV) in a large prospective study. Design Cohort study. Participants 271 subjects with AMD; 94 with RPD and 177 without RPD. Methods We studied images from a cohort of 271 subjects with AMD in the NAT 2 Study, a 3-year prospective study of subjects with unilateral CNV and large soft drusen in the fellow eye. The fellow eye, at high risk for developing advanced AMD, was the study eye. There were 5 visits per subject. Imaging at each visit consisted of color, red free, and blue light photography and fluorescein angiography. We analyzed the images for the presence of RPD, following disease progression throughout the 3-year study. Main Outcome Measures The development of advanced AMD (CNV or geographic atrophy). Results For the 271 subjects who completed the full 3-year study, there was a significantly higher rate of advanced AMD (56% or 53/94) in fellow eyes with RPD at any visit compared to eyes without RPD (32% or 56/177; p = 7.7E-05, ?2 test; relative risk (RR) 1.8; 95% confidence interval (CI) 1.4–2.4). The chance of developing advanced AMD in the fellow eye in females with RPD (66%) was more than double compared to females without RPD (30%, p = 5.1E-06, RR 2.2, 95% CI 1.6–3.1). Conclusion To our knowledge, this is the first comprehensive prospective study of reticular macular disease (RMD), a distinct clinical phenotype of AMD which includes RPD. It provides strong confirmation that RMD, a disease entity with stereotypical presentations across imaging modalities, is associated with high risk of progression to advanced AMD, perhaps on an inflammatory or vascular basis. RMD deserves wider recognition and consideration by clinicians caring for patients with AMD.
Pumariega, Nicole M.; Smith, R. Theodore; Sohrab, Mahsa A.; LeTien, Valerie; Souied, Eric H.
We study excitation energy transfer in a simple model of a photosynthetic complex. The model, described by the Lindblad equation, consists of pigments interacting via dipole-dipole interaction. The overlapping of pigments induces an on-site energy disorder, providing a mechanism for blocking the excitation transfer. Based on the average efficiency as well as the robustness of random configurations of pigments, we calculate the optimal number of pigments that should be enclosed in a pigment-protein complex of a given size. The results suggest that a large fraction of pigment configurations are efficient as well as robust if the number of pigments is properly chosen. We compare the optimal results of the model to the structure of pigment-protein complexes as found in nature, finding good agreement.
Jesenko, Simon; Žnidari?, Marko
ABSTRACT Purpose To determine whether cultured fetal human retinal pigment epithelium (RPE) cells can attach and differentiate on submacular Bruch’s membrane from donors over age 55. Methods Differential debridements of Bruch’s membrane were performed to expose three different surfaces: the RPE basement membrane, the superficial inner collagenous layer (ICL) directly below the RPE basement membrane, and the deeper ICL. Approximately 3,146 cells/mm2 were seeded onto these Bruch’s membrane explants and cultured for 1 or 7 days. Explants were bisected and examined histologically or analyzed with scanning electron microscopy. Nuclear density counts were performed on stained sections. Morphology and cell density were compared to those of cells seeded onto bovine corneal endothelial cell–extracellular matrix (BCE-ECM). Results Compared to cells seeded onto BCE-ECM at similar density, cell coverage and cellular morphology were poor at both time points. Unlike cells on BCE-ECM, cell density remained the same or decreased with time. In general, cell morphology on all surfaces worsened by day 7 compared to day 1. Although cells were more pigmented on RPE basement membrane and deep ICL at day 7, poor cellular morphology indicated the remaining cells were not well differentiated. An explant from a donor with large soft drusen showed the poorest resurfacing at day 7 in organ culture. Conclusions These data indicate that aged submacular human Bruch’s membrane does not support transplanted RPE survival and differentiation. The formation of localized RPE defects, cell death, and worsening cellular morphology on aged Bruch’s membrane suggest that modification of Bruch’s membrane may be necessary in patients with age-related macular degeneration receiving RPE transplants to prevent graft failure.
Gullapalli, Vamsi K; Sugino, Ilene K; Van Patten, Yancy; Shah, Sumit; Zarbin, Marco A
Breakdown of the inner endothelial blood-retinal barrier (BRB), as occurs in diabetic retinopathy, age-related macular degeneration, retinal vein occlusions, uveitis and other chronic retinal diseases, results in vasogenic edema and neural tissue damage, causing loss of vision. The central mechanism of altered BRB function is a change in the permeability characteristics of retinal endothelial cells caused by elevated levels of growth factors, cytokines, advanced glycation end products, inflammation, hyperglycemia and loss of pericytes. Subsequently, paracellular but also transcellular transport across the retinal vascular wall increases via opening of endothelial intercellular junctions and qualitative and quantitative changes in endothelial caveolar transcellular transport, respectively. Functional changes in pericytes and astrocytes, as well as structural changes in the composition of the endothelial glycocalyx and the basal lamina around BRB endothelium further facilitate BRB leakage. As Starling's rules apply, active transcellular transport of plasma proteins by the BRB endothelial cells causing increased interstitial osmotic pressure is probably the main factor in the formation of macular edema. The understanding of the complex cellular and molecular processes involved in BRB leakage has grown rapidly in recent years. Although appropriate animal models for human conditions like diabetic macular edema are lacking, these insights have provided tools for rational design of drugs aimed at restoring the BRB as well as for design of effective transport of drugs across the BRB, to treat the chronic retinal diseases such as diabetic macular edema that affect the quality-of-life of millions of patients. PMID:23416119
Klaassen, Ingeborg; Van Noorden, Cornelis J F; Schlingemann, Reinier O
PURPOSE: We report cross-sectional images of diabetic macular edema and correlation between tomographic features and visual acuity with best correction by means of optical coherence tomography.METHOD: In a prospective study, optical coherence tomography was performed in 59 eyes of 42 patients with diabetic macular edema and in 10 eyes of 10 normal control subjects.RESULTS: Optical coherence tomography showed three patterns
Tomohiro Otani; Shoji Kishi; Yasuhiro Maruyama
Purpose A peripapillary detachment in pathologic myopia (PDPM) appears as a yellowish-orange lesion around the optic disc in highly\\u000a myopic eyes. We report a case in which a macular retinal detachment (RD) accompanied a PDPM. Method A case report was used in this study. Results The right eye in a 48-year-old man showed a macular RD and a PDPM. Fluorescein
Noriaki Shimada; Kyoko Ohno-Matsui; Yoichi Iwanaga; Takashi Tokoro; Manabu Mochizuki
Wet age-related macular degeneration which incidence increases year by year is a blinding eye disease, but current clinical methods of treatment on this disease are limited and the outcome is not ideal. Recent studies have found abnormally high expression of tissue factors which are targets for the treatment of wet age-related macular degeneration to achieve a certain effect in the choroidal neovascularization. Related literatures are reviewed as following.
Wang, Guan-Feng; Zou, Xiu-Lan
Zinc-ferrite pigment was prepared by solid-state reaction. A mixture of ?-Fe2O3 and ZnO in a molar ratio of 1:1 was fired at 1,200°C. X-ray diffraction measurements proved that the reacted material crystallized into a spinal structure. Measurement of the pigment specification and properties were carried out according to standard international methods. The pigment extract and the extract of the pigment-linseed
Y. M. Abu Ayana; S. M. El-Sawy; S. H. Salah
The Monascus species has been used in foods for thousands of years in China. In this study, 10 azaphilone pigments, including four yellow and six orange pigments, were isolated from the fermented rice and dioscorea of Monascus purpureus NTU 568. By employing lipopolysaccharide (LPS)-stimulated murine macrophage RAW 264.7 cells, we determined the inhibitory activities of these pigments on nitric oxide (NO) production. As a result, four orange pigments, monaphilols A-D, showed the highest activities (IC50 = 1.0-3.8 ?M), compared with the other two orange pigments, monascorubrin (IC50 > 40 ?M) and rubropunctatin (IC50 = 21.2 ?M), and the four yellow pigments ankaflavin (IC50 = 21.8 ?M), monascin (IC50 = 29.1 ?M), monaphilone A (IC50 = 19.3 ?M), and monaphilone B (IC50 = 22.6 ?M). Using Western blot and ELISA kits, we found that treatments with 30 ?M of the yellow pigments and 5 ?M of the orange pigments could down-regulate the protein expression of inducible nitric oxide synthase (iNOS) and suppress the production of tumor necrosis factor-? (TNF-?), interleukin-1? (IL-1?), and interleukin-6 (IL-6). We also used two animal experiments to evaluate the anti-inflammatory effects of these pigments. In a 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema model, eight of these pigments (0.5 mg/ear) could prevent ear edema against TPA administrations on the ears of BALB/c mice. In an LPS-injection mice model, several of these pigments (10 mg/kg) could inhibit the NO, TNF-?, IL-1?, and IL-6 levels in the plasma of BALB/c mice. As concluded from the in vitro and in vivo studies, six azaphilonoid pigments, namely, ankaflavin, monaphilone A, and monaphilols A-D, showed high potential to be developed into chemopreventive foods or drugs against inflammation-associated diseases. PMID:23458314
Hsu, Li-Chuan; Liang, Yu-Han; Hsu, Ya-Wen; Kuo, Yao-Haur; Pan, Tzu-Ming
Contemporary variation in skin pigmentation is the result of hundreds of thousands years of human evolution in new and changing environments. Previous studies have identified several genes involved in skin pigmentation differences among African, Asian, and European populations. However, none have examined skin pigmentation variation among Indigenous American populations, creating a critical gap in our understanding of skin pigmentation variation. This study investigates signatures of selection at 76 pigmentation candidate genes that may contribute to skin pigmentation differences between Indigenous Americans and Europeans. Analysis was performed on two samples of Indigenous Americans genotyped on genome-wide SNP arrays. Using four tests for natural selection--locus-specific branch length (LSBL), ratio of heterozygosities (lnRH), Tajima's D difference, and extended haplotype homozygosity (EHH)--we identified 14 selection-nominated candidate genes (SNCGs). SNPs in each of the SNCGs were tested for association with skin pigmentation in 515 admixed Indigenous American and European individuals from regions of the Americas with high ground-level ultraviolet radiation. In addition to SLC24A5 and SLC45A2, genes previously associated with European/non-European differences in skin pigmentation, OPRM1 and EGFR were associated with variation in skin pigmentation in New World populations for the first time. PMID:22198722
Quillen, Ellen E; Bauchet, Marc; Bigham, Abigail W; Delgado-Burbano, Miguel E; Faust, Franz X; Klimentidis, Yann C; Mao, Xianyun; Stoneking, Mark; Shriver, Mark D
Diabetic macular oedema (DMO) is a significant cause of visual loss in the working population. Focal/grid photocoagulation remains an effective treatment for DMO and the benchmark to which clinicians compare other newer treatment modalities. There are, however, patients who do not respond adequately or who are refractory to laser photocoagulation. This has led to the development of newer treatments such as the intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors as well as intravitreal corticosteroid releasing delivery systems. Cataract formation and raised intraocular pressure remain the major disadvantages of corticosteroid use. There is mounting evidence that intravitreal VEGF inhibitors with or without combined laser photocoagulation will become the gold standard treatment for DMO.
