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X. Liu, D. Wang, Y. Liu, Y. Luo, Q. Yu; The Role of NGF in Retinal Neovascularization in an Oxygen Induced Retinopathy Model. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5083.
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To evaluate the role of nerve growth factor (NGF) in retinal neovascularization in an oxygen-induced retinopathy (OIR) model.
The OIR model was established in C57BL/6J mice. NGF mRNA expression in retina was measured by Quantitative Real-Time PCR. NGF expression in protein level was evaluated by ELISA and immunostaining with NGF antibody. The effects of NGF on retinal neovascularization were evaluated by intravitreal injections of exogenous NGF and TrkA receptor inhibitor K252a, respectively, in an OIR model. Retinal neovascularization was measured by counting neovascular cell nuclei above the internal limiting membrane and by image quantification analysis in flat-mounted retinas perfused with fluorescein dextran.
NGF mRNA in retina had significantly high expression at postnatal day 17 (P17) in the OIR model compared to the normally developing mice. Similarly, ELISA and immunostaining assay showed a significantly increased NGF expression in retina at P17 in OIR mice, but no significant difference at P12 or P24 compared to normal controls. Exogenous NGF intraocular injection enhanced angiogenesis in the retina in the OIR model; however, injection with K252a, a high-affinity trkA receptor inhibitor, significantly decreased retinal neovascularization compared to that seen in the controls.
NGF contributed to the retinal neovascularization in the OIR model. Intravitreal injection with K252a, the trkA receptor inhibitor, reduced neovascularization, showing the potential therapeutic efficacy of NGF receptor inhibitor in OIR mice.This study provides new evidence that NGF, as a neurotrophic factor, potentially has angiogenic functions in ischemic retinopathy, representing a further and previously unveiled effect of NGF in retinal neovascularization. The finding increases our opportunity to discover new therapeutic strategies through inhibiting the angiogenic function of NGF in the retinal neovascularization
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