Vps35 haploinsufficiency results in degenerative-like deficit in mouse retinal ganglion neurons and impairment of optic nerve injury-induced gliosis

Wei Liu, Fu Lei Tang, Joanna Erion, Hang Xiao, Jian Ye, Wen Cheng Xiong

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

VPS35 (vacuolar protein sorting 35) is a major component of retromer that selectively promotes endosome-to-Golgi retrieval of transmembrane proteins. Dysfunction of retromer is a risk factor for the pathogenesis of Parkinson's disease (PD) and Alzheimer's disease (AD), both neuro-degeneration disorders. However, VPS35/retromer's function in retina or the contribution of Vps35-deficiency to retinal neuro-degenerative disorders has not been investigated. Here we provide evidence for a role of VPS35 in mouse retinal ganglion cell (RGC) survival and regeneration. VPS35 is selectively expressed in developing mouse RGCs. RGCs from young adult Vps35 heterozygotes (Vps35 +/m) show degenerative-like features, such as dystrophic dendrites, reduced axon fibers, and increased TUNEL labeled RGCs. Additionally, gliosis in the optic nerve is transiently elevated in neonatal, but reduced in aged Vps35+/m mice. Optic nerve injury-induced gliosis is also attenuated in Vps35+/m mice. These results suggest that Vps35 is necessary for mouse RGC survival and regeneration, and Vps35-deficiency may contribute to the pathogenesis of retinal ganglion neuro-degeneration, a critical pathology leading to the blindness of many retinal degenerative disorders.

Original languageEnglish (US)
Article number10
JournalMolecular brain
Volume7
Issue number1
DOIs
StatePublished - Feb 11 2014

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Keywords

  • Neuro-degeneration
  • Optic nerve injury
  • Retinal ganglion cell
  • VPS35

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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