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 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.
Tobe
T
T
Department of Ophthalmology and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-9277, USA.
Ortega
S
S
Luna
J D
JD
Ozaki
H
H
Okamoto
N
N
Derevjanik
N L
NL
Vinores
S A
SA
Basilico
C
C
Campochiaro
P A
PA
D000818:Animals; D002829:Choroid / Q000098:blood supply* / Q000648:ultrastructure; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000502:physiology*; D005451:Fluorescein Angiography; D007834:Lasers; D008028:Light Coagulation; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic
D016222:Fibroblast Growth Factor 2