Objectives: To determine the relative levels of 3 potent inhibitors of angiogenesis (endostatin, pigment epithelium-derived factor, and thrombospondin 1) in the retinal pigment epithelium-Bruch's membrane-choriocapillaris complex in the submacular region in aged control eyes and eyes with age-related macular degeneration (AMD).

Methods: Immunohistochemical analysis with antibodies against endostatin, pigment epithelium-derived factor, and thrombospondin 1 was performed on the macular region of aged control donor eyes (n = 8; mean age, 79.8 years) and eyes with AMD (n = 12; mean age, 83.9 years). Three independent masked observers scored the reaction product (scored from 0-7). Mean scores from the control eyes and the eyes with AMD were analyzed using 1-way analysis of variance and unpaired t test.

Results: In control eyes, strong immunoreactivity of all 3 inhibitors was observed in the retinal pigment epithelium-Bruch's membrane-choriocapillaris complex. Immunoreactivity for endostatin, pigment epithelium-derived factor, and thrombospondin 1 in Bruch's membrane was significantly lower in eyes with AMD compared with aged control eyes (analysis of variance, P = .003, P = .009, and P < .001, respectively). In the choriocapillaris, a significant reduction was observed in endostatin (analysis of variance, P = .02) and thrombospondin 1 (analysis of variance, P = .005) in eyes with AMD.

Conclusions: These findings suggest that endogenous angiogenesis inhibitors in the retinal pigment epithelium-Bruch's membrane-choriocapillaris complex may provide a biochemical barrier for choroidal neovascular invasion.

Clinical Relevance: Decreased levels of angiogenic inhibitors at the retinal pigment epithelium-Bruch's membrane-choriocapillaris complex in eyes with AMD make Bruch's membrane vulnerable to choroidal neovascularization.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4943079PMC
http://dx.doi.org/10.1001/archopht.126.5.670DOI Listing

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