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Xiangzhe Li, Boram Kang, Youngsub Eom, Jingxiang Zhong, Hyung Keun Lee, Hyo Myung Kim, Jong Suk Song; SIRT1 Protects Against Particulate Matter-Induced Oxidative Stress in Human Corneal and Conjunctival Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2022;63(10):19. doi: https://doi.org/10.1167/iovs.63.10.19.
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Sirtuin1 (SIRT1) as a hot therapeutic target for oxidative stress–associated diseases that has been extensively studied. This study aimed to determine the changes in SIRT1 expression in particulate matter (PM)–induced corneal and conjunctival epithelial cell damage and explore potential drugs to reduce PM-associated ocular surface injury.
Immortalized human corneal epithelial cells (HCECs) and human conjunctival epithelial cells (HCjECs) were exposed to an ambient PM sample. Cytotoxicity was evaluated by water-soluble tetrazolium salt–8 assay. SIRT1 expression was measured by Western blot analysis. Reactive oxygen species (ROS) production, cell apoptosis, mitochondrial function, and cell senescence were assessed by using 2ʹ,7ʹ-dichlorofluorescein diacetate assay, annexin V apoptosis assay, tetramethylrhodamine ethyl ester assay, and senescence β-galactosidase staining, respectively.
PM-induced cytotoxicity of HCECs and HCjECs occurred in a dose-dependent manner. Increased ROS production, as well as decreased SIRT1 expression, were observed in HCECs and HCjECs after 200 µg/mL PM exposure. In addition, PM induced oxidative stress-mediated cellular damage, including cell apoptosis, mitochondrial damage, and cell senescence. Interestingly, SRT1720, a SIRT1 activator, increased SIRT1 expression and decreased ROS production and attenuated PM-induced cell damage in HCECs and HCjECs.
This study determined that SIRT1 was involved in PM-induced oxidative stress in HCECs and HCjECs and found that ROS overproduction may a key factor in PM-induced SIRT1 downregulation. The SIRT1 activator, SRT1720, can effectively upregulate SIRT1 expression and inhibit ROS production, thereby reversing PM-induced cell damage. This study provides a new potential target for clinical treatment of PM-associated ocular surface diseases.
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