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(American Journal of Pathology. 1998;153:1641-1646.)
© 1998 American Society for Investigative Pathology

Animal Models

Targeted Disruption of the FGF2 Gene Does Not Prevent Choroidal Neovascularization in a Murine Model

Takao Tobe* , Sagrario Ortega{dagger} , Jose D. Luna* , Hiroaki Ozaki* , Naoyuki Okamoto* , Nancy L. Derevjanik* , Stanley A. Vinores* , Claudio Basilico{dagger} and Peter A. Campochiaro*

From the Departments of Ophthalmology and Neuroscience,* The Johns Hopkins University School of Medicine, Baltimore, Maryland, and the Department of Microbiology and Kaplan Cancer Center,{dagger} New York University School of Medicine, New York, New York

Choroidal neovascularization (CNV) is the major cause of severe visual loss in patients with age-related macular degeneration. Laser treatment is helpful for a minority of patients with CNV, and development of new treatments is hampered by a poor understanding of the molecular signals involved. Several lines of evidence have suggested that basic fibroblast 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 CNV. 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, CNV was detected in 9 of 10 burns (90%) in which a bubble had been observed at the time of the laser treatment. Electron microscopy showed fenestrated vessels with large lumens within choroidal neovascular lesions. Two weeks after laser-induced rupture of Bruch's membrane, 27 of 36 burns (75%) contained CNV in FGF2-deficient mice compared with 26 of 30 (87%) in wild-type control mice, a difference that is not statistically significant. This study demonstrates that FGF2 is not required for the development of CNV after laser-induced rupture of Bruch's membrane and provides a new model to investigate molecular mechanisms and anti-angiogenic therapy in CNV.




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