Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, Gifu, Japan.
Department of Clinical Research, National Hospital Organization, Nagara Medical Center, Gifu, Japan.
Sci Rep. 2018 Nov 6;8(1):16443. doi: 10.1038/s41598-018-34585-3.
VGF nerve growth factor inducible (VGF) is a polypeptide that is induced by neurotrophic factors and is involved in neurite growth and neuroprotection. The mRNA of the Vgf gene has been detected in the adult rat retina, however the roles played by VGF in the retina are still undetermined. Thus, the purpose of this study was to determine the effects of VGF on the retinal ganglion cells (RGCs) of mice in the optic nerve crush (ONC) model, rat-derived primary cultured RGCs and human induced pluripotent stem cells (iPSCs)-derived RGCs. The mRNA and protein of Vgf were upregulated after the ONC. Immunostaining showed that the VGF was located in glial cells including Müller glia and astrocytes but not in the retinal neurons and their axons. AQEE-30, a VGF peptide, suppressed the loss of RGCs induced by the ONC, and it increased survival rat-derived RGCs and promoted the outgrowth of neurites of rat and human iPSCs derived RGCs in vitro. These findings indicate that VGF plays important roles in neuronal degeneration and has protective effects against the ONC on RGCs. Thus, VGF should be considered as a treatment of RGCs degeneration.
神经生长因子诱导型（VGF）是一种多肽，可被神经营养因子诱导，参与神经突生长和神经保护。Vgf 基因的 mRNA 已在成年大鼠视网膜中检测到，但 VGF 在视网膜中的作用仍未确定。因此，本研究旨在确定 VGF 在视神经挤压（ONC）模型、大鼠原代培养的 RGC 和人诱导多能干细胞（iPSC）衍生的 RGC 中对小鼠视网膜神经节细胞（RGC）的作用。ONC 后 Vgf 的 mRNA 和蛋白表达上调。免疫染色显示 VGF 位于神经胶质细胞中，包括 Müller 胶质细胞和星形胶质细胞，但不在视网膜神经元及其轴突中。VGF 肽 AQEE-30 抑制 ONC 诱导的 RGC 丢失，并增加存活的大鼠来源的 RGC 数量，促进大鼠和人 iPSC 衍生的 RGC 的神经突生长。这些发现表明 VGF 在神经元变性中发挥重要作用，并对 RGC 的 ONC 具有保护作用。因此，VGF 可被视为 RGC 变性的治疗方法。
