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Zai-Long Chi; The role of SRGAP2 in glaucomatous optic neuropathy. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3736.
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© ARVO (1962-2015); The Authors (2016-present)
Glaucoma is the leading cause of irreversible blindness worldwide which characterized by progressive retinal ganglion cell (RGC) degeneration and vision loss. The pathogenesis of glaucoma is poorly understood. SLIT-ROBO Rho GTPase-activating protein 2 (SRGAP2) plays a pivotal role in the central nervous system while its function in the retina is unclear. In order to explore the biological basis of SRGAP2, we combined gene knock out (KO) mice and optic nerve crush (ONC) models to investigate its function on RGC survival.
All animal experiments were conducted in compliance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. We generated SRGAP2 KO mice using CRISPER/CAS9 technology with the C57BL/6J background. Immunohistochemical and optical coherence tomography (OCT) analysis were performed for phenotype study after ONC. Electroretinogram (ERG) analysis was performed for assessment of retinal function. Stable SRGAP2 knockdown cell line was generated using lentivirus-mediated RNA interference. Western blotting analysis was performed against PI3K-AKT-mTOR and JAK-STAT3 signaling pathway. Two-tailed Student's t-test was used for statistical analysis.
SRGAP2 was expressed broadly in the neural retina, whereas especially higher in RGCs. Expression of SRGAP2 were increased significantly in the retina of C57BL/6J mice. SRGAP2 KO mice (n=4) observed prevention of RGC loss compared to wild type controls (n=6) 7 days after ONC (p=0.023). OCT analysis showed the thicker retina in KO mice (n=8) especially in the RGC and IPL layers as compared to wild type (n=12) after surgery (p=0.01). In addition, ERG analysis demonstrated that the retinal function was restored dramatically in KO mice one week after ONC (n=7 each group, p=0.002). Stable SRGAP2 knockdown cell line studies have revealed increased phosphorylation of AKT, mTOR, S6 and STAT3.
SRGAP2 may play an important role in the retinal development and neurodegeneration through regulating PI3K-AKT-mTOR and JAK-STAT3 signaling pathway.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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