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.
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Funding
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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Liu, Y., Tapia, M.L., Yeh, J. et al. Differential Gamma-Synuclein Expression in Acute and Chronic Retinal Ganglion Cell Death in the Retina and Optic Nerve. Mol Neurobiol 57, 698–709 (2020). https://doi.org/10.1007/s12035-019-01735-1
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DOI: https://doi.org/10.1007/s12035-019-01735-1