Ross, Adam H.; Clare Bailey, C.
Purpose: Although important progress has been made in understanding age-related macular degeneration (AMD), management of the disease continues to be a challenge. AMD research has led to a widening of available treatment options and improved prognostic perspectives. This essay reviews these treatment options. Design: Interpretative essay. Methods: Literature review and interpretation. Results: Current treatments to preserve vision in patients with non-exudative AMD include antioxidant vitamins and mineral supplementations. Exudative AMD is currently most often treated monthly with anti-VEGF intravitreal injections. However, investigators are beginning to experiment with combination therapy and surgical approaches in an attempt to limit the number of treatment and reduce the financial burden on the health care system. Conclusion: By better understanding the basis and pathogenesis of AMD, newer therapies will continue to be developed that target specific pathways in patients with AMD, with the hoped for outcome of better management of the disease and improved visual acuity.
Hubschman, Jean Pierre; Reddy, Shantan; Schwartz, Steven D
The authors assess the corrosion resistance, crystal structure, chemical composition and color properties of a variety of zircon-based materials used as pigments and protective coatings for ceramic tiles. The constituents of these materials include, apart from zircon, iron oxides, vanadium oxides, and the sulfides, selenides and tellurides of cadmium. The effects of these constituents on the structural behavior of the
E. S. Cherepanov; O. S. Grum-Grzhimailo; N. S. Belostotskaya; M. S. Bibilashvili
The utilization of techniques used in Materials Science for the characterization of artefacts of interest for cultural heritage is getting more and more attention nowadays. One of the products of the ancient Maya chemistry is the “Maya blue” pigment, made with natural indigo and palygorskite. This pigment is different from any other pigment used in other parts of the world.
M. Sánchez del Río; A. Sodo; S. G. Eeckhout; T. Neisius; P. Martinetto; E. Dooryhee; C. Reyes-Valerio
Thin-layer chromatographic procedures using silica gel and glucose have been employed for the examination of the pigments of twenty-three species of marine phytoplankton, drawn from a number of classes. Several new xanthophylls have been found including one similar to fucoxanthin which is the principal pigment in an, as yet, undescribed member of the Haptophyceae. The pigment array of a species
J. P. Riley; T. R. S. Wilson
Aim: Selective retinal pigment epithelium (RPE) laser treatment is a new technique which selectively damages the RPE while sparing the neural retina. One difficulty is the inability to visualise the laser lesions. The aim of the study was to investigate whether fundus autofluorescence (AF) is changed because of the RPE damage, and thus might be used for treatment control. Additionally, the clinical course of patients with various macular diseases was evaluated. Methods: 26 patients with macular diseases (diabetic maculopathy (DMP), soft drusen maculopathy (AMD), and central serous retinopathy (CSR)) were treated and followed up for at least 6 months. Treatment was performed with a train of repetitive short laser pulses (800 ns) of a frequency doubled Nd:YAG laser (parameters: 532 nm, 50 and 500 pulses at 100 and 500 Hz, retinal spot diameter 200 ?m, pulse energies 75–175 ?J). AF was excited by 488 nm and detected by a barrier filter at 500 nm (HRA, Heidelberg Engineering, Germany). Patients were examined by ophthalmoscopy, fluorescein angiography, and autofluorescence measurements at various times after treatment (10 minutes, 1 hour, 1 and 6 weeks, 3, 6, and 12 months). Results: Fluorescein angiography showed leakage from the irradiated areas for about 1 week after treatment. None of the laser lesions was ophthalmoscopically visible during treatment. Identification of the lesions was possible by AF imaging showing an intensity decay in the irradiated area in 22 out of 26 patients, predominantly in patients with CSR and AMD. Lesions could be identified 10 minutes after treatment as hypoautofluorescent spots, which were more pronounced 1 hour later. During follow up the laser spots became hyperautofluorescent. In patients with DMP some AF images were less helpful because of diffuse oedema and larger retinal thickness. In these cases ICG angiography was able to confirm therapeutic success very well. Most of the patients have had benefit from the treatment, with best results obtained for CSR patients. Conclusion: Imaging of non-visible selective RPE laser effects can be achieved by AF measurements predominantly in patients without retinal oedema. Therefore, AF may replace invasive fluorescein angiography in many cases to verify therapeutic laser success. Selective laser treatment has the potential to improve the prognosis of macular diseases without the risk of laser scotomas.
Framme, C; Brinkmann, R; Birngruber, R; Roider, J
We present polarization-sensitive optical coherence tomography (PS-OCT) for quantitative assessment of retinal pathologies in age-related macular degeneration (AMD). On the basis of the polarization scrambling characteristics of the retinal pigment epithelium, novel segmentation algorithms were developed that allow one to segment pathologic features such as drusen and atrophic zones in dry AMD as well as to determine their dimensions. Results from measurements in the eyes of AMD patients prove the ability of PS-OCT for quantitative imaging based on the retinal features polarizing properties. Repeatability measurements were performed in retinas diagnosed with drusen and geographic atrophy in order to evaluate the performance of the described methods. PS-OCT appears as a promising imaging modality for three-dimensional retinal imaging and ranging with additional contrast based on the structures’ tissue-inherent polarization properties.
Baumann, Bernhard; Gotzinger, Erich; Pircher, Michael; Sattmann, Harald; Schutze, Christopher; Schlanitz, Ferdinand; Ahlers, Christian; Schmidt-Erfurth, Ursula; Hitzenberger, Christoph K.
?-Secretase (BACE1) is a major drug target for combating Alzheimer's disease (AD). Here we show that BACE1(-/-) mice develop significant retinal pathology including retinal thinning, apoptosis, reduced retinal vascular density and an increase in the age pigment, lipofuscin. BACE1 expression is highest in the neural retina while BACE2 was greatest in the retinal pigment epithelium (RPE)/choroid. Pigment epithelial-derived factor, a known regulator of ?-secretase, inhibits vascular endothelial growth factor (VEGF)-induced in vitro and in vivo angiogenesis and this is abolished by BACE1 inhibition. Moreover, intravitreal administration of BACE1 inhibitor or BACE1 small interfering RNA (siRNA) increases choroidal neovascularization in mice. BACE1 induces ectodomain shedding of vascular endothelial growth factor receptor 1 (VEGFR1) which is a prerequisite for ?-secretase release of a 100?kDa intracellular domain. The increase in lipofuscin following BACE1 inhibition and RNAI knockdown is associated with lysosomal perturbations. Taken together, our data show that BACE1 plays a critical role in retinal homeostasis and that the use of BACE inhibitors for AD should be viewed with extreme caution as they could lead to retinal pathology and exacerbate conditions such as age-related macular degeneration. PMID:22903875
Cai, Jun; Qi, Xiaoping; Kociok, Norbert; Skosyrski, Sergej; Emilio, Alonso; Ruan, Qing; Han, Song; Liu, Li; Chen, Zhijuan; Bowes Rickman, Catherine; Golde, Todd; Grant, Maria B; Saftig, Paul; Serneels, Lutgarde; de Strooper, Bart; Joussen, Antonia M; Boulton, Michael E
The aim of this study was to evaluate macular thickness parameters in glaucoma patients and to compare them to normal subjects using Optical Coherence Tomography (OCT). This prospective, observational study included 20 primary open angle glaucoma patients (POAG) and 20 healthy subjects in control group. Exclusion criteria were diabetes and other macular pathology, like age-related macular degeneration, macular oedema, central serous retinopathy and high myopia >4.00 dsph. OCT imaging of peripapillar retina and macular area were performed using Cirrus HD OCT In these two groups of patients we analyzed changes of macular thickness parameters (central subfield thickness, macular volume, and average macular thickness). The group of glaucoma patients had decreased values of the two macular thickness parameters: macular volume and average macular thickness, compared to control group. There was no difference in central macular thickness, presumably because of the absence of the ganglion cells in this layer. Macular imaging can be a useful additional method to determine glaucoma status and has a potential for tracking glaucoma progression. PMID:22856228
Barisi?, Freja; Sicaja, Ana Jurin; Ravli?, Maja Malenica; Novak-Laus, Katia; Ivekovi?, Renata; Mandi?, Zdravko
Summary There is no doubt that visual impressions of body form and color are important in the interactions within and between human communities. Remarkably, it is the levels of just one chemically inert and stable visual pigment known as melanin that is responsible for producing all shades of humankind. Major human genes involved in its formation have been identified largely
Richard A. Sturm; Neil F. Box; Michele Ramsay
Various amino acid derivatives of monascus pigments were synthesized. The effects of pigment derivatives on the pigment adsorption ratio, electrophoretic mobility (EPM) of bacterial cells, and antibacterial activity were investigated under varying conditions of pigment type, pigment concentration, pH, and ionic strength. Two hydrophobic and two hydrophilic derivatives were selected as model pigments. There was a close relationship between the
Chulyoung Kim; Heeyong Jung; Jong Hoon Kim; Chul Soo Shin
Purpose To describe the prevalence and signs of early and late age-related macular degeneration (AMD) in an old cohort. Design Population based cohort study Participants We included 5,272 persons 66 years and older, randomly sampled from the Reykjavik area. Methods Fundus images were taken through dilated pupils using a 45°digital camera and were graded for drusen size, type, area, increased retinal pigment, retinal pigment epithelial depigmentation, neovascular lesions and geographic atrophy using the modified Wisconsin Age-Related Maculopathy Grading System. Main outcome measure Age-related macular degenerationin an old cohort. Results Mean age of participants was 76 years. The prevalence of early AMD was 12.4% (95% confidence interval [CI] 11.0–13.9) for those 66–74 year old and 36% (95% CI 30.9–41.1) for those 85 years and older. The prevalence of exudative AMD was 3.3% (95% CI 2.8–3.8) and for pure geographic atrophy 2.4% (95% CI 2.0–2.8). The highest prevalence for late AMD was among those 85 years and older 11.4% (95% CI 8.2–14.5) for exudative AMD and 7.6% (95% CI 4.8–10.4) for pure geographic atrophy. Conclusion Persons 85 years and older have 10-fold higher prevalence of late AMD than those 70–74 years old. The high prevalence of late AMD in the oldest age-group and expected increase of old people in the western world in coming years call for improved preventive measures and novel treatments.
