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G. A. Lutty, R. Grebe, I. A. Bhutto, M. Taomoto, C. A. Merges, D. S. McLeod; Death of Choriocapillaris in Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3518.
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Retinal pigment epithelial cells (RPE) and the choriocapillaris (CC) share a mutualistic relationship in that they depend on each other for their survival and efficient function. The initial pathological changes in age-related macular degeneration (AMD) occur in the RPE/ Bruchâ€TMs membrane/CC complex and in photoreceptor cells. Our goal was to quantify changes in the RPE/CC in choroids from eyes with geographic atrophy (GA), a form of dry AMD, and exudative AMD.
We have developed a technique that permits us to map and quantify viable RPE and viable CC (stained with endogenous alkaline phosphatase) in human postmortem choroids and study the relationship between RPE and CC atrophy (McLeod et al, Invest Ophthal. Vis. Sci. 43:1986, 2002). This method was used to measure % RPE area and % vascular area (VA) in choroids from 3 aged controls (mean age 78+ 7.2 yrs), 3 wet AMD (80.6+3.5), and 6 GA subjects (83+9.7).
In GA, surviving CC in areas with complete RPE atrophy is attenuated (38 +/- 5.7 % VA) compared to non-atrophic regions (70.3 +/- 2.9% VA). The surviving CC in regions of RPE atrophy was highly constricted compared to CC in non-atrophic regions (7.9 +/- 1.24 Î¼m versus 13.9 +/- 1.4 Î¼m lumenal diameters). In wet or exudative AMD cases, we found CC dropout extending well beyond the boundaries of RPE atrophy and vascular changes were also present in regions without any morphological changes in the RPE (39.63%VA in regions with 95.8 % RPE area) compared to aged controls (79.6%VA in regions with 95.7 % RPE area). The surviving capillaries in these regions were not constricted as compared with aged controls. CNV was always accompanied by viable RPE cells.
These studies demonstrate that the mutualistic relationship between RPE and CC is disrupted in AMD. We conclude that in GA, RPE atrophy occurs first followed by attenuation of the CC and vasoconstriction of surviving capillary segments. CC degeneration occurs in eyes with wet AMD in the absence of RPE atrophy. This suggests a vascular etiology for wet AMD. The association of surviving RPE cells with active CNV suggests that RPE cells may provide a stimulus for new vessel formation and survival.
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