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Type 2 Diabetes Mellitus Makes Corneal Endothelial Cells Vulnerable to Ultraviolet A-Induced Oxidative Damage Via Decreased DJ-1/Nrf2/NQO1 Pathway.


ABSTRACT:

Purpose

The purpose of this study was to investigate whether type 2 diabetes mellitus (T2DM) makes corneal endothelial cells (CECs) suffer from more severe ultraviolet A (UVA)-induced oxidative damage and explore its mechanisms via measuring the oxidant level and the antioxidant level in vitro.

Methods

Corneas of spontaneous T2DM db/db mice and non-diabetes littermate control mice were irradiated with UVA, leading to oxidative damage of CECs. Anterior segment-optical coherence tomography, corneal image, and CECs immunohistochemistry staining were taken thereafter to measure central corneal thickness, corneal edema degree, and damage extent of CECs. In vitro, human corneal endothelial cells line B4G12 (HCECs) treated with high glucose (HG) and low glucose (LG) were exposed to UVA light separately. Subsequently, cellular proliferation, apoptosis, pro-oxidant factors, such as reactive oxygen species (ROS), antioxidant factors including Parkinson's disease protein 7 (DJ-1), nuclear factor-erythroid 2 related factor 2 (Nrf2), phosphorylated-Nrf2, and NAD(P)H: quinone oxidoreductase 1 (NQO1) were measured.

Results

T2DM mice presented greater oxidant damage of CECs and more distinct corneal edema compared with control mice when they were irradiated with the 150 J/cm2 UVA light. In vitro, HCECs in HG condition showed a significant decrease of proliferation, higher apoptosis extent, more ROS generation, lower expressions of DJ-1/Nrf2/NQO1, and distinct reduction of Nrf2 nuclear translocation compared to those in LG condition after exposing to 5 J/cm2 UVA light.

Conclusions

Increase of ROS, downregulation of DJ-1/Nrf2/NQO1 expressions, and decrease of Nrf2 nuclear translocation could result in that T2DM makes CECs more vulnerable to oxidative damage.

SUBMITTER: Zhang X 

PROVIDER: S-EPMC9680587 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

Type 2 Diabetes Mellitus Makes Corneal Endothelial Cells Vulnerable to Ultraviolet A-Induced Oxidative Damage Via Decreased DJ-1/Nrf2/NQO1 Pathway.

Zhang Xueling X   Qiu Jini J   Huang