Differential Gamma-Synuclein Expression in Acute and Chronic Retinal Ganglion Cell Death in the Retina and Optic Nerve

Yuan Liu, Mary L. Tapia, Justin Yeh, Rossana Cheng He, Dustin Pomerleu, Richard K Lee

Research output: Contribution to journalArticle

Abstract

We used genetic naturally occurring glaucoma (DBA/2J) and experimentally induced optic nerve crush (ONC) as models to study gamma-synuclein expression change in retinal ganglion cells and optic nerves. Gene chip microarray analysis demonstrated downregulated expression of the gamma-synuclein gene in DBA/2J mice as they developed age-associated glaucoma with concomitant with retinal ganglion cell loss. Real-time PCR, Western blot, and immunostaining results confirmed that the expression of gamma-synuclein at the mRNA and protein level was significantly reduced in the retinas and optic nerves of aged DBA/2J mice. We also observed similar reduced expression of gamma-synuclein in the retinas from mice after optic nerve crush. Surprisingly, the expression of gamma-synuclein was increased in optic nerves after crush. This is the first study demonstrating gamma-synuclein-expressing cells accumulate in the optic nerve crush site. Gamma-synuclein was found in axons colocalizing largely with neurofilaments in control mice without injury but was found inside cells within the scar in the crush site. Gamma-synuclein expression is predominantly expressed at the optic nerve crush site associated with CD68+ macrophage-like cells, not GFAP-expressing astroglial cells, suggesting gamma-synuclein expression is associated with glial scar formation inhibitory to optic nerve regeneration. We propose gamma-synuclein labels macrophage-like cells recruited to the site of acute optic nerve injury.

Original languageEnglish (US)
JournalMolecular Neurobiology
DOIs
StateAccepted/In press - Jan 1 2019

Keywords

  • DBA/2J
  • Gamma-synuclein
  • Macrophage
  • Optic nerve crush
  • Scar formation

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Neurology
  • Cellular and Molecular Neuroscience

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