Jonasson, Fridbert; Arnarsson, Arsaell; Eiriksdottir, Gudny; Harris, Tamara B.; Launer, Lenore J.; Meuer, Stacy M; Klein, Barbara E; Klein, Ronald; Gudnason, Vilmundur; Cotch, Mary Frances
In diabetic retinopathy, vision loss is usually secondary to macular edema, which is thought to depend on the functional integrity of the blood-retina barrier. The levels of advanced glycation end products in the vitreous correlate with the progression of diabetic retinopathy. Natriuretic peptides (NP) are expressed in the eye and their receptors are present in the retinal pigment epithelium (RPE). Here, we investigated the effect of glycated-albumin (Glyc-alb), an advanced glycation end product model, on RPE-barrier function and the ability of NP to suppress this response. Transepithelial electrical resistance (TEER) measurements were used to assess the barrier function of ARPE-19 and human fetal RPE (hfRPE) monolayers. The monolayers were treated with 0.1-100 ?g/ml Glyc-alb in the absence or presence of 1 pM to 100 nM apical atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), or C-type natriuretic peptide (CNP). Glyc-alb induced a significant reduction in TEER within 2 hours. This response was concentration-dependent (EC(50)= 2.3 ?g/ml) with a maximal reduction of 40 ± 2% for ARPE-19 and 27 ± 7% for hfRPE at 100 ?g/ml 6 hours post-treatment. One hour pretreatment with ANP, BNP, or CNP blocked the reduction in TEER induced by Glyc-alb (100 ?g/ml). The suppression of the Glyc-alb response by NP was dependent on the generation of cyclic guanosine monophosphate and exhibited a rank order of agonist potency consistent with the activation of natriuretic-peptide-receptor-2 (NPR2) subtype (CNP > BNP ? ANP). Our data demonstrate that Glyc-alb is effective in reducing RPE-barrier function, and this response is suppressed by NP. Moreover, these studies support the idea that NPR2 agonists can be potential candidates for treating retinal edema in diabetic patients. PMID:23086231
Dahrouj, Mohammad; Alsarraf, Oday; Liu, Yueying; Crosson, Craig E; Ablonczy, Zsolt
Purpose:? Accumulation of bisretinoids as lipofuscin in retinal pigment epithelial (RPE) cells is implicated in the pathogenesis of some blinding diseases including age-related macular degeneration (AMD). To identify genes whose expression may change under conditions of bisretinoid accumulation, we investigated the differential gene expression in RPE cells that had accumulated the lipofuscin fluorophore A2E and were exposed to blue light (430?nm). Methods:? A2E-laden RPE cells were exposed to blue light (A2E/430?nm) at various time intervals. Cell death was quantified using Dead Red staining, and RNA levels for the entire genome was determined using DNA microarrays (Affymetrix GeneChip Human Genome 2.0 Plus). Array results for selected genes were confirmed by real-time reverse-transcriptase polymerase chain reaction. Results:? Principal component analysis revealed that the A2E-laden RPE cells irradiated with blue light were clearly distinguishable from the control samples. We found differential regulation of genes belonging to the following functional groups: transcription factors, stress response, apoptosis and immune response. Among the last mentioned were downregulation of four genes that coded for proteins that have an inhibitory effect on the complement cascade: (complement factor H, complement factor H-related 1, complement factor I and vitronectin) and of two belonging to the classical pathway (complement component 1, s subcomponent and complement component 1, r subcomponent). Conclusion:? This study demonstrates that blue light irradiation of A2E-laden RPE cells can alter the transcription of genes belonging to different functional pathways including stress response, apoptosis and the immune response. We suggest that these molecules may be associated to the pathogenesis of AMD and can potentially serve as future therapeutic targets. PMID:23742627
van der Burght, Barbro W; Hansen, Morten; Olsen, Jřrgen; Zhou, Jilin; Wu, Yalin; Nissen, Mogens H; Sparrow, Janet R
The Macular Photocoagulation Study (MPS) is a set of randomized, controlled clinical trials designed to evaluate the effectiveness of laser photocoagulation of neovascular lesions, secondary to age-related (senile) macular degeneration (AMD or SMD), ocula...
Importance Optical coherence tomography (OCT) findings of temporal macular thinning are important in the diagnosis and prognosis of X-linked Alport syndrome (XLAS). Objectives To report OCT findings and severity of temporal macular thinning in a cohort with XLAS and to correlate these and other ocular findings with mutation genotype. Design Patients with XLAS underwent genotyping for COL4A5 mutations and complete eye examinations with retinal imaging using spectral domain OCT and fundus photography. Temporal macular thinning was calculated from OCT measurements by comparing the ratio of the retinal thickness of the temporal to the nasal subfields with a published normative database. Setting University departments of ophthalmology and nephrology. Participants Thirty-two patients from 24 families. Main Outcome and Measures Temporal thinning index calculated from spectral domain OCT scans. Results All study patients had a mutation associated with the X-linked COL4A5 gene. Eleven different mutations were identified. Eleven of 32 patients (34%) expressed the L1649R mutation. Of a total of 63 eyes with available OCT scans, 44 (70%) had severe pathological temporal macular thinning. The L1649R mutation was associated with the least amount of severe temporal macular thinning and later onset of renal failure. Conclusions and Relevance Temporal macular thinning is a prominent sign associated with XLAS, suggesting that OCT measurements are essential in the diagnosis and prognosis of the disease. The L1649R mutation in the COL4A5 gene causes a relatively mild form of XLAS characterized by late-onset renal failure and less frequent, severe temporal macular thinning relative to other COL4A5 mutations. The pathological basis for the retinal abnormalities of XLAS remains to be established.
Ahmed, Faisal; Kamae, Kandon K.; Jones, Denise J.; DeAngelis, Margaret M.; Hageman, Gregory S.; Gregory, Martin C.; Bernstein, Paul S.
Objective: To determine whether fingolimod, an oral sphingosine-1-phosphate receptor modulator approved for treatment of multiple sclerosis (MS), generally leads to increased retinal tissue volume. Methods: In this longitudinal observational study, we compared changes in macular volume on spectral-domain optical coherence tomography (OCT) between consecutive patients with MS who initiated fingolimod and a matched reference cohort of patients with MS never exposed to the drug. The primary reference cohort was matched based on time interval between OCT examinations. A secondary reference cohort was matched based on age and disease duration. Change in macular volume within each group was analyzed using the paired t test. Change in macular volume between groups was examined using multiple linear regression. Results: Macular volume increased by a mean of 0.025 mm3 (95% confidence interval [CI] +0.017 to +0.033, p < 0.001) in the 30 patients with MS who initiated fingolimod over a mean follow-up time of 5 months (SD 3). Macular volume did not significantly change over a mean follow-up time of 6 months (SD 4) in a comparison group of 30 patients with MS never treated with fingolimod (mean change of ?0.003 mm3, 95% CI ?0.009 to +0.004, p = 0.47). Overall, 74% of eyes in the fingolimod-treated group exhibited an increase in macular volume vs 37% of eyes in the comparison group. Conclusion: Initiation of fingolimod in MS is associated with a modest, relatively rapid increase in macular volume.
Nolan, Rachel; Gelfand, Jeffrey M.
The age-dependent accumulation of lipofuscin in the retinal pigment epithelium (RPE) has been associated with the development of retinal diseases, particularly age-related macular degeneration and Stargardt disease. A major component of lipofuscin is the bis-retinoid N-retinylidene-N-retinylethanolamine (A2E). The current model for the formation of A2E requires photoactivation of rhodopsin and subsequent release of all-trans-retinal. To understand the role of light exposure in the accumulation of lipofuscin and A2E, we analyzed RPEs and isolated rod photoreceptors from mice of different ages and strains, reared either in darkness or cyclic light. Lipofuscin levels were determined by fluorescence imaging, whereas A2E levels were quantified by HPLC and UV-visible absorption spectroscopy. The identity of A2E was confirmed by tandem mass spectrometry. Lipofuscin and A2E levels in the RPE increased with age and more so in the Stargardt model Abca4(-/-) than in the wild type strains 129/sv and C57Bl/6. For each strain, the levels of lipofuscin precursor fluorophores in dark-adapted rods and the levels and rates of increase of RPE lipofuscin and A2E were not different between dark-reared and cyclic light-reared animals. Both 11-cis- and all-trans-retinal generated lipofuscin-like fluorophores when added to metabolically compromised rod outer segments; however, it was only 11-cis-retinal that generated such fluorophores when added to metabolically intact rods. The results suggest that lipofuscin originates from the free 11-cis-retinal that is continuously supplied to the rod for rhodopsin regeneration and outer segment renewal. The physiological role of Abca4 may include the translocation of 11-cis-retinal complexes across the disk membrane. PMID:22570475
Boyer, Nicholas P; Higbee, Daniel; Currin, Mark B; Blakeley, Lorie R; Chen, Chunhe; Ablonczy, Zsolt; Crouch, Rosalie K; Koutalos, Yiannis
In the aging human eye, oxidative damage and accumulation of pro-oxidant lysosomal lipofuscin cause functional decline of the retinal pigment epithelium (RPE), which contributes to age-related macular degeneration. In mice with an RPE-specific phagocytosis defect due to lack of ?v?5 integrin receptors, RPE accumulation of lipofuscin suggests that the age-related blindness we previously described in this model may also result from oxidative stress. Cellular and molecular targets of oxidative stress in the eye remain poorly understood. Here we identify actin among 4-hydroxynonenal (HNE) adducts formed specifically in ?5?/? RPE but not neural retina with age. HNE modification directly correlated with loss of resistance of actin to detergent extraction, suggesting cytoskeletal damage in aging RPE. Dietary enrichment with natural antioxidants grapes or marigold extract containing macular pigments lutein/zeaxanthin was sufficient to prevent HNE-adduct formation, actin solubility, lipofuscin accumulation, and age-related cone and rod photoreceptor dysfunction in ?5?/? mice. Acute generation of HNE-adducts directly destabilized actin but not tubulin cytoskeletal elements of RPE cells. These findings identify destabilization of the actin cytoskeleton as a consequence of physiological, sublethal oxidative burden of RPE cells in vivo that is associated with age-related blindness and that can be prevented by consuming an antioxidant-rich diet.
Yu, Chia-Chia; Nandrot, Emeline F.; Dun, Ying; Finnemann, Silvia C.
