Neuronal-Driven Angiogenesis: Role of NGF in Retinal Neovascularization in an Oxygen-Induced Retinopathy Model

Abstract

PURPOSE. To evaluate the role of nerve growth factor (NGF) in retinal neovascularization in an oxygen-induced retinopathy (OIR) model. METHODS. 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 levels 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. RESULTS. NGF mRNA in retina had significantly high expression at postnatal day (P)17 in the OIR model compared with normally developing mice. Similarly, ELISA and immunostaining assay showed significantly increased NGF expression in retina at P17 in OIR mice but no significant differences at P12 or P24 compared with 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 with that seen in the controls. CONCLUSIONS. NGF contributed to 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.