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Jeong Hun Kim, You Sun Kim, Hyunjae Lee, Sudong Kim, Noo Li Jeon, Jin Hyoung Kim; Nerve growth factor-mediated vascular endothelial growth factor expression of astrocyte in retinal vascular development. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5163.
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To investigate the role of neurotrophin receptors in retinal vascular development and the mechanisms of their actions.
Using developing mouse retina of postnatal 4, 8, 12, 16 and 28, histological examination with H&E staining was performed. In addition, immunofluorescence staining for TrkA, TrkB, collagen type IV and GFAP was performed. With treatment of recombinant nerve growth factor (NGF) in human brain astrocytes, Western blotting for TrkA, phosphor-Trk, Akt, and phosphor-Akt was performed. In addition, Vascular endothelial growth factor (VEGF) expression in astrocytes was evaluated with treatment of NGF by RT-PCR.
TrkA was expressed mainly along the vessel structure in inner part of retina, especially in retinal astrocyte. In cultured primary astrocyte, recombinant NGF was used to activate TrkA. NGF induced the phosphorylation of TrkA. Also it enhanced the level of activated Akt and VEGF mRNA. Inhibition of phosphoinositide 3-kinase (PI3K) reversed the NGF-induced activation of these two molecules.
Our results demonstrated that TrkA activation on NGF leads to VEGF elevation by PI3K-Akt pathway and therefore suggested that TrkA could be a stimulator of retinal vascular development.
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