This Article  • Full text  • PDF  • eFigure  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Aging/ Geriatrics  • Choroidal Neovascularization  • Macular Degeneration  • Retinal/ Chorioretinal Disorders  • Alert me on articles by topic

Imran A. Bhutto, MD, PhD; Koichi Uno, MD, PhD; Carol Merges, MAS; Lei Zhang, ScM; D. Scott McLeod; Gerard A. Lutty, PhD

Arch Ophthalmol. 2008;126(5):670-678.

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 neovascularinvasion.

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.

Author Affiliations: Wilmer Ophthalmological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.