Translocator protein 18 kDa regulates retinal neuron apoptosis and pyroptosis in glaucoma.

May 01, 2023

Experts: Zhou Zeng,Mengling You,Rong Rong,Cong Fan,Meini Chen,Haibo Li,Dan Ji,Xiaobo Xia

Glaucoma is the leading cause of blindness worldwide. However, our insufficient understanding of the pathogenesis of glaucoma has limited the development of effective treatments. Because recent research has highlighted the importance of non-coding RNAs (ncRNAs) in various diseases, we investigated their roles in glaucoma. Specifically, we detected expression changes of ncRNAs in cell and animal models of acute glaucoma. Further analysis revealed that the Ier2/miR-1839/TSPO axis was critical to cell loss and retinal damage. The knockdown of Ier2, the overexpression of miR-1839, and the silencing of TSPO effectively prevented retinal damage and cell loss. Furthermore, we found that the Ier2/miR-1839/TSPO axis regulated the pyroptosis and apoptosis of retinal neurons through the NLRP3/caspase1/GSDMD, cleaved-caspase3 pathways. In addition to high expression in the retina, TSPO expression was found to be significantly higher in the dorsal lateral geniculate nucleus (DLG) of the brain in the pathologically high intraocular pressure (ph-IOP) rat model, as well as in the peripheral blood mononuclear cells (PBMCs) of glaucoma patients with high IOP. These results indicate that TSPO, which is regulated by Ier2/miR-1839, plays an important role in the pathogenesis of glaucoma, and this study provides a theoretical basis and a new target for the diagnosis and treatment of glaucoma.
Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.

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ABOUT THE EXPERTS

Zhou Zeng,Mengling You,Rong Rong,Cong Fan,Meini Chen,Haibo Li,Dan Ji,Xiaobo Xia

Zhou Zeng

Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Ophthalmology, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.

Mengling You

Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Ophthalmology, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.

Rong Rong

Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Ophthalmology, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.

Cong Fan

Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Ophthalmology, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.

Meini Chen

Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Ophthalmology, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.

Haibo Li

Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Ophthalmology, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.

Dan Ji

Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Ophthalmology, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China. Electronic address: gree1333@csu.edu.cn.

Xiaobo Xia

Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Ophthalmology, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China. Electronic address: xbxia21@csu.edu.cn.