VGF nerve growth factor inducible is involved in retinal ganglion cells death induced by optic nerve crush

Hiroto Takeuchi,Takahiro Mizoguchi,Yukimichi Nakano,Hideaki Hara,Masamitsu Shimazawa,Satoshi Inagaki,Yoshiki Kuse,Hideo Kaneko,Yuki Inoue,Michinori Funato,Wataru Morozumi,Shinsuke Nakamura

doi:10.1038/s41598-018-34585-3

Hiroto Takeuchi, Takahiro Mizoguchi + Show 10 more

Open Access

https://doi.org/10.1038/s41598-018-34585-3

Copy DOI

Abstract

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.

Highlights

Retinal ganglion cells (RGCs) are the retinal neurons transmit the visual information to the brain through the optic nerve[1]
The results showed that VGF was associated with the retinal and optic nerve degeneration induced by the optic nerve crush (ONC), and that AQEE-30 had neuroprotective effects against the ONC
We found that the expression of the mRNA of the Vgf gene and the VGF protein were upregulated after the ONC

Summary

Introduction

Retinal ganglion cells (RGCs) are the retinal neurons transmit the visual information to the brain through the optic nerve[1]. In the optic nerve crush (ONC) model, the axonal degeneration resulting in death of RGCs occurs via directly damage to optic nerve[13,14,15,16]. We found that SUN N8075 was able to induce the expression of VGF nerve growth factor inducible (VGF), and it was found to be neuroprotective against the endoplasmic reticulum (ER) stress-induced cell death[21]. In neuronal and neuroendocrine cells, VGF peptides including NERP-1, NERP-2, TLQP-21, LQEQ-19, and AQEE-30 are processed by the prohormone convertases[24,25,26]. These peptides have been shown to regulate neuronal activity such as synaptic plasticity, neurogenesis, and neuritis growth. The measurements of the intensity of the (D) whole retina, (E) retinal nerve fiber layer plus ganglion cell layer (RNFL + GCL), and (F)

Objectives

Methods

Results

Conclusion