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Christine A Curcio; What age-related macular degeneration taught us about aging of the retinal pigment epithelium. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© ARVO (1962-2015); The Authors (2016-present)
Presentation Description :
Age related macular degeneration (AMD) is third largest cause of vision loss globally. Advanced age is still the biggest risk factor despite breathtaking progress in understanding genetic and environmental factors. The retinal pigment epithelium (RPE) has demanding dual roles serving photoreceptors (as epithelium, glia, macrophage, hepatocyte) and choroidal vasculature. RPE decompensation is a key component of AMD pathobiology; these cells are targets for multiple molecular and cell-based therapies.Our research is based in accurate cellular maps revealing that the area most affected by aging and impacting vision is central macula on the inner slope of the rod ring. Here rod populations dwindle throughout normal adulthood while cones (tended by Müller cells) and RPE are maintained. Concomitantly rod-mediated dark adaptation, a function limited by chromophore availability from choroid, declines earlier and more rapidly than any other visual test and predicts incipient AMD. RPE accumulates bisretinoid-containing lipofuscin without cell loss in a manner that is spatially un-correlated with photoreceptor loss and is likely related to RPE-secreted lipoproteins retained in thickened Bruch’s membrane. RPE rearranges and loses lipofuscin in advanced age, precipitously in AMD. RPE fate in AMD goes beyond cell death to include transdifferentiation and migration, possibly including a pro-inflammatory phenotype. Remarkably, thanks to widely-available cellular level imaging, many of these processes are directly observable in living people.Aging of the outer retinal neurovascular unit and onset of AMD is arranged in delicate tissue layers that can be directly visualized for an accurate timeline of molecular pathogenesis. In the quest to dissect out and visualize RPE- and Bruch’s membrane-specific components, findings from 3 decades of collaborative studies utilizing population-based eye pathology (electron and fluorescence microscopy, gene expression, lipid profiling, histochemistry), visual function testing of rod and cone systems, multimodal imaging including optical coherence tomography and fundus autofluorescence, and epidemiology will be presented.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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