The Project MACULA Retinal Pigment Epithelium Grading System for Histology and Optical Coherence Tomography in Age-Related Macular Degeneration

Zanzottera, Emma C.; Messinger, Jeffrey D.; Ach, Thomas; Rjh, Smith; Freund, K. Bailey; Curcio, Christine A.

doi:10.1167/iovs.15-16431

Cited by 130 publications

(199 citation statements)

References 139 publications

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“…We observed that the areas with the greatest photoreceptor disorganization were often associated with multilayered or atrophied RPE ( Fig. 1 F and H), histological abnormalities that are also hallmarks of human dry AMD (26). HG retinas showed multiple additional AMDf, including subretinal deposits and RPE vacuolation, hypopigmentation, thinning, and disorganization ( Figs Hallmarks of younger, healthy RPE were similar and more frequent in LG and HGxoLG RPE, including well-maintained basal infoldings with aligned mitochondria and typical numbers of pigment granules ( Fig.…”

Section: Resultsmentioning

confidence: 76%

Involvement of a gut–retina axis in protection against dietary glycemia-induced age-related macular degeneration

Rowan

Jiang

Korem

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

190

192

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Age-related macular degeneration (AMD) is the major cause of blindness in developed nations. AMD is characterized by retinal pigmented epithelial (RPE) cell dysfunction and loss of photoreceptor cells. Epidemiologic studies indicate important contributions of dietary patterns to the risk for AMD, but the mechanisms relating diet to disease remain unclear. Here we investigate the effect on AMD of isocaloric diets that differ only in the type of dietary carbohydrate in a wild-type aged-mouse model. The consumption of a high-glycemia (HG) diet resulted in many AMD features (AMDf), including RPE hypopigmentation and atrophy, lipofuscin accumulation, and photoreceptor degeneration, whereas consumption of the lower-glycemia (LG) diet did not. Critically, switching from the HG to the LG diet late in life arrested or reversed AMDf.LG diets limited the accumulation of advanced glycation end products, long-chain polyunsaturated lipids, and their peroxidation end-products and increased C3-carnitine in retina, plasma, or urine. Untargeted metabolomics revealed microbial cometabolites, particularly serotonin, as protective against AMDf. Gut microbiota were responsive to diet, and we identified microbiota in the Clostridiales order as being associated with AMDf and the HG diet, whereas protection from AMDf was associated with the Bacteroidales order and the LG diet. Network analysis revealed a nexus of metabolites and microbiota that appear to act within a gut-retina axis to protect against diet-and age-induced AMDf. The findings indicate a functional interaction between dietary carbohydrates, the metabolome, including microbial cometabolites, and AMDf. Our studies suggest a simple dietary intervention that may be useful in patients to arrest AMD.age-related macular degeneration | glycemic index | advanced glycation end-product | gut microbiome | metabolomics A ge-related macular degeneration (AMD) is the leading cause of irremediable blindness in the industrialized world, with 200 million cases projected by 2020, at a cost of $300 billion (1, 2). Dry AMD accounts for the great majority of cases and is associated with photoreceptor cell loss, often preceded by compromise to the retina pigment epithelium (RPE) cells that nourish and remove waste from the photoreceptors. The etiology of AMD remains an enigma but is clearly multifactorial. Stresses associated with AMD include environment, age, and genetics (3). Frustratingly, there are no early biomarkers to anticipate AMD, and there are no therapies or cure.Recently, we and others observed in epidemiologic studies that, in addition to micronutrients (4-6), macronutrient quality [e.g., consuming a diet with a high glycemic index (GI)] is a significant risk factor for AMD onset and/or progress in nondiabetic humans (7)(8)(9). The GI appears to be an attractive dietary intervention target, because simple replacement of small amounts of high-index foods (such as white bread) with lower-index foods (such as wholegrain bread) can significantly reduce glycemic peaks without requiring ...

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Section: Resultsmentioning

confidence: 76%

Involvement of a gut–retina axis in protection against dietary glycemia-induced age-related macular degeneration

Rowan

Jiang

Korem

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

190

192

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“…As they occur in regions of GA, where no RPE is expected, it has been suggested that the hyperrelective material is not derived from lipofuscin or retinoid components. Recent work however has questioned if regions of GA really represent cell deserts, as patchy preservation of both the RPE and neurosensory retina has been observed (Zanzottera et al, 2015).…”

mentioning

confidence: 99%

Differentiating drusen: Drusen and drusen-like appearances associated with ageing, age-related macular degeneration, inherited eye disease and other pathological processes

Khan

Mahroo

Khan

et al. 2016

Progress in Retinal and Eye Research

172

159

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Drusen are discussed frequently in the context of their association with age-related macular degeneration (AMD). Some types may, however, be regarded as a normal consequence of ageing; others may be observed in young age groups. They also occur in a number of inherited disorders and some systemic conditions. Whilst drusen are classically located external (sclerad) to the retinal pigment epithelium, accumulations of material internal (vitread to) this layer can display a drusen-like appearance, having been variously termed pseudodrusen or subretinal drusenoid deposits. This review first briefly presents an overview of drusen biogenesis and subclinical deposit. The (frequently overlapping) subtypes of clinically detectable deposit, seen usually in the context of ageing or AMD, are then described in more detail, together with appearance on imaging modalities: these include hard and soft drusen, cuticular drusen, reticular pseudodrusen and "ghost drusen". Eye disorders other than AMD which may exhibit drusen or drusen-like features are subsequently discussed: these include monogenic conditions as well as conditions with undefined inheritance, the latter including some types of early onset drusen such as large colloid drusen. A number of systemic conditions in which drusen-like deposits may be seen are also considered. Throughout this review, high resolution images are presented for most of the conditions discussed, particularly the rarer ones, providing a useful reference library for images of the range of conditions associated with drusen-like appearances. In the final section, some common themes are highlighted, as well as a brief discussion of some future avenues for research.

