Targeted disruption of the FGF2 gene does not prevent choroidal neovascularization in a murine model

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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1641-1646
Number of pages6
JournalAmerican Journal of Pathology
Volume153
Issue number5
DOIs
StatePublished - Nov 1998

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Tobe, T., Ortega, S., Luna, J. D., Ozaki, H., Okamoto, N., Derevjanik, N. L., Vinores, S. A., Basilico, C., & Campochiaro, P. A. (1998). Targeted disruption of the FGF2 gene does not prevent choroidal neovascularization in a murine model. American Journal of Pathology, 153(5), 1641-1646. https://doi.org/10.1016/S0002-9440(10)65753-7