2. Academic Validation
  3. SRT1720 attenuates UVA-induced corneal endothelial damage via inhibition of oxidative stress and cellular apoptosis

SRT1720 attenuates UVA-induced corneal endothelial damage via inhibition of oxidative stress and cellular apoptosis

  • Exp Eye Res. 2023 Apr 2;109464. doi: 10.1016/j.exer.2023.109464.
Chunxiao Dong 1,  Zongyi Li 2,  Xin Wang 3,  Dulei Zou 1,  Haoyun Duan 2,  Can Zhao 3,  Qingjun Zhou 2,  Weiyun Shi 4
Affiliations

Affiliations

  • 1 Qingdao University, Qingdao, 266071, China; Eye Hospital of Shandong First Medical University (Shandong Eye Hospital), Jinan, 250000, Shandong, China; State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, 266071, China; School of Ophthalmology, Shandong First Medical University, Jinan, 250000, Shandong, China.
  • 2 State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, 266071, China; School of Ophthalmology, Shandong First Medical University, Jinan, 250000, Shandong, China.
  • 3 Eye Hospital of Shandong First Medical University (Shandong Eye Hospital), Jinan, 250000, Shandong, China; State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, 266071, China; School of Ophthalmology, Shandong First Medical University, Jinan, 250000, Shandong, China.
  • 4 Eye Hospital of Shandong First Medical University (Shandong Eye Hospital), Jinan, 250000, Shandong, China; State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, 266071, China; School of Ophthalmology, Shandong First Medical University, Jinan, 250000, Shandong, China. Electronic address: [email protected].
PMID: 37015319 DOI: 10.1016/j.exer.2023.109464
Abstract

Corneal endothelium is mostly sensitive to oxidative pressure and mitochondrial dysfunction. However, the oxidative-antioxidant mechanism of corneal endothelial cells (CECs) remains partially defined. Silent information regulator 1 (SIRT1) is a well-studied therapeutic target of oxidative damage. This study aimed to determine the SIRT1 expression in ultraviolet A (UVA)-induced corneal endothelial damage and explore potential drugs to repair corneal endothelial oxidative injury. In this study, we showed that CECs exhibited cellular Apoptosis, Reactive Oxygen Species (ROS) accumulation and decreased SIRT1 expression. In addition, UVA induced the imbalance of mitochondrial homeostasis and function, involving in mitochondrial membrane potential, mitochondrial fusion/fission and mitochondrial energy metabolism. SRT1720, the SIRT1 Activator, effectively increased SIRT1 expression and attenuated UVA-induced cell damage in CECs. The therapeutic effects of SRT1720 for corneal endothelial oxidative damage were also verified in UVA-irradiated mice model. Our findings indicated that SIRT1 maintained the oxidant-antioxidant balance in corneal endothelium, suggesting a new promising therapeutic target for corneal endothelial dysfunction.

Keywords

Apoptosis; Corneal endothelium; Mitochondrial homeostasis; Oxidate damage; SIRT1; SRT1720.

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