Srgap2 suppression ameliorates retinal ganglion cell degeneration in mice

• Published in: Neural regeneration research Vol. 18; no. 10; pp. 2307 - 2314
• Main Authors: Gan, Yi-Jing, Cao, Ying, Zhang, Zu-Hui, Zhang, Jing, Chen, Gang, Dong, Ling-Qin, Li, Tong, Shen, Mei-Xiao, Qu, Jia, Chi, Zai-Long
• Format: Journal Article
• Language: English
• Published: India Wolters Kluwer India Pvt. Ltd 01.10.2023; Medknow Publications & Media Pvt. Ltd; Department of Ophthalmology,The First Affiliated Hospital of University of Science and Technology of China,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei,Anhui Province,China%State Key Laboratory of Ophthalmology,Optometry and Vision Science,Eye Hospital,Wenzhou Medical University,Wenzhou,Zhejiang Province,China; State Key Laboratory of Ophthalmology,Optometry and Vision Science,Eye Hospital,Wenzhou Medical University,Wenzhou,Zhejiang Province,China; Wolters Kluwer - Medknow
• Subjects: Heat shock proteins; Kinases; Optic nerve; Retina; Srgap2; neuroprotection; mTOR; optic neuropathy; intraocular hypertension; crystallins; optic nerve crush; RGC degeneration; astrocyte; microglia
• ISSN: 1673-5374; 1876-7958
• DOI: 10.4103/1673-5374.369122

[INLINE:1] Slit-Robo GTPase-activating protein 2 (SRGAP2) plays important roles in axon guidance, neuronal migration, synapse formation, and nerve regeneration. However, the role of SRGAP2 in neuroretinal degenerative disease remains unclear. In this study, we found that SRGAP2 protein was first expressed in the retina of normal mice at the embryonic stage and was mainly located in the mature retinal ganglion cell layer and the inner nuclear layer. SRGAP2 protein in the retina and optic nerve increased after optic nerve crush. Then, we established a heterozygous knockout (Srgap2+/-) mouse model of optic nerve crush and found that Srgap2 suppression increased retinal ganglion cell survival, lowered intraocular pressure, inhibited glial cell activation, and partially restored retinal function. In vitro experiments showed that Srgap2 suppression activated the mammalian target of rapamycin signaling pathway. RNA sequencing results showed that the expression of small heat shock protein genes (Cryaa, Cryba4, and Crygs) related to optic nerve injury were upregulated in the retina of Srgap2+/- mice. These results suggest that Srgap2 suppression reduced the robust activation of glial cells, activated the mammalian target of rapamycin signaling pathway related to nerve protein, increased the expression of small heat shock protein genes, inhibited the degeneration of retinal ganglion cells, and partially restored optic nerve function.