Angioid streaks associated with abetalipoproteinemia

Gorin, M.B.; Paul, T.; Dj, Rader

doi:10.3109/13816819409057843

Cited by 20 publications

(7 citation statements)

References 28 publications

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“…BLinD is a thin layer of soft druse material, in the same compartment. This framework facilitates explaining the participation of basal laminar deposit (BLamD) in clinical AMD, the trajectory of type 1 (subRPE-BL) neovascularization, the differing embryologic origins of RPE-BL versus ICL+EL+OCL, and Mendelian disorders preferentially affecting the RPE-BL28–30 versus structural elastin and collagen 31,32. By this definition, the Oil Spill in aging BrM33 becomes the Oil Spill on BrM.…”

Section: Defining the Layers Of Amdmentioning

confidence: 99%

Soft Drusen in Age-Related Macular Degeneration: Biology and Targeting Via the Oil Spill Strategies

Curcio

2018

Invest. Ophthalmol. Vis. Sci.

263

273

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AMD is a major cause of legal blindness in older adults approachable through multidisciplinary research involving human tissues and patients. AMD is a vascularmetabolic-inflammatory disease, in which two sets of extracellular deposits, soft drusen/ basal linear deposit (BLinD) and subretinal drusenoid deposit (SDD), confer risk for end-stages of atrophy and neovascularization. Understanding how deposits form can lead to insights for new preventions and therapy. The topographic correspondence of BLinD and SDD with cones and rods, respectively, suggest newly realized exchange pathways among outer retinal cells and across Bruch's membrane and the subretinal space, in service of highly evolved, eyespecific physiology. This review focuses on soft drusen/BLinD, summarizing evidence that a major ultrastructural component is large apolipoprotein B,E-containing, cholesterol-rich lipoproteins secreted by the retinal pigment epithelium (RPE) that offload unneeded lipids of dietary and outer segment origin to create an atherosclerosis-like progression in the subRPEbasal lamina space. Clinical observations and an RPE cell culture system combine to suggest that soft drusen/BLinD form when secretions of functional RPE back up in the subRPE-basal lamina space by impaired egress across aged Bruch's membrane-choriocapillary endothelium. The soft drusen lifecycle includes growth, anterior migration of RPE atop drusen, then collapse, and atrophy. Proof-of-concept studies in humans and animal models suggest that targeting the ''Oil Spill in Bruch's membrane'' offers promise of treating a process in early AMD that underlies progression to both end-stages. A companion article addresses the antecedents of soft drusen within the biology of the macula.

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Section: Defining the Layers Of Amdmentioning

confidence: 99%

Soft Drusen in Age-Related Macular Degeneration: Biology and Targeting Via the Oil Spill Strategies

Curcio

2018

Invest. Ophthalmol. Vis. Sci.

263

273

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“…ABL retinopathy involves macula and/or periphery and includes pigmentary changes, reduced electro-oculograms from RPE, reduced electroretinograms from cones and rods, predilection for angioid streaks (fractures in BrM) (70), and RPE cells with trilaminar inclusions in the subretinal space (71). For two decades, ABL retinopathy was attributed to systemic insufficiency of vitamin E transported by dietary apoB-containing lipoprotein (72).…”

Section: Discussionmentioning

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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“…Mutations of the MTP gene cause a rare autosomal recessive disorder, abetalipoproteinemia (ABL, MIM 200100, Bassen-Kornzweig disease). In addition to absent plasma apoB-lipoprotein ( 114,115 ), ABL features a retinopathy with pigmentary changes, reduced electro-oculogram and electroretinogram signals, and a predilection for angioid streaks (fractured BrM) ( 116,117 ). Truncating mutations of the APOB gene cause hypobetalipoproteinemia (HBL, MIM 107730), a genetically heterogeneous autosomal trait primarily characterized by asymptomatic low plasma LDL ( 118 ) and a retinal degeneration ( 119,120 ).…”

Section: Source Of Lipids Found In Rpe Lipoproteinsmentioning

confidence: 99%

Apolipoprotein B-containing lipoproteins in retinal aging and age-related macular degeneration

Curcio

Johnson

Huang

et al. 2010

Journal of Lipid Research

166

145

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Angioid streaks associated with abetalipoproteinemia

Cited by 20 publications

References 28 publications

Soft Drusen in Age-Related Macular Degeneration: Biology and Targeting Via the Oil Spill Strategies

Soft Drusen in Age-Related Macular Degeneration: Biology and Targeting Via the Oil Spill Strategies

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

Apolipoprotein B-containing lipoproteins in retinal aging and age-related macular degeneration

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