Differential Gamma-Synuclein Expression in Acute and Chronic Retinal Ganglion Cell Death in the Retina and Optic Nerve
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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.
KeywordsGamma-synuclein DBA/2J Optic nerve crush Macrophage Scar formation
The Bascom Palmer Eye Institute is supported by the NIH Center Core Grant P30EY014801 and a Research to Prevent Blindness Unrestricted Grant. R.K. Lee is supported by the Walter G. Ross Foundation. This work was partially supported by the Guitierrez Family Research Fund and a research gift from the Vakil family.
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Conflict of Interest
The authors declare that they have no conflict of interest.
Statement on the Welfare of Animals
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice of the University of Miami Institutional Animal Care and Use Committee.
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