The effect of VGF nerve growth factor inducible on retinal ganglion cell injury after optic nerve crush in mice

Abstract

Purpose : VGF nerve growth factor inducible (VGF), a polypeptide upregulated by neurotrophic factors, facilitates neuronal survival, neurogenesis, neuronal activity and neuritis growth. The involvement of VGF for retinal ganglion cells (RGCs) survival is still unknown, although the Vgf mRNA expression has been identified in the adult mouse retina. Therefore, the purpose of this study was to elucidate VGF dynamics in the retina and the involvement in RGCs survival in the optic nerve crush (ONC) model used as an experimental glaucoma model.

Methods : The expression of the Vgf mRNA and the VGF protein after the ONC was determined by real-time PCR, and the site of VGF expression was determined by immunostaining. The effect of AQEE-30, a VGF peptide, for RGCs was evaluated by using in vivo ONC model and in vitro RGCs analysis. In ONC model, the number of fluorogold-labeled RGCs was evaluated by counting on the loss of RGCs. Moreover, the effect of AQEE-30 for in vitro RGCs was evaluated by Tuj1-positive neurite outgrowth on rat-derived primary cultured RGCs and human induced pluripotent stem cells (iPSCs)-derived RGCs-like cells.

Results : After the ONC, the Vgf mRNA and the VGF protein were increased in the retina. Immunostaining showed that the VGF was localized in glial cells including the Müller glia and astrocytes, but less in the retinal neurons and their axons. Intravitreal injection of AQEE-30 inhibited the loss of RGCs after the ONC, and it enhanced neurite outgrowth of rat primary RGCs and iPSCs-derived RGCs-like cells.

Conclusions : These findings indicate that VGF plays important roles in the survival and activity of RGCs. Therefore, VGF has the potential to be a novel therapeutic target for glaucoma.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.