A 32-year-old female athlete underwent arthroscopy for a second recurrence of pigmented villonodular synovitis (PVNS), which was extrasynovial, seen on magnetic resonance imaging. It was noted on arthroscopy that (1) the nodules moved medially with joint insufflation, (2) the nodules were less prominent than on magnetic resonance imaging, and (3) more than 95% of the recurrent tumor was hidden by neosynovium. We believe that the extrasynovial location is because of the more rapid proliferation of the neosynovium relative to the growth of the remaining tumor cells after the previous resection. In resecting pigmented villonodular synovitis with a high risk of recurrence, a layer of periarticular fat should be removed and the surgeon should be wary of change in position with insufflation. PMID:21889289
Jobe, Christopher M; Raza, Anwar; Zuckerman, Lee
The natural range of hair and skin colour is a continuous spectrum, controlled by multiple genes in a complex fashion. Many of these genes are as yet unknown, but several key pigmentation genes have been characterised, in particular the melanocortin 1 receptor gene (MC1R). Here, the function and known mutations of MC1R and other human pigmentation genes including ASIP, MATP, SLC24A5, TYR, TYRP1 and OCA2 are outlined, and a forensic test based on MC1R SNPs presented. The forensic utility of this and potential future genetic tests for phenotypic traits are discussed, in the light of the extensive debate on the ethics of predicting phenotypic traits from crime scene samples. PMID:19083738
of pigments and their formation reaction. In the experimental mixtures we replaced ZnO, present in the composition of wfllemite, by NiO in amounts of from 0.05 to 1 mole. The synthesis was accomplished by solid phase sintering. The salts and oxides in certain stoichiometric ratios were blended in the moist state (porcelain grinder on glass), and the resulting paste after
G. N. Maslennikova; A. I. Glebycheva; N. P. Fomina
1.The visual pigments of 27 species of crabs from a variety of habitats were investigated by microspectrophotometry of the isolated rhabdomeric photoreceptors. The rhodopsins ranged in?max from 473 to 515 nm (Tables 1 and 2). No evidence was found for the presence of more than a single rhodopsin in retinular cells 1–7.2.All rhodopsins produced thermally stable metarhodopsins on irradiation with
Thomas W. Cronin; Richard B. Forward Jr
We describe monolayer nanosheets of calcium copper tetrasilicate, CaCuSi(4)O(10), which have strong near-IR luminescence and are amenable to solution processing methods. The facile exfoliation of bulk CaCuSi(4)O(10) into nanosheets is especially surprising in view of the long history of this material as the colored component of Egyptian blue, a well-known pigment from ancient times. PMID:23215240
Johnson-McDaniel, Darrah; Barrett, Christopher A; Sharafi, Asma; Salguero, Tina T
The authors assess the corrosion resistance, crystal structure, chemical composition and color properties of a variety of zircon-based materials used as pigments and protective coatings for ceramic tiles. The constituents of these materials include, apart from zircon, iron oxides, vanadium oxides, and the sulfides, selenides and tellurides of cadmium. The effects of these constituents on the structural behavior of the zirconium silicate are investigated.
Cherepanov, E.S.; Grum-Grzhimailo, O.S.; Belostotskaya, N.S.; Bibilashvili, M.S.
Macular edema, a condition usually associated with an underlying disease process, is a common cause of severe visual loss. There have been a variety of approaches to the treatment of macular edema; within the past few years, however, intravitreal corticosteroid treatments have emerged as an increasingly used treatment option for patients with macular edema. Intravitreal delivery allows the steroid to
Matthew A. Cunningham; Jeffrey L. Edelman; Shalesh Kaushal
AIMSTo analyse the histopathology of classic and occult choroidal neovascular membrane surgical specimens in age related macular degeneration.METHODS35 membranes, from a consecutive series of surgically removed choroidal neovascular membranes in age related macular degeneration, were classified as classic or occult following the guidelines of the Macular Photocoagulation Study. Membranes with classic as well as occult components were considered as mixed
B A Lafaut; K U Bartz-Schmidt; C Vanden Broecke; S Aisenbrey; J J De Laey; K Heimann
Eight types of telangiectases were studied by light and electron microscopy and by 3-dimensional reconstruction from photomicrographs. Five were macular: mat telangiectasia of scleroderma, generalized essential telangiectasia, nevus flammeus, and 2 macular types not previously described. Three were papular: cherry angioma, angiokeratoma (Fabry), and angiokeratoma (Fordyce). The macular telangiectases were produced by dilatation of postcapillary venules of the upper horizontal
Irwin M. Braverman; Agnes Keh-Yen
Malattia Leventinese (ML) is an autosomal dominant inherited macular degeneration with a middle-age onset. Phenotypically, the disease closely resembles Age-related Macular Degeneration (AMD), a condition affecting 20% of the population over age 65 and the leading cause of blindness in the elderly in the Western world. There is no cure for macular degeneration, and the supportive treatments are limited. Patients
Nicholas W. Keiser; Daniel C. Chung; Waixing Tang; Zhanyong Wei; Albert Maguire; Jean Bennett; Jeannette L. Bennicelli
PURPOSE: To report the surgical technique, outcome, and histologic findings involving indocyanine green staining and removal of internal limiting membrane in primary macular hole surgery.METHODS: Prospectively, consecutive patients with idiopathic macular hole or myopic macular hole with retinal detachment were recruited. After pars plana vitrectomy and epiretinal membrane removal, the internal limiting membrane was stained and removed. The specimens were
Alvin K. H Kwok; Winnie W. Y Li; C. P Pang; Timothy Y. Y Lai; Gary H. F Yam; Nongnart R Chan; Dennis S. C Lam
Aging of retinal pigment epithelial (RPE) cells of the eye is marked by accumulations of bisretinoid fluorophores; two of the compounds within this lipofuscin mixture are A2E and all-trans-retinal dimer. These pigments are implicated in pathological mechanisms involved in some vision-threatening disorders including age-related macular degeneration (AMD). Studies have shown that bisretinoids are photosensitive compounds that undergo photooxidation and photodegradation when irradiated with short wavelength visible light. Utilizing ultra performance liquid chromatography (UPLC) with electrospray ionization mass spectrometry (ESI-MS) we demonstrate that photodegradation of A2E and all-trans-retinal dimer generates the dicarbonyls glyoxal (GO) and methylglyoxal (MG), that are known to modify proteins by advanced glycation endproduct (AGE) formation. By extracellular trapping with aminoguanidine, we established that these oxo-aldehydes are released from irradiated A2E-containing RPE cells. Enzyme-linked immunosorbant assays (ELISA) revealed that the substrate underlying A2E-containing RPE was AGE-modified after irradiation. This AGE deposition was suppressed by prior treatment of the cells with aminoguanidine. AGE-modification causes structural and functional impairment of proteins. In chronic diseases such as diabetes and atherosclerosis, MG and GO modify proteins by non-enzymatic glycation and oxidation reactions. AGE-modified proteins are also components of drusen, the sub-RPE deposits that confer increased risk of AMD onset. These results indicate that photodegraded RPE bisretinoid is likely to be a previously unknown source of MG and GO in the eye.
Yoon, Kee Dong; Yamamoto, Kazunori; Ueda, Keiko; Zhou, Jilin; Sparrow, Janet R.
A simple method was developed for the extraction and determination of color pigments in cochineals (Dactylopius coccus Costa). The procedure was based on the solvent extraction of pigments in insect samples using methanol:water (65:35, v:v) as extractant. Two-level factorial design was used in order to optimize the solvent extraction parameters: temperature, time, methanol concentration in the extractant mixture, and the number of extractions. The results suggest that the number of extractions is statistically the most significant factor. The separation and determination of the pigments was carried out by high-performance liquid chromatography with UV-visible detection. Because the absorption spectra of different pigments are different in the visible region, it is convenient to use a diode array detector to obtain chromatographic profiles that allow for the characterization of the extracted pigments. PMID:12428945
González, Mónica; Méndez, Jesús; Carnero, Aurelio; Lobo, M Gloria; Afonso, Ana
Degeneration and loss of retinal pigment epithelium (RPE) is the cause of a number of degenerative retinal diseases, including age-related macular degeneration (AMD), retinitis pigmentosa, and diabetic retinopathy, leading to blindness that affects three million Americans as of now. Transplantation of RPE aims to restore retinal structure and the interaction between the RPE and photoreceptors, which is fundamental to sight. Although a significant amount of progress has been made in the past 20 years in autologous RPE transplantation, sources for RPE cells are limited. Recent advances in stem cell culture and differentiation techniques have allowed the generation of RPE cells from pluripotent stem cells. In this review, we discuss strategies for generating functional RPE cells from human embryonic stem cells and induced pluripotent stem cells, and summarize transplantation studies of these derived RPEs. We conclude with challenges in cell-replacement therapies using human embryonic and induced pluripotent stem cell-derived RPEs. PMID:20528731
Uygun, Basak E; Sharma, Nripen; Yarmush, Martin
Clinical and experimental evidence supports that chronic oxidative stress is a primary contributing factor to numerous retinal degenerative diseases, such as age-related macular degeneration (AMD). Eyes obtained postmortem from AMD patients have extensive free radical damage to the proteins, lipids, DNA, and mitochondria of their retinal pigment epithelial (RPE) cells. In addition, several mouse models of chronic oxidative stress develop many of the pathological hallmarks of AMD. However, the extent to which oxidative stress is an etiologic component versus its involvement in disease progression remains a major unanswered question. Further, whether the primary target of oxidative stress and damage is photoreceptors or RPE cells, or both, is still unclear. In this review, we discuss the major functions of RPE cells with an emphasis on the oxidative challenges these cells encounter and the endogenous antioxidant mechanisms employed to neutralize the deleterious effects that such stresses can elicit if left unchecked.
Plafker, Scott M.; O'Mealey, Gary B.; Szweda, Luke I.
The introduction of optical coherence tomography has allowed accurate measurement of the size of macular holes. A retrospective consecutive review was performed of 21 patients undergoing macular hole repair with vitrectomy, gas tamponade, and autologous platelet injection and we assessed the effect of macular hole parameters on anatomic and functional outcomes. We looked at the demographic features, final visual outcome, and anatomical closure. Twenty-one patients were included in the study. They underwent routine vitrectomy with gas tamponade (C3F8) and injection of autologous platelets. All patients were advised to maintain a facedown posture for 2 weeks. Anatomical closure was confirmed in all cases and 20 out of 21 of patients had improved postoperative visual acuity by two or more lines. In our series, the macular hole dimensions did not have much effect on the final results. The use of autologous platelets and strict facedown posture seems to be the deciding factor in good anatomical and visual outcome irrespective of macular hole dimensions. PMID:23626459
Konstantinidis, Aristeidis; Hero, Mark; Nanos, Panagiotis; Panos, Georgios D
Aim Our aim is to use ultrasound to non-invasively detect differences in choroidal microarchitecture possibly related to ischaemia among normal eyes and those with wet and dry age-related macular degeneration (AMD). Design Prospective case series of subjects with dry AMD, wet AMD and age-matched controls. Methods Digitised 20?MHz B-scan radiofrequency ultrasound data of the region of the macula were segmented to extract the signal from the retina and choroid. This signal was processed by a wavelet transform, and statistical modelling was applied to the wavelet coefficients to examine differences among dry, wet and non-AMD eyes. Receiver operating characteristic (ROC) analysis was used to evaluate a multivariate classifier. Results In the 69 eyes of 52 patients, 18 did not have AMD, 23 had dry AMD and 28 had wet AMD. Multivariate models showed statistically significant differences between groups. Multiclass ROC analysis of the best model showed an excellent volume-under-curve of 0.892±0.17. The classifier is consistent with ischaemia in dry AMD. Conclusions Wavelet augmented ultrasound is sensitive to the organisational elements of choroidal microarchitecture relating to scatter and fluid tissue boundaries such as seen in ischaemia and inflammation, allowing statistically significant differentiation of dry, wet and non-AMD eyes. This study further supports the association of ischaemia with dry AMD and provides a rationale for treating dry AMD with pharmacological agents to increase choroidal perfusion. ClinicalTrials.gov registration NCT00277784.
