Renewal of photoreceptor outer segments and their phagocytosis by theretinal pigment epithelium

Nguyen‐Legros, Jeanine; Hicks, David

doi:10.1016/s0074-7696(00)96006-6

Cited by 137 publications

(92 citation statements)

References 250 publications

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“…In this ultrastructural investigation, some end feet of Müller cells show a phagocytic feature. In the normal retina, debris of neurons in the inner retina are engulfed and digested by microglial cells, whereas photoreceptor debris are incorporated by pigment epithelial cells [35,36]. Microglial cells in the diabetic retina showed shape changes before the leakage of the blood-retinal barrier indicating their functional activation [37].…”

Section: Discussionmentioning

confidence: 99%

Apoptotic death of photoreceptors in the streptozotocin-induced diabetic rat retina

et al. 2003

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Aims/hypothesis. Neurodegenerative changes in the diabetic retina occurring before diabetic retinopathy could be inevitable by the altered energy (glucose) metabolism, in the sense that dynamic image-processing activity of the retinal neurons is exclusively dependent on glucose. We therefore investigated the morphological changes in the neural retina, including neuronal cell death, of a streptozotocin-induced model of diabetes. Methods. Streptozotocin was intravenously injected. Rats were maintained hyperglycaemic without insulin treatment for 1 week and 4, 8, 12, and 24 weeks, respectively. Diabetic retinas were processed for histology, electron microscopy, and immunohistochemistry using the TUNEL method. Results. A slight reduction in the thickness of the inner retina was observed throughout the diabetic retinas and a remarkable reduction was seen in the outer nuclear layer 24 weeks after the onset of diabetes.The post-synaptic processes of horizontal cells in the deep invaginations of the photoreceptors showed degeneration changes from 1 week onwards. A few necrotic ganglion cells were observed after 4 weeks. At 12 weeks, some amacrine cells and a few horizontal cells showed necrotic features. Three to seven cellular layers in the outer nuclear layer and nerve terminals, rolled by the fine processes of the Müller cells near the somata of the degenerated ganglion cells, were apparent at 24 weeks. Apoptosis appeared in a few photoreceptor cells at 4 weeks, and the number of apoptotic photoreceptors increased thereafter. Conclusion/interpretation. These findings suggest that the visual loss associated with diabetic retinopathy could be attributed to an early phase of substantial photoreceptor loss, in addition to later microangiopathy. [Diabetologia (2003[Diabetologia ( ) 46:1260[Diabetologia ( -1268

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Section: Discussionmentioning

confidence: 99%

Apoptotic death of photoreceptors in the streptozotocin-induced diabetic rat retina

et al. 2003

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“…This process, which involves RPE phagocytosis, causes up to 10% photoreceptor volume loss each day and is entrained to the circadian rhythm. 14,15 Indeed there is increasing interest in the role of autophagy in preserving photoreceptor function in connection with the circadian cycle, 16 the aging process, 17 and retinal disease pathology. 18 It is therefore likely that the absence of DRAM2 in the retina reduces the efficiency of autophagy in recycling cell components, which in turn reduces photoreceptor renewal, leading to the thin photoreceptor layer observed on OCT, which is the first presenting feature in pre-symptomatic patients.…”

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confidence: 99%

Biallelic Mutations in the Autophagy Regulator DRAM2 Cause Retinal Dystrophy with Early Macular Involvement

El‐Asrag

Sergouniotis

McKibbin

et al. 2015

The American Journal of Human Genetics

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“…Studies of BrM lipid composition (11,12,15) implicate extravasation of plasma lipoproteins from the choroid or deposition from intraocular cells as candidate mechanisms. The RPE processes abundant lipids from ingested OS membranes (16). It synthesizes and secretes BrM constituents (17,18) and contains biosynthetic machinery for numerous druse-associated proteins (19,20), including apoE (6,21).…”

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confidence: 99%

Retina expresses microsomal triglyceride transfer protein: implications for age-related maculopathy

Presley

Zhang

et al. 2005

Journal of Lipid Research

105

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The principal extracellular lesions of age-related maculopathy (ARM), the leading cause of vision loss in the elderly, involve Bruch's membrane (BrM), a thin vascular intima between the retinal pigment epithelium (RPE) and its blood supply. With age, 80-100 nm solid particles containing esterified cholesterol (EC) accumulate in normal BrM, and apolipoprotein B (apoB) immunoreactivity is detectable in BrM-and ARM-associated lesions. Yet little evidence indicates that increased plasma cholesterol is a risk factor for ARM. To determine if RPE is capable of assembling its own apoB-containing lipoprotein, we examined RPE for the expression of microsomal triglyceride transfer protein (MTP), which is required for this process. Embryologically part of the central nervous system, the retina ( Fig. 1A ) converts light energy to electrochemical signals for transmission to the brain. The photoreceptors are supported by the retinal pigment epithelium (RPE), a monolayer with diverse functions including daily phagocytosis of the distal tips of photoreceptor outer segments (OS), and the choroid, a vascular bed with the body's highest blood flow. The choriocapillaris is a dense capillary plexus in the innermost choroid, and Bruch's membrane (BrM) is a thin vascular intima between the RPE and the choriocapillaris (Fig. 1B, arrowheads). In human retina, the macula subserves high-acuity vision and is vulnerable to age-related maculopathy (ARM), the major cause of vision loss among the elderly of industrialized societies. The most prominent histopathologic and clinical signs of ARM are extracellular lesions [drusen (Fig. 1E, F) and basal linear deposits (not shown)] in the RPE/BrM complex that ultimately impact vision by the photoreceptors (1, 2). Choroidal neovascularization, an invasion of choriocapillaries across BrM and lateral spread within the plane of drusen and basal linear deposit (see 3), is the principal sight-threatening complication of ARM's obscure underlying degeneration.Recent findings highlight a role for lipids and lipoproteins in this degeneration. These include a protective effect of the apolipoprotein E4 (apoE4) genotype in populations and the presence of apoB and apoE and histochemically identified lipids in aging-and ARM-associated drusen and deposits in human tissues (4-8) (Fig. 1E, F). The best established risk factor for early ARM is advanced age (9). A Abbreviations: ABL, abetalipoproteinemia; apoB, apolipoprotein B; apoBEC-1, apolipoprotein B-editing complex-1; ARM, age-related maculopathy; BrM, Bruch's membrane; EC, esterified cholesterol; ESI/MS, electrospray ionization mass spectrometry; INL, inner nuclear layer; MCT3, monocarboxylate transporter 3; MTP, microsomal triglyceride transfer protein; OS, outer segments of photoreceptors; RGC, retinal ganglion cell; RPE, retinal pigment epithelium; TC, total cholesterol; TG, triglyceride; UC, unesterified cholesterol.

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Renewal of photoreceptor outer segments and their phagocytosis by theretinal pigment epithelium

Cited by 137 publications

References 250 publications

Apoptotic death of photoreceptors in the streptozotocin-induced diabetic rat retina

Apoptotic death of photoreceptors in the streptozotocin-induced diabetic rat retina

Biallelic Mutations in the Autophagy Regulator DRAM2 Cause Retinal Dystrophy with Early Macular Involvement

Retina expresses microsomal triglyceride transfer protein: implications for age-related maculopathy

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