TARGETED DISRUPTION OF THE FGF2 GENE DOES NOT PREVENT CHOROIDAL NEOVASCULARIZATION IN A MURINE MODEL

Choroidal neovascularization (CNV) is the major cause of severe visual loss Ln patients with age-related macular degeneration. Laser treatme nt is helpful for a minority of patients with CNV, and development of new treatments is hampered by a poor understanding of the molecular si gnals involved. Several lines of evidence have suggested that basic fi broblast growth factor (FGF2) plays a role in stimulating CNV, In this study, we tested this hypothesis using mice with targeted disruption of the FGF2 gene in a newly developed murine model of laser-induced CN V, One week after krypton laser photocoagulation in C57BL/6J mice, 34 of 60 burns (57%) showed fluorescein leakage and 13 of 16 (81%) showed histopathological evidence of CNV, At 2 weeks, CMI was detected in 9 of 10 burns (90%) in which a bubble had been observed at the time of t he laser treatment. Electron microscopy showed fenestrated vessels wit h large lumens within choroidal neovascular lesions. Two weeks after l aser-induced rupture of Bruch's membrane, 27 of 36 burns (75%) contain ed CNV in FGF2-deficient mice compared with 26 of 30 (87%) in wild-typ e control mice, a difference that is not statistically significant. Th is study demonstrates that FGF2 is not required for the development of CNV after laser-induced rupture of Bruch's membrane and provides a ne w model to investigate molecular mechanisms and anti-angiogenic therap y in CNV.