Reduction of endogenous angiogenesis inhibitors in Bruch's membrane of the submacular region in eyes with age-related macular degeneration

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.