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


CONCLUSIONS
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.
Bhutto
Imran A
IA
Wilmer Ophthalmological Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287-9115, USA.
Uno
Koichi
K
Merges
Carol
C
Zhang
Lei
L
McLeod
D Scott
DS
Lutty
Gerard A
GA
D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000378:metabolism*; D016570:Bruch Membrane / Q000378:metabolism*; D020256:Choroidal Neovascularization / Q000503:physiopathology; D043169:Endostatins / Q000378:metabolism*; D005136:Eye Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008266:Macula Lutea / Q000378:metabolism; D008268:Macular Degeneration / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000378:metabolism*; D010857:Pigment Epithelium of Eye / Q000378:metabolism; D015843:Serpins / Q000378:metabolism*; D019700:Thrombospondin 1 / Q000378:metabolism*; D000099174:Pigment Epithelium-Derived Factor
D020533:Angiogenesis Inhibitors; D043169:Endostatins; D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D019700:Thrombospondin 1; D000099174:Pigment Epithelium-Derived Factor