Coleman, D Jackson; Silverman, Ronald H; Rondeau, Mark J; Lloyd, Harriet O; Khanifar, Aziz A; Chan, R V Paul
Purpose To relate costs and treatment benefits for macular edema due to diabetes (DME) and branch and central retinal vein occlusion (BRVO, CRVO). Design A model of resource utilization, outcomes, and cost effectiveness and utility. Participants none Methods Results from published clinical trials (index studies) of laser, intravitreal corticosteroids, intravitreal anti-vascular endothelial growth factor (VEGF) agents, and vitrectomy trials were used to ascertain visual benefit and clinical protocols. Calculations followed from the costs of one year of treatment for each treatment modality and the visual benefits as ascertained. Main Outcome measures Visual acuity (VA) saved, cost of therapy, cost per line saved, cost per line-year saved, and costs per quality adjusted life years (QALYs). Results The lines saved for DME (0.26 to 2.02), BRVO (0.74 to 4.92), and CRVO (1.2 to 3.75) yielded calculations of costs/line of saved VA for DME ($1329 to 11609), BRVO ($494 to 13039), and CRVO ($704 to 7611), costs/line-year for DME ($60 to 561), BRVO ($25 to 754), and CRVO ($45 to 473), and costs/QALY of $824 to $25566. Conclusion Relative costs and benefits should be considered in perspective when applying and developing treatment strategies.
Smiddy, William E.
Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations.
Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.
Age-related macular degeneration (AMD), a progressive condition that is untreatable in up to 90% of patients, is a leading cause of blindness in the elderly worldwide. The two forms of AMD, wet and dry, are classified based on the presence or absence of blood vessels that have disruptively invaded the retina, respectively. A detailed understanding of the molecular mechanisms underlying wet AMD has led to several robust FDA-approved therapies. In contrast, there are not any approved treatments for dry AMD. In this review, we provide insight into the critical effector pathways that mediate each form of disease. The interplay of immune and vascular systems for wet AMD, and the proliferating interest in hunting for gene variants to explain AMD pathogenesis, are placed in the context of the latest clinical and experimental data. Emerging models of dry AMD pathogenesis are presented, with a focus on DICER1 deficit and the toxic accumulation of retinal debris. A recurring theme that spans most aspects of AMD pathogenesis is defective immune modulation in the classically immune-privileged ocular haven. Interestingly, the latest advances in AMD research highlight common molecular disease pathways with other common neurodegenerations. Finally, the therapeutic potential of intervening at known mechanisms of AMD pathogenesis is discussed.
Ambati, Jayakrishna; Fowler, Benjamin J.
Hydroxytyrosol (HTS) is a natural polyphenol abundant in olive oil. Increasing evidence indicates HTS has beneficial effect on human health for preventing various diseases. In the present study, we investigated the protective effects of HTS on acrolein-induced toxicity in human retinal pigment epithelial cell line, ARPE-19, a cellular model of smoking- and age-related macular degeneration. Acrolein, a major component of the gas phase cigarette smoke and also a product of lipid peroxidation in vivo, at 75 ?mol/L for 24 h caused significant loss of cell viability, oxidative damage (increase in oxidant generation and oxidative damage to proteins and DNA, decrease in antioxidants and antioxidant enzymes, and also inactivation of the Keap1/Nrf2 pathway), and mitochondrial dysfunction (decrease in membrane potential, activities of mitochondrial complexes, viable mitochondria, oxygen consumption, and factors for mitochondrial biogenesis, and increase in calcium). Pre-treatment with HTS dose dependently and also time dependently protected the ARPE-19 cells from acrolein-induced oxidative damage and mitochondrial dysfunction. A short-term pre-treatment with HTS (48 h) required > 75 ?mol/L for showing protection while a long-term pre-treatment (7 days) showed protective effect from 5 ?mol/L on. The protective effect of HTS in this model was as potent as that of established mitochondria-targeting antioxidant nutrients. These results suggest that HTS is also a mitochondrial-targeting antioxidant nutrient and that dietary administration of HTS may be an effective measure in reducing and or preventing cigarette smoke-induced or age-related retinal pigment epithelial degeneration, such as age-associated macular degeneration. PMID:20938484
Liu, Zhongbo; Sun, Lijuan; Zhu, Lu; Jia, Xu; Li, Xuesen; Jia, Haiqun; Wang, Ying; Weber, Peter; Long, Jiangang; Liu, Jiankang
Purpose: To assess the natural course of the mild diabetic macular edema(DME) and to compare the visual outcomes with the patients with receiving either macular laser photocoagulation or intravitreal injection of triamcinolone acetonide(IVTA). Methods: 28 eyes with central macular thickness (CMT) of between 250 to 300µm were followed without treatment and 48 eyes with CMT between 300 to 500µm had been divided into 3 subgroups according to treatment. We evaluated the best corrected visual acuity (BCVA) and CMT of natural course group and compared the BCVA and CMT of the patients who had been treated with IVTA or macular laser treatment. Results: The eyes with DME between 250 to 300µm showed no significant change in BCVA and CMT at 6 month. Among the eyes with DME between 300 to 500µm, all 3 subgroups showed no statistically significant change of BCVA at any follow up period and no significant difference was revealed among the subgroups. All subgroups showed significant reduction of CMT after 1 month and maintained until final follow-up and there was no significant difference among subgroups. Conclusions: Mild DME between 250 to 500µm did not show significant worsening of BCVA or macular edema without any specific treatment.
Kwon, Soon Il; Baek, Sung Uk; Park, In Won
Untreatable hereditary macular dystrophy (HMD) presents a major burden to society in terms of the resulting patient disability and the cost to the healthcare provision system. HMD results in central vision loss in humans sufficiently severe for blind registration, and key issues in the development of therapeutic strategies to target these conditions are greater understanding of the causes of photoreceptor loss and the development of restorative procedures. More effective and precise analytical techniques coupled to the development of transgenic models of disease have led to a prolific growth in the identification and our understanding of the genetic mutations that underly HMD. Recent successes in driving differentiation of pluripotent cells towards specific somatic lineages have led to the development of more efficient protocols that can yield enriched populations of a desired phenotype. Retinal pigmented epithelial cells and photoreceptors derived from these are some of the most promising cells that may soon be used in the treatment of specific HMD, especially since rapid developments in the field of induced pluripotency have now set the stage for the production of patient-derived stem cells that overcome the ethical and methodological issues surrounding the use of embryonic derivatives. In this review we highlight a selection of HMD which appear suitable candidates for combinatorial restorative therapy, focusing specifically on where those photoreceptor loss occurs. This technology, along with increased genetic screening, opens up an entirely new pathway to restore vision in patients affected by HMD. PMID:19551904
Mellough, Carla B; Steel, David H W; Lako, Majlinda
Deficient expression of the RNase III DICER1, which leads to the accumulation of cytotoxic Alu RNA, has been implicated in degeneration of the retinal pigmented epithelium (RPE) in geographic atrophy (GA), a late stage of age-related macular degeneration that causes blindness in millions of people worldwide. Here we show increased extracellular-signal-regulated kinase (ERK) 1/2 phosphorylation in the RPE of human eyes with GA and that RPE degeneration in mouse eyes and in human cell culture induced by DICER1 depletion or Alu RNA exposure is mediated via ERK1/2 signaling. Alu RNA overexpression or DICER1 knockdown increases ERK1/2 phosphorylation in the RPE in mice and in human cell culture. Alu RNA-induced RPE degeneration in mice is rescued by intravitreous administration of PD98059, an inhibitor of the ERK1/2-activating kinase MEK1, but not by inhibitors of other MAP kinases such as p38 or JNK. These findings reveal a previously unrecognized function of ERK1/2 in the pathogenesis of GA and provide a mechanistic basis for evaluation of ERK1/2 inhibition in treatment of this disease.
Dridi, Sami; Hirano, Yoshio; Tarallo, Valeria; Kim, Younghee; Fowler, Benjamin J.; Ambati, Balamurali K.; Bogdanovich, Sasha; Chiodo, Vince A.; Hauswirth, William W.; Kugel, Jennifer F.; Goodrich, James A.; Ponicsan, Steven L.; Hinton, David R.; Kleinman, Mark E.; Baffi, Judit Z.; Gelfand, Bradley D.; Ambati, Jayakrishna
Geographic atrophy (GA), an untreatable advanced form of age-related macular degeneration, results from retinal pigmented epithelium (RPE) cell death. Here we show that the microRNA (miRNA)-processing enzyme DICER1 is reduced in the RPE of humans with GA, and that conditional ablation of Dicer1, but not seven other miRNA-processing enzymes, induces RPE degeneration in mice. DICER1 knockdown induces accumulation of Alu RNA in human RPE cells and Alu-like B1 and B2 RNAs in mouse RPE. Alu RNA is increased in the RPE of humans with GA, and this pathogenic RNA induces human RPE cytotoxicity and RPE degeneration in mice. Antisense oligonucleotides targeting Alu/B1/B2 RNAs prevent DICER1 depletion-induced RPE degeneration despite global miRNA downregulation. DICER1 degrades Alu RNA, and this digested Alu RNA cannot induce RPE degeneration in mice. These findings reveal a miRNA-independent cell survival function for DICER1 involving retrotransposon transcript degradation, show that Alu RNA can directly cause human pathology, and identify new targets for a major cause of blindness.
