TY - JOUR
T1 - Reduction of endogenous angiogenesis inhibitors in Bruch's membrane of the submacular region in eyes with age-related macular degeneration.
AU - Bhutto, Imran A
AU - Uno, Koichi
AU - Merges, Carol
AU - Zhang, Lei
AU - McLeod, D Scott
AU - Lutty, Gerard A
PY - 2008
Y1 - 2008
N2 - 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).\n\nMETHODS: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.\n\nRESULTS: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.\n\nCONCLUSIONS: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.\n\nCLINICAL 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.
AB - 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).\n\nMETHODS: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.\n\nRESULTS: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.\n\nCONCLUSIONS: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.\n\nCLINICAL 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.
U2 - 10.1001/archopht.126.5.670
DO - 10.1001/archopht.126.5.670
M3 - Article
C2 - 18474778
SN - 0003-9950
VL - 126
SP - 670
EP - 678
JO - Archives of Ophthalmology
JF - Archives of Ophthalmology
IS - 5
ER -