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 journalArticlepeer-review

1 Scopus citations

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)
Pages (from-to)698-709
Number of pages12
JournalMolecular Neurobiology
Volume57
Issue number2
DOIs
StatePublished - Feb 1 2020

Keywords

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

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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