![]() ![]() The anatomic definition of BrM 27 is five layers (from inner to outer), RPE-basal lamina (BL) and inner collagenous, elastic, and outer collagenous layers (inner collagenous layer, elastic layer, outer collagenous layer ). ![]() 4Ī cellular- and molecular-level understanding of drusen begins with delicate tissue layers in the RPE-BrM-ChC complex and adjoining potential spaces ( Fig. 12, 13 A hypothesis that Müller cells are major xanthophyll reservoirs is explored separately. 10, 11 Xanthophyll pigments lutein and zeaxanthin are prominent in the foveal center, and lutein, in the Henle fiber and inner plexiform layers. Among numerous Müller cell functions 9 are recently recognized roles in delivering to cones for phototransduction vitamin A derivatives of dietary origin. The Henle fiber layer contains inner fibers of photoreceptors and Müller glia that form junctions at the external limiting membrane. The macular neurosensory retina consists of a 0.8-mm diameter all-cone fovea surrounded by a rod-dominated annulus of 6-mm outer diameter. Strong apical to basolateral polarization makes the RPE a key player in the homeostasis of photoreceptors and the pathology of SDD apically and choriocapillaris and the pathology of drusen basally. 8 The RPE is a monolayer of cuboidal polygonal cells embedded between photoreceptors and BrM. Between RPE and ChC is a laminated subendothelial extracellular matrix called Bruch's membrane (BrM), which functions as a vessel wall laid out flat, paralleling vascular lumens. The choroid has the highest blood flow in the body, and the choriocapillaris is sinusoidal and fenestrated. The cells and tissues most prominently affected by AMD pathology are those of the outer retinal neurovascular unit 7 (i.e., photoreceptors, RPE, Müller cells, and the choriocapillaris endothelium ). A companion article addresses the antecedents of soft drusen within the biology of the macula.Ī neurovascular unit 5, 6 comprises microvessels, neurons, glia, pericytes, and extracellular matrix that link blood flow to the metabolic demands of neurons. 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. The soft drusen lifecycle includes growth, anterior migration of RPE atop drusen, then collapse, and atrophy. 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. 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 subRPE-basal lamina space. 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, eye-specific physiology. ![]() Understanding how deposits form can lead to insights for new preventions and therapy. AMD is a vascular-metabolic-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. AMD is a major cause of legal blindness in older adults approachable through multidisciplinary research involving human tissues and patients. ![]()
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