GAD1 alleviates injury-induced optic neurodegeneration by inhibiting retinal ganglion cell apoptosis.

Yanping Zhu, Ya Zhang, Xiaoying Qi, Ying Lian, Hongyu Che, Jingdan Jia, Chunhua Yang, Yuxue Xu, Xiaodong Chi, Wenguo Jiang, Yanuo Li, Jia Mi, Yunfan Yang, Xuri Li, Geng Tian

Experimental eye research 2022 Oct

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The degeneration of the optic nerve narrows the visual field, eventually causing overall vision loss. This study aimed to identify global protein changes in the retina of optic nerve crushing (ONC) mice and to identify key regulators and pathways involved in injury-induced cell death during the progression of optic neurodegeneration. Label-free quantitative proteomics combined with bioinformatic analysis was performed on retinal protein extracts from ONC and sham-operated mice. Among the 1433 proteins detected, 121 proteins were differentially expressed in the retina of ONC mice. Further bioinformatic analysis showed that various metabolic pathways, including glutamate metabolism and γ-aminobutyric acid (GABA) synthesis, were significantly dysregulated in the injured mouse retinas. Glutamate decarboxylase 1 (GAD1) is the enzyme that converts glutamate into GABA, which was significantly up-regulated during ONC injury. Exogenous GAD1 treatment increased retinal ganglion cell (RGC) survival in the ONC-injured retina. In addition, changes in GAD1 expression were also observed in several other ophthalmic diseases. Vascular endothelial growth factor B (VEGF-B) has previously been reported to protect RGCs from apoptosis and positively regulated the expression of GAD1 in the retina. Notably, combination treatment with GAD1 and VEGF-B also provided strong protection against injury-induced RGC apoptosis. These results suggest that GAD1 expression may serve as an intrinsic protective mechanism that is commonly activated during retinal injury. Targeting GAD1 may serve as a potential strategy to treat optic neurodegenerative diseases. Copyright © 2022 Elsevier Ltd. All rights reserved.

Citation

Yanping Zhu, Ya Zhang, Xiaoying Qi, Ying Lian, Hongyu Che, Jingdan Jia, Chunhua Yang, Yuxue Xu, Xiaodong Chi, Wenguo Jiang, Yanuo Li, Jia Mi, Yunfan Yang, Xuri Li, Geng Tian. GAD1 alleviates injury-induced optic neurodegeneration by inhibiting retinal ganglion cell apoptosis. Experimental eye research. 2022 Oct;223:109201