Kaneko, Hiroki; Dridi, Sami; Tarallo, Valeria; Gelfand, Bradley D.; Fowler, Benjamin J.; Cho, Won Gil; Kleinman, Mark E.; Ponicsan, Steven L.; Hauswirth, William W.; Chiodo, Vince A.; Kariko, Katalin; Yoo, Jae Wook; Lee, Dong-ki; Hadziahmetovic, Majda; Song, Ying; Misra, Smita; Chaudhuri, Gautam; Buaas, Frank W.; Braun, Robert E.; Hinton, David R.; Zhang, Qing; Grossniklaus, Hans E.; Provis, Jan M.; Madigan, Michele C.; Milam, Ann H.; Justice, Nikki L.; Albuquerque, Romulo J.C.; Blandford, Alexander D.; Bogdanovich, Sasha; Hirano, Yoshio; Witta, Jassir; Fuchs, Elaine; Littman, Dan R.; Ambati, Balamurali K.; Rudin, Charles M.; Chong, Mark M.W.; Provost, Patrick; Kugel, Jennifer F.; Goodrich, James A.; Dunaief, Joshua L.; Baffi, Judit Z.; Ambati, Jayakrishna
Aims To describe subretinal debris found on ultrastructural examination in an eye with macular telangiectasia (MacTel) type 2 and on optical coherence tomography (OCT) in a subset of patients with MacTel type 2. Methods Blocks from the mid-periphery and temporal perifovea of an eye with clinically documented MacTel type 2 were examined with electron microscopy (EM). Cases came from the Sydney centre of the MacTel project and the practices of the authors. Results On EM examination, subretinal debris was found in the perifovea with accumulation of degenerate photoreceptor elements in the subretinal space. Despite the substantial subretinal debris, there was minimal retinal pigment epithelial (RPE) reaction. Focal defects were seen in the inner limiting membrane in the perifovea. Of the 65 Sydney MacTel project participants, three (5%) had prominent yellow material at the fovea. OCT revealed smooth mounds between the RPE and the ellipsoid region. The material was hyperautofluorescent. Conclusions This study suggests that subretinal accumulation of photoreceptor debris may be a feature of MacTel type 2. Ultrastructural and OCT evidence of disease beyond the vasculature, involving photoreceptors and Muller cells, is presented.
Cherepanoff, Svetlana; Killingsworth, Murray C; Zhu, Meidong; Nolan, Timothy; Hunyor, Alex P; Young, Stephanie H; Hageman, Gregory S; Gillies, Mark C
The largest risk factor for age-related macular degeneration (ARMD) is advanced age. With aging, there is a striking accumulation of neutral lipids in Bruch's membrane (BrM) of normal eye that continues through adulthood. This accumulation has the potential to significantly impact the physiology of the retinal pigment epithelium (RPE). It also ultimately leads to the creation of a lipid wall at the same locations where drusen and basal linear deposit, the pathognomonic extracellular, lipid-containing lesions of ARMD, subsequently form. Here, we summarize evidence obtained from light microscopy, ultrastructural studies, lipid histochemistry, assay of isolated lipoproteins, and gene expression analysis. These studies suggest that lipid deposition in BrM is at least partially due to accumulation of esterified cholesterol-rich, apolipoprotein B-containing lipoprotein particles produced by the RPE. Furthermore, we suggest that the formation of ARMD lesions and their aftermath may be a pathological response to the retention of a sub-endothelial apolipoprotein B lipoprotein, similar to a widely accepted model of atherosclerotic coronary artery disease (Tabas, I., K. J. Williams, and J. Borén. 2007. Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therapeutic implications. Circulation. 116:1832–1844). This view provides a conceptual basis for the development of novel treatments that may benefit ARMD patients in the future.
Curcio, Christine A.; Johnson, Mark; Huang, Jiahn-Dar; Rudolf, Martin
Despite the fact that the retina is a fairly accessible portion of the central nervous system, there are virtually no treatments for early age-related macular degeneration (AMD). AMD is a degenerative retinal disease that causes progressive loss of central vision and is the leading cause of irreversible vision loss and legal blindness in individuals over the age of 50. Both environmental and genetic components play a role in its development. AMD is a multifactorial disease with characteristics that include drusen, hyperpigmentation and/or hypopigmentation of the retinal pigment epithelium (RPE), geographic atrophy and, in a subset of patients, late-stage choroidal neovascularization (CNV). Drugs that inhibit vascular endothelial growth factor (VEGF) have proven effective in treating late-stage CNV, but optimal means of drug delivery remains to be determined. Microscopic particles, whose size is on the nanometer scale, show considerable promise for drug delivery to the retina, for gene therapy, and for powering prosthetic “artificial retinas.” This article summarizes the pathophysiology of AMD stressing potential applications from nanotechnology.
Birch, David G; Liang, Fong Qi
From the retina of the land-locked population of the sea lamprey, Petromyzon marinus, a photolabile pigment was extracted which was identified spectrophotometrically as a member of the rhodopsin group of pigments. Using the absorption spectrum of a relatively pure solution and analysis by means of difference spectra, the peak of this pigment was placed at about 497 mµ. The method of selective bleaching by light of different wave lengths revealed no significant amounts of any other pigment in the extracts. A similar pigment was also detected in retinal extracts of the Pacific Coast lamprey, Entospenus tridentatus. These results are significant for two reasons: (a) the lamprey is shown to be an example of an animal which spawns in fresh water but which is characterized by the presence of rhodopsin, rather than porphyropsin, in the retina; (b) the primitive phylogenetic position of the lamprey suggests that rhodopsin was the visual pigment of the original vertebrates.
Removal of internal limiting membranes (ILMs) is a potentially useful surgical approach to close an idiopathic macular hole. However, the removal of ILMs is difficult to perform because of poor visibility of the ILMs. We have developed a technique for staining the ILM with a solution of indocyanine green to facilitate the removal of ILMs in eyes with an idiopathic macular hole. Thirteen eyes of 13 patients (8 women and 5 men, aged from 54 to 68 years) with idiopathical macular hole stage 3 or stage 4 that underwent removal of ILMs using this technique had an anatomical closure rate of 92% and an improvement of visual acuity of 89% (>/=2 Snellen letter chart lines). The excised specimens were evaluated using transmission electron microscopy. Our results show that this technique is safe and useful in visualizing the ILM, leading to the performance of successful removal of an ILM with least damage to the retina. Arch Ophthalmol. 2000;118:1116-1118 PMID:10922208
Kadonosono, K; Itoh, N; Uchio, E; Nakamura, S; Ohno, S
A 13-year-old boy was referred because of visual deterioration in his right eye. The visual acuity was two meters of counting fingers. Indirect ophthalmoscopy and biomicroscopy revealed exudative macular edema as well as tumor-like telangiectatic vessels and exudation in temporal periphery. With diagnosis of Coats' disease (stage II) confirmed by fluorescein angiography, three intravitreal injections of bevacizumab were performed at 6-week intervals. One year after the last injection, there was a significant resolution of macular edema as well as visual acuity improvement to 20/20. This is the first case report in which a distinct improvement in macular edema was observed with intravitreal bevacizumab in Coats' disease.
Entezari, Morteza; Ramezani, Alireza; Safavizadeh, Ladan; Bassirnia, Nader
A 13-year-old boy was referred because of visual deterioration in his right eye. The visual acuity was two meters of counting fingers. Indirect ophthalmoscopy and biomicroscopy revealed exudative macular edema as well as tumor-like telangiectatic vessels and exudation in temporal periphery. With diagnosis of Coats' disease (stage II) confirmed by fluorescein angiography, three intravitreal injections of bevacizumab were performed at 6-week intervals. One year after the last injection, there was a significant resolution of macular edema as well as visual acuity improvement to 20/20. This is the first case report in which a distinct improvement in macular edema was observed with intravitreal bevacizumab in Coats' disease. PMID:20029156
Entezari, Morteza; Ramezani, Alireza; Safavizadeh, Ladan; Bassirnia, Nader
Purpose Cannabinoid receptors have been detected in neuron cells and proposed as potential therapeutic agents in neurodegenerative disorders because of their involvement in controlling neural cell survival and death. However, their presence and role in human retinal pigment epithelial (RPE) cells, which play a key role in initiating and developing age related macular degeneration (ARMD), have never been investigated. Here we analyzed the expression of and changes in cannabinoid receptors (CB1 and CB2) and one enzyme responsible for endocannabinoid hydrolysis, fatty acid amide hydrolase (FAAH), in RPE cell oxidative damage process, a cellular model of ARMD. Methods Primary human RPE cells and cells from the ARPE-19 cell line were cultured and exposed to H2O2 for 24 h to induce oxidative damage. Real time RT–PCR, immunofluorescent staining, and western blot methods were performed to study the expression of and changes in CB1 and CB2 receptors, and FAAH. Cell viability and reactive oxygen species (ROS) production were measured by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and a dichlorofluorescein (DCF) assay, respectively. PI3K/Akt and ERK1/2 protein expression and activation of signaling molecules were assessed by western blot analysis. Results By using real time RT–PCR, immunofluorescent staining and western blot methods, we showed that human RPE cells express CB1, CB2, and FAAH. Meanwhile, oxidative stress can upregulate CB1 and CB2 receptor expression, and downregulate FAAH expression. The CB1/CB2 receptor agonist, CP55,940, and the CB2 receptor agonist, JWH015 significantly protected RPE cells from oxidative damage. In addition, CP55,940 significantly reduced the levels of intracellular ROS, strengthened oxidative stress-induced activation of PI3K/Akt and reduced activation of the ERK1/2 signal pathway. Conclusions The results demonstrate the expression and regulation of CB1 and CB2 receptors and FAAH in human RPE cells. The modulation of cannabinoid receptor tone warrants consideration for future therapeutic strategies of ARMD.