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“…The two fitted lines show similar slopes with a mutual difference of less than 5%, which proves the consistency of the PAM imaging and segmentation algorithm. Since the RPE cell suffers from morphology changes and melanosomes leaking at the early state of the diseases such as AMD [5] , the calculated distributions of cell area, intensity, and their correlation can be promising indicators for detecting cell abnormality caused by diseases.…”

Section: (D) and 4(h)mentioning

confidence: 99%

“…To achieve the cellular or subcellular imaging level, PAM systems have been developed to achieve micrometer or submicrometer resolution and used for imaging red blood cells and pigment cells [7,14,15] . Since the photoacoustic (PA) signals of RPE are mostly generated from the strong light absorption of the pigment components, especially the melanin, the PAM can display the cell morphology, and more importantly, indicate the melanin content in cells [16] , which is highly correlated with aging and retinal diseases such as age-related macular degeneration (AMD) [5,17] . To acquire the RPE cell features such as morphology and component content, accurate cell detection and segmentation in cellular images are important.…”

mentioning

confidence: 99%

“…RPE has the function of transportation of nutrients and metabolic products between photoreceptors and blood [1,2] . Thus, it plays an important role in the maintenance of retinal homeostasis and is implicated in a majority of retinal diseases due to the failure of RPE functions [3][4][5] . An imaging method to examine RPE cells for retinal pathological analysis is needed.…”

mentioning

confidence: 99%

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Automated segmentation and quantitative study of retinal pigment epithelium cells for photoacoustic microscopy imaging

Dai

et al. 2017

Chin. Opt. Lett.

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We develop an improved region growing method to realize automatic retinal pigment epithelium (RPE) cell segmentation for photoacoustic microscopy (PAM) imaging. The minimum bounding rectangle of the segmented region is used in this method to dynamically update the growing threshold for optimal segmentation. Phantom images and PAM imaging results of normal porcine RPE are applied to demonstrate the effectiveness of the segmentation. The method realizes accurate segmentation of RPE cells and also provides the basis for quantitative analysis of cell features such as cell area and component content, which can have potential applications in studying RPE cell functions for PAM imaging.OCIS Retinal pigment epithelium (RPE) is a monolayer of pigmented cells located between photoreceptor outer segments and Bruch's membrane. RPE has the function of transportation of nutrients and metabolic products between photoreceptors and blood [1,2] . Thus, it plays an important role in the maintenance of retinal homeostasis and is implicated in a majority of retinal diseases due to the failure of RPE functions [3][4][5] . An imaging method to examine RPE cells for retinal pathological analysis is needed.Photoacoustic microscopy (PAM) is a noninvasive and label-free three-dimensional imaging modality based on the optical absorption property of biological tissues [6][7][8][9] , which has proved its capacity for in vivo imaging of blood vessels and RPE in fundus [10][11][12][13] . To achieve the cellular or subcellular imaging level, PAM systems have been developed to achieve micrometer or submicrometer resolution and used for imaging red blood cells and pigment cells [7,14,15] . Since the photoacoustic (PA) signals of RPE are mostly generated from the strong light absorption of the pigment components, especially the melanin, the PAM can display the cell morphology, and more importantly, indicate the melanin content in cells [16] , which is highly correlated with aging and retinal diseases such as age-related macular degeneration (AMD) [5,17] . To acquire the RPE cell features such as morphology and component content, accurate cell detection and segmentation in cellular images are important. In previous work, several semi-automatic and automatic cell segmentation methods have been used for cell evaluation, and they acquired remarkable results in the images of corneal endothelium, photoreceptor, and RPE cells [18][19][20][21][22][23][24] , using two-photon fluorescence microscopy, confocal microscopy, and adaptive optics retinal imaging. As these imaging results cannot provide melanin content information of RPE cells, an automatic RPE cell segmentation algorithm for PAM imaging is necessary.In our previous work [15] , RPE cells were imaged using dual modal PAM and optical coherence tomography (OCT). An ordinary region growing method was applied to segment RPE cells in PAM images by utilizing the connectivity of the relatively similar signal intensities within each cell. But the ordinary region growing method is limited as static predefin...

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The Project MACULA Retinal Pigment Epithelium Grading System for Histology and Optical Coherence Tomography in Age-Related Macular Degeneration

Cited by 130 publications

References 139 publications

Involvement of a gut–retina axis in protection against dietary glycemia-induced age-related macular degeneration

Involvement of a gut–retina axis in protection against dietary glycemia-induced age-related macular degeneration

Differentiating drusen: Drusen and drusen-like appearances associated with ageing, age-related macular degeneration, inherited eye disease and other pathological processes

Automated segmentation and quantitative study of retinal pigment epithelium cells for photoacoustic microscopy imaging

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