Molecular Hydrogen Attenuated N-methyl-N-Nitrosourea Induced Corneal Endothelial Injury by Upregulating Anti-Apoptotic Pathway

Runpu Li, Yingxin Qu, Xiaoqi Li, Ye Tao, Qinghua Yang, Junyi Wang, Yumei Diao, Qian Li, Yifan Fang, Yifei Huang, Liqiang Wang

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DOI: 10.1167/iovs.62.9.2 DOI is the universal ID for this study.

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Abstract:

Purpose: Previous work by our group has demonstrated the value of N-methyl-N-nitrosourea (MNU)-induced corneal endothelial decompensation in animal models. The aim of this study was to investigate the effect of molecular hydrogen (H2) on MNU-induced corneal endothelial cell (CEC) injury and the underlying mechanism.

Methods: MNU-induced animal models of CEC injury were washed with hydrogen-rich saline (HRS) for 14 days. Immunofluorescence staining, immunohistochemical staining, and corneal endothelial assessment were applied to determine architectural and cellular changes on the corneal endothelium following HRS treatment. MNU-induced cell models of CEC injury were co-cultured with H2. The effect of H2 was examined using morphological and functional assays.

Results: It was shown that MNU could inhibit the proliferation and specific physiological functions of CECs by increasing apoptosis and decreasing the expression of ZO-1 and Na+/K+-ATPase, whereas H2 improved the proliferation and physiological function of CECs by anti-apoptosis. Cell experiments further confirmed that H2 could reverse MNU damage to CECs by decreasing oxidative stress injury, interfering with the NF-κB/NLRP3 pathway and the FOXO3a/p53/p21 pathway. Conclusions: This study suggests that topical application of H2 could protect CECs against corneal damage factors through anti-apoptotic effect, reduce the incidence and severity of corneal endothelial decompensation, and maintain corneal transparency.


Publish Year 2021
Country China
Rank Positive
Journal Investigative Ophthalmology and Visual Science
Primary Topic Eye
Secondary Topic Corneal Injury
Model Rabbit
Tertiary Topic Cataract
Vehicle Saline (Dissolved)
pH Neutral
Application Irrigation
Comparison
Complement