Wei, Yan; Wang, Xu
FROM the hair of red mongrel dogs and New Zealand red rabbits we have extracted iron pigments which in most respects are similar to the pigments isolated before from red human hair (trichosiderin)1-3 and Rhode Island Red chicken feathers (feather siderin)3,4. These findings suggest that iron compounds play a central part in certain types of red pigmentation. To facilitate studies
Pigmented villonodular synovitis is rare in the younger child. Polyarticular involvement in this condition, regardless of patient age, is distinctly uncommon. The authors describe a case of pigmented villonodular synovitis involving multiple joints in a young boy who also had congenital anomalies of the genitourinary tract. Although rare, pigmented villonodular synovitis should be considered in the differential diagnosis of multiple joint swellings in children with congenital anomalies. PMID:9553554
Vedantam, R; Strecker, W B; Schoenecker, P L; Salinas-Madrigal, L
We report a 29-year-old white female with conjunctival pigmentation after a Stevens–Johnson syndrome (SJS) episode triggered\\u000a by sulfasalazine. The patient developed bilateral tarsal and forniceal conjunctiva and black pigmentation. Diagnostic biopsy\\u000a showed stromal monocyte infiltration consistent with chronic phase SJS and conjunctival pigment of melanic origin and not\\u000a due to drug deposition. Treatment with topical steroids and unpreserved artificial tears
Graciana Fuentes-Páez; Maria C. Mendez; Javier Montańez; Jose M. Herreras; Maria A. Saornil; Margarita Calonge
Eggshell pigment constituents were determined by a high-performance liquid chromatography method. Most of the work was done on whole clutches of red-backed shrike (Lanius collurio). In addition to the known pigments (protoporphyrin IX, biliverdin), a new pigment, zinc-containing protoporphyrin IX, was found as well. Its content was highly variable—from 0% to 100%. The content of total protoporphyrin IX (with and
I. Mikšík; V. Holá?; Z. Deyl
The authors report the formation of hard exudates and macular scarring after laser photocoagulation therapy in patients with retinopathy of prematurity (ROP). Two premature neonates, the first born at 24 weeks and the second at 25 weeks gestational age, were diagnosed as having ROP that necessitated laser photocoagulation treatment at 32 and 36 weeks, respectively. Subretinal fluid and macular hard exudation developed in both patients that eventually caused bilateral macular scarring. Subretinal macular fluid with hard exudation could lead to macular scar formation in neonates with ROP after laser photocoagulation that could significantly affect the visual prognosis in preterm infants. PMID:23819953
Epstein, Ilan J; Aziz, Hassan A; Young, Ryan C; Berrocal, Audina M
Background Progressive macular hypomelanosis is characterized by ill-defined, non-scaly, hypopigmented macules primarily on the trunk of the body. Although numerous cases of progressive macular hypomelanosis have been reported, there have been no clinicopathologic studies of progressive macular hypomelanosis in Korean patients. Objective In this study we examined the clinical characteristics, histologic findings, and treatment methods for progressive macular hypomelanosis in a Korean population. Methods Between 1996 and 2005, 20 patients presented to the Department of Dermatology at Busan Paik Hospital with acquired, non-scaly, confluent, hypopigmented macules on the trunk, and with no history of inflammation or infection. The medical records, clinical photographs, and pathologic findings for each patient were examined. Results The patients included 5 men and 15 women. The mean age of onset was 21.05±3.47 years. The back was the most common site of involvement. All KOH examinations were negative. A Wood's lamp examination showed hypopigmented lesions compared with the adjacent normal skin. A microscopic examination showed a reduction in the number of melanin granules in the lesions compared with the adjacent normal skin, although S-100 immunohistochemical staining did not reveal significant differences in the number of melanocytes. Among the 20 patients, 7 received topical drug therapy, 6 were treated with narrow-band ultraviolet B phototherapy, 4 received oral minocycline, and 3 did not receive any treatment. Conclusion Most of the patients with progressive macular hypomelanosis had asymptomatic ill-defined, non-scaly, and symmetric hypopigmented macules, especially on the back and abdomen. Histologically, the number of melanocytes did not differ significantly between the hypopigmented macules and the normal perilesional skin. No effective treatment is known for progressive macular hypomelanosis; however, narrow-band ultraviolet B phototherapy may be a useful treatment modality.
Hwang, Seon Wook; Hong, Soon Kwon; Kim, Sang Hyun; Park, Jeong Hoon; Seo, Jong Keun; Sung, Ho Suk
We reported the case of a 92-year-old woman with a pigmented and non-pigmented surface of the pedunculated nodule on her lower leg. Microscopic examination revealed that this nodule consisted of a component of small, dark, homogenous, poroid cells and cuticular cells in the dermis. The histopathological features of the lesion were consistent with poroid neoplasm. Immunohistochemistry showed that HMB-45 and Melan-A were positive in malanocytes and melanophages of the pigmented areas. Unlike most poroid neoplasms, this case showed pigmented lesion mimicked nodular melanoma. PMID:20536669
Mitsuishi, Tsuyoshi; Ansai, Shin-ichi; Ueno, Takashi; Kawana, Seiji
Pigmented lymph nodes are traditionally associated with melanoma and metastatic malignancy. This report describes the case of 22-year-old white man, who presented with painful right groin lymphadenopathy. Groin ultrasound and computed tomography confirmed an enlarged (2 cm) right inguinal lymph node. Elective excision of this lymph node was conducted due to unresolving pain, and a pigmented node was retrieved. Although a suspicious finding, histologic examination demonstrated black pigment infiltration from a decorative tattoo on the right leg. Unresolving, painful, pigmented lymphadenopathy can result from decorative tattooing. Selective excision of the affected lymph node and histologic examination result in symptom resolution and can aide in appropriate diagnosis. PMID:23680325
Balasubramanian, Ishwarya; Burke, John P; Condon, Eoghan
Purpose To report the first described cases of peripheral yellow corneal rings secondary to vitamin supplementation for age-related macular degeneration (ARMD). Design Retrospective single-center case series. Participants The eyes of four patients taking vitamin supplementation for ARMD were examined at University of Pittsburgh Medical Center (UPMC) Department of Ophthalmology between January 2010 and April 2011. Methods We reviewed the medical records of four patients with peripheral corneal rings receiving vitamin supplementation for ARMD. Main Outcome Measures the presence of peripheral yellow corneal rings, skin findings, and serum carotene levels. Results Each patient had circumferential yellow peripheral corneal rings and exhibited subtle yellowing of the skin most notable on the palms. Serum carotene levels were normal in two of the three cases and markedly elevated in the last case in which it was measured. Conclusion It is unclear at this time how to counsel patients with this ocular finding. We suspect that these rings are more common than generally appreciated as they can have a subtle appearance or may be misdiagnosed as arcus senilis. We suggest that a formal study be performed on a cohort of patients taking macular degeneration vitamin supplementation that specifically screens for yellow rings and measures serum carotene levels when they are identified.
Eller, Andrew W; Gorovoy, Ian R; Mayercik, Vera A
Purpose To assess ocular hemodynamic response to intravitreal triamcinolone in patients with macular edema due to diabetes or retinal\\u000a vein occlusion.\\u000a \\u000a \\u000a \\u000a Methods Forty-three patients that were injected by intravitreal triamcinolone acetonide (0.1 cc 4 mg) for unilateral macular edema\\u000a due to diabetes mellitus (n = 17) and occlusion of retinal vein (n = 26) underwent ocular hemodynamic evaluation by color Doppler imaging (CDI) before and one, two and
Osman Çekiç; Yavuz Bardak; ?ahin U. T??; Aykut Demirkol; Mustafa M. Ekim; Önem Alt?nta?; Ahmet Ye?ilda?; Orhan Oyar
We encountered a patient with cystoid macular edema (CME) secondary to paclitaxel use. A 57-year-old man presented with gradual decreased bilateral vision. His chemotherapeutic regimen consisted of bevacizumab, paclitaxel (175 mg/m2 for 5 months), and carboplatin. Optical coherence tomography imaging revealed bilateral CME greater than 500 µm. However, one year later, visual acuity was improved, best-corrected Snellen visual acuity was 40 / 80 in each eye, and CME was spontaneously improved. Our study confirmed that macular edema associated with paclitaxel use shows spontaneous resolution and improvement of visual acuity after a change of chemotherapeutic regimen.
Ham, Dong Sik; Lee, Joo Eun; Yun, Il Han
A 57-year-old woman was treated by photodynamic therapy for macular edema due to idiopathic juxtafoveal telangiectasis (presumed type 1A) without subretinal neovascularization. Initial visual acuity of the treated eye was 20/200 and it improved to 20/40 by 3 months after the photodynamic therapy session. Visual acuity remained stable 32 months after the treatment. Color photographs and fundus fluorescein angiography before and after photodynamic therapy revealed regression of hemorrhages, exudates, and fluorescein leakage. Photodynamic therapy has long-term benefits for the patient with idiopathic juxtafoveal telangiectasis, presumed type 1A, because it can improve visual acuity and macular edema. PMID:19205501
Kotoula, Maria G; Chatzoulis, Dimitrios Z; Karabatsas, Constantinos H; Tsiloulis, Aristoteles; Tsironi, Evangelia E
Macular amyloidosis is a common problem seen dermatology out-patient department. Generalized macular amyloidosis presenting with a poikilodermatous appearance is rare. In our case, an 18-year-old male presented with generalized hypopigmented macules with a poikilodermatous appearance of 10-year duration. His developmental milestones were normal with negative family history of similar complaints. Histopathology of hyperpigmented lesions revealed hyperkeratosis and acanthosis of epidermis and hypopigmented lesion showing only hyperkeratosis. Both lesions were showing the deposition of amorphous, hazy material in the tips of papillary dermis with perivascular inflammatory infiltrate. Congo red staining of the amorphous material was positive for amyloid.
Kudur, Mohan H; B, Sathish Pai; H, Sripathi; Prabhu, Smitha
RationaleThe MARAN (Macular Relocation in Age-related Neovascular disease) trial was planned to assess the effectiveness of full macular relocation (MR) in patients with neovascular age-related macular degeneration (AMD).DesignRandomised, prospective, controlled clinical trial.MethodsPatients suffering from visual loss because of AMD were randomised to either surgery or a control group receiving standard treatment (observation or photodynamic therapy (PDT)). The primary end point
A M Joussen; D Wong; P Walter; B Kirchhof; J Dreyhaupt; C Bauer; J Munzinger; K Unnebrink; A Freiberger; M Seibert-Grafe; N Victor
Amiodarone is one of the most commonly used drugs for treatment of cardiac arrhythmia. Several undesirable effects are associated with its long-term use. This report describes the case of a 71-year-old female patient, with a diagnosis of cardiac arrhythmia, who presented with a stigmatizing blue-gray facial pigmentation and altered serum values of thyroid hormones associated with the intake of amiodarone. The patient was referred to her cardiologist. The aim of this report is to increase clinicians' awareness about the potential adverse effects of this drug. PMID:23823354
Gonzalez-Arriagada, Wilfredo Alejandro; Silva, Alan Roger Santos; Vargas, Pablo Agustin; Almeida, Oslei Paes de; Lopes, Marcio Ajudarte
Substitution of zinc chromate or zinc yellow, traditionally used as anticorrosive pigment, for other phosphate-based pigments that are not hazardous to health and have the same anticorrosive behaviour or even better, is studied in this paper. Four alkyd paints were specially prepared; two of them contained calcium acid phosphate or micronised zinc phosphate as anticorrosive pigments respectively. A paint containing
L. S. Hernández; B. del Amo; R. Romagnoli
Purpose. One of the most prominent changes that occurs in the retinal pigment epithelium during senescence is the progressive accumulation of the autofluorescent pigment lipofuscin. Experiments were conducted to evaluate the role of nonenzymatic oxidation of photoreceptor outer segments in retinal pigment epithelium lipofuscin formation. Methods. Albino Fischer rats were given intravitreal injections of ferrous sulfate, a catalyst that promotes
Martin L. Katz; Holly J. Stientjes; Chun-Lan Gao; J. Scott Christianson
We present the case of a 48-year-old woman with a clinically and histopathologically confirmed Kearns-Sayre syndrome who developed a maculopathy resembling an adult-onset vitelliform macular dystrophy in her right eye. DNA analysis identified the presence of multiple deletions in the mtDNA of the muscle sample, with the common deletion of 4977 bp the most abundant. To the best of our knowledge, there have been no previous reports of such macular lesion occurring in association with Kearns-Sayre syndrome. PMID:20497429
Ascaso, Francisco J; Lopez-Gallardo, Ester; Del Prado, Eduardo; Ruiz-Pesini, Eduardo; Montoya, Julio
Squamous cell carcinoma (SCC) usually lacks melanocytes within the tumor. A few reports have documented invasive SCC or SCC in situ (intraepithelial neoplasia, IEN) with melanocytic hyperplasia within the tumor, referred to as pigmented SCC, in some organs. However, case series of pigmented SCC or IEN of the esophagus have not yet been reported. This is the first study to analyze the incidence and clinicopathological features of pigmented SCC or IEN of the esophagus. We reviewed 18 surgically-resected and 122 endoscopically-resected esophageal specimens, including 79 cases of IEN. Three cases of pigmented IEN were observed in this series, and all of them were located in the middle to lower third of the esophagus. Two of 3 cases had melanocytosis in the non-neoplastic squamous epithelium around the IEN. The incidence of pigmented IEN was 2.5% of all endoscopically resected specimens and 3.8% of IEN cases. No pigmented invasive SCC was detected in both endoscopically-resected and surgically-resected specimens. The mechanism of pigmentation of esophageal IEN is unknown. However, production of melanocyte chemotactic factors by tumor cells has been demonstrated in pigmented SCC of the oral mucosa. Moreover, two of 3 cases of pigmented IEN in the present series had melanocytosis in the non-neoplastic squamous epithelium, and melanocytosis is thought to be associated with chronic esophagitis, therefore, it has been hypothesized that various stimuli can cause pigmentation in squamous epithelium. Additional studies are needed to clarify the mechanism of pigmentation in squamous IEN of the esophagus.
Ishida, Mitsuaki; Mochizuki, Yosuke; Iwai, Muneo; Yoshida, Keiko; Kagotani, Akiko; Okabe, Hidetoshi
The aim of this study was to evaluate macular ganglion cell complex (GCC) characteristics and peripapillary retinal nerve fiber layer (RNFL) thickness in patients with multiple sclerosis (MS) and to investigate the associations between these parameters and clinical characteristics of patients for evaluation perspectives of using this method for monitoring of disability and neurodegenerative processes. We examined a total of 113 participants (analysis of 211 eyes), divided into three groups: 1. 48 MS patients (66 eyes) with a history of optic neuritis (ON); 2. 35 MS patients (70 eyes) without a history of ON; 3. 30 disease-free control subjects (45 eyes). The estudy included anamnesis collection, neurological examination with assessment of EDSS scores. Refracted visual acuity prior to optical coherence tomography (OCT) was tested. RTVue-100 ??? system was used to assess peripapillary RNFL thickness and macular inner parameter (protocol GCC). The strongly correlated decline of the most RNFL and GCC indices was characteristic of all groups of MS patients with and without ON compared to controls. The damage of GCC was greater in patients with ON. The inverse correlation was found between the indices studied and the level of patient's disability. The study of GCC and RNFL thickness can be used to describe and characterize the level of axonal damage in MS and for objectification of neurodegenerative process in studies on neuroprotection and neuroreparation. PMID:22677679
Davydovskaia, M V; Tsysar', M A; Bo?ko, A N; Akopian, V S; Semenova, N S; Filonenko, I V; Fomin, A V; Gusev, E I
The macular neuroepithelium is morphologically organized as a weighted neural network for parallel distributed processing of information. The network is continuous across the striola, where some type II hair cells synapse with calyces containing type I cells with tufts of opposite directional polarities. Whether other hair cell to calyx appositions that lack synapses interact because of intercellular potassium accumulation remains an open question. A functionally important inference of macular organization is that just as arrays of hair cells communicate an entire piece of information to a nerve fiber, so do macular subarrays of nerve fibers (not single units) carry the whole coded message to the brain stem. Moreover, the size of the network subarray can expand or become more limited depending upon the strength and/or duration of the input. It is the functioning of the network and its subarrays that must be understood if we are to learn how maculas carry out their work and adapt to new environments. Simulations of functioning maculas, or subparts, based on precise morphology and known physiology are useful tools to gain insights into macular information processing. The current simulations of afferent collateral electrical activity are a prelude to development of a 3-D model. The simulations demonstrate a relationship between geometry and function, with the diameter of the stem apparently being a major determinant of electrical activity transmitted to the base in the case of collaterals with short stems. Thus, while changes in synaptic number and/or size may be an important adaptive mechanism in an altered g environment, changes in diameter of the stem is another means of altering outflow. Research on the effects of microgravity should be extremely useful in examining the validity of this and other concepts of neural adaptation, since maculas are biological linear accelerometers ideally suited to the task. Maculas are also extremely interesting to study in detail because of the richness of connectivities and submicroscopic organization they present. Many of their features are common with more complex parts of the brain. It seems possible that knowledge of the three-dimensional geometric relationships operative in a functioning macula will contribute much to the understanding of the dynamics underlying more complex behavior. Computerized approaches greatly facilitate this task and provide an objective method of analysis. It is likely that, in the end, simple rules will be found to govern optimal neural architectural organization, even at higher cognitive levels. The architecture only appears complex because we do not yet grasp its meaning.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1350896
Ross, M D; Chimento, T; Doshay, D; Cheng, R
Lower vertebrates can detect UV light with the pineal complex independently of eyes. Electrophysiological studies, together with chromophore extraction analysis, have suggested that the underlying pigment in the lamprey pineal exhibits a bistable nature, that is, reversible photoreaction by UV and visible light, which is never achieved by known UV pigments. Here we addressed the molecular identification of the pineal
Mitsumasa Koyanagi; Emi Kawano; Yoshimi Kinugawa; Tadashi Oishi; Yoshinori Shichida; Satoshi Tamotsu; Akihisa Terakita
Background information, list of materials needed, procedures used, and discussion of typical results are provided for an experiment on the thin layer chromatography of chlorophyll pigments. The experiment works well in high school, since the chemicals used are the same as those used in paper chromatography of plant pigments. (JN)
The objective of this research program was to compile a data base covering all the commercially significant dyes and pigments produced or imported in the United States. The Organic Dyes and Pigments Data Base (ODPDB) contains the following data elements: chemical-related data (co...
The means by which Nature produces her great variety of colors in the plant kingdom are fairly simple in principle. They involve only a few pigments, and other contributing factors are the structure of the colored organs and the distribution of the pigments within the tissues. The nature of the colors is substantially different, moreover, from that of colors displayed
The dynamics of pigment concentrations are diagnostic of a range of plant physiological properties and pro- cesses. This paper appraises the developing technolo- gies and analytical methods for quantifying pigments non-destructively and repeatedly across a range of spatial scales using hyperspectral remote sensing. Progress in deriving predictive relationships between various characteristics and transforms of hyperspectral reflectance data are evaluated and
George Alan Blackburn
PLANT pigments are compounds which are not volatile at the temperatures normally used in gas chromatography (up to about 250° C). The only reported, work in this field has been carried out using the methyl esters of flavonoid compounds1. In this work characterization of the pigments was attempted by the technique of analysis of the products of pyrolysis. The original
K. J. Harkiss
|Background information, list of materials needed, procedures used, and discussion of typical results are provided for an experiment on the thin layer chromatography of chlorophyll pigments. The experiment works well in high school, since the chemicals used are the same as those used in paper chromatography of plant pigments. (JN)|
Pigmented lesions of the oral cavity are of multiple origin. They can be subdivided as follows: non tumoral pigmentations, non melanin pigmented tumors or tumor-like lesions, benign melanin pigmented tumors and malignant melanomas. Among non tumoral pigmented lesions, some of them show melanin deposits: they can be associated with a systemic disease (Peutz Jeghers syndrome, Addison's disease) or have a medicamentous origin, or belong to a lichen migricans. Non tumoral and non melanin pigmentations are principally due to a heavy metal accumulation or an accidental tatoo arising after tooth treatment. Peripheral giant cell granuloma, so-called giant cell epulis is the major non pigmented non melanin pseudotumoral lesion; pigmentation is due to hemosiderin deposits. In the oral cavity nevi are principally of the intramucosal type. Blue nevus, the second type in frequency, is usually located on the hard palate. Primary malignant melanomas are rare in the oral cavity, but it is--because its very bad prognosis--the most important lesion. In order to improve the survival it is necessary to do the diagnosis as early as possible. PMID:3833244
Brocheriou, C; Kuffer, R; Verola, O
As researchers and clinicians are beginning to understand that wet age-related macular degeneration (AMD) is more than simply a vascular disease that includes angiogenic, vascular and inflammatory components, they are exploring new agents with different mechanisms of action addressing multiple targets in this complex pathophysiology. Some of them are already available in human trials or even approved vascular epithelial growth
Zhang Ni; Peng Hui
Ranibizumab (Lucentis®), a recombinant humanized IgG(1) ? isotype monoclonal antibody fragment, is approved in the US for the treatment of macular oedema following retinal vein occlusion (RVO). It binds to the receptor-binding site of active forms of vascular endothelial growth factor-A, inhibiting its biological activity. In two large, well designed, phase III trials in patients with macular oedema following branch RVO (BRVO) or central RVO (CRVO), monthly intravitreal injections of ranibizumab 0.5 mg were associated with significantly greater improvement from baseline in mean best-corrected visual acuity letter score (measured on the Early Treatment Diabetic Retinopathy Study chart) in the study eye at 6 months (primary endpoint) than sham injections. Moreover, ranibizumab was significantly more effective than sham injections with regard to improvements in central foveal thickness at 6 months, as well as several other visual acuity measures. Ranibizumab was generally well tolerated in patients with macular oedema following CRVO or BRVO. Overall, the most common adverse events with ranibizumab were consistent with the adverse event profile previously reported in patients with age-related macular degeneration. PMID:21395358
Garnock-Jones, Karly P
Stargardt disease (STGD) and late-onset fundus flavimaculatus (FFM) are autosomal recessive conditions leading to macular degenerations in childhood and adulthood, respectively. Recently, mutations of the photoreceptor cell-specific ATP binding transporter gene (ABCR) have been reported in Stargardt disease. Here, we report on the screening of the whole coding sequence of the ABCR gene in 40 unrelated STGD and 15 FFM
Jean-Michel Rozet; Sylvie Gerber; Eric Souied; Isabelle Perrault; Sophie Châtelin; Imad Ghazi; Corinne Leowski; Jean-Louis Dufier; Arnold Munnich; Josseline Kaplan; J-M Rozet