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Yun-Zheng Le, Meili Zhu; VEGF receptor-2 mediated neuro-protection is required for cone photoreceptor survival under hypoxic condition. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3261.
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Vascular endothelial growth factor-A (VEGF-A or VEGF) is an essential growth factor required for vasculogenesis and angiogenesis in development and physiological processes in the eye. However, VEGF is also a major inducer for pathological angiogenesis in diabetic retinopathy (DR) and age-related macular degeneration (AMD). To determine the effect of long-term anti-VEGF treatments for pathological angiogenesis on cone photoreceptors, we conditionally disrupted VEGF receptor 2 (VEGFR2), major VEGF receptor in cones, and determined the effect of disrupting VEGFR2 on cone photoreceptor integrity under normal or hypoxic condition.
Cone-specific Vegfr2 knockout mice were derived by mating of floxed Vegfr2 mice with our cone-specific Cre mice. Retinal integrity in conditional Vegfr2 KO mice was determined by measuring cone density and photopic electroretinography (ERG) amplitudes. Hypoxia was induced by intravitreal delivery of chemical hypoxia inducer, cobalt chloride.
Cone-specific Vegfr2 KO mice did not shown any apparent alteration in retinal function and cone density normally. However, hypoxia-induced loss of cone densities and photopic ERG amplitudes was exacerbated in cone-specific Vegfr2 KO mice treated with cobalt chloride. Mechanistic Investigation on hypoxia-induced VEGFR2 mediated cone photoreceptor protection is in progress.
We have demonstrated that VEGF signaling through VEGFR2 is not required for cone photoreceptor survival under normal conditions. However, VEGFR2-mediated signaling is necessary for cone photoreceptor protection under hypoxic conditions. This result supports the notion that VEGF-VEGFR2 mediated neural protection may be required for cone photoreceptor survival in hypoxic retinas during the development of AMD and DR.
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