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M.R. Castro, K.M. Harrison, J.L. Edelman; Apparent RPE Cell Dystrophy or Atrophy Is Associated With Subretinal Neovascular Lesions in a Primate Model of Laser–Induced CNV . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2163.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the temporal and anatomical relationship between choroidal and retinal vascular endothelial cells, RPE cells, and macrophages in a primate model of laser–induced choroidal neovascularization (CNV).
CNV lesions were induced by laser photocoagulation (460 mW, 100 ms, 100 µm), in both eyes (4–8 perimacular laser spots per eye) of seven female squirrel monkey (Saimiri sciureus), and they were evaluated weekly by fundus photography and late–phase fluorescein angiography through 4 weeks post–laser. Lesions from 1, 2, or 4 weeks post–laser (8–32 lesions per time point) were examined in cross–sectional histology with H&E staining and immunohistochemisty for Factor VIII, CD31, RPE65, and HAM56 labeling of vascular endothelial cells, functional RPE cells, and macrophages, respectively.
Laser–induced CNV lesions show persistent vascular leakage in late–phase fluorescein angiograms from 1 week through 4 weeks post–laser, and leakage appears maximal in lesions closer to the macula and as early as 1 week post–laser. Some proximally located lesions appear to coalesce with bridges of fluorescein leakage between them. CD31 or Factor VIII immunohistologic staining reproducibly labels choroidal vascular endothelial cells in all lesions and shows a similar extent of neovascularization from week 1 through week 4. Bridges between lesions observed angiographically are shown histologically by H&E, CD31, and Factor VIII to be proliferative neovascular membranes that penetrate the subretinal space and interconnect adjacent laser lesions. Immunostaining for RPE65 shows prominent labeling of normal RPE, a complete lack of RPE cells within the neovascular lesion, and a loss of RPE65 expression in RPE cells underlying the subretinal neovascular membranes that interconnect adjacent laser lesions. HAM56 immunolabeling shows macrophages associated with neovascular lesions from week 1 through week 4 post–laser.
Laser photocoagulation in the squirrel monkey induces aggressive subretinal neovascular lesions that are associated with macrophages but not with RPE cells. Subretinal neovascularization appears to result in the dystrophy or atrophy of RPE cells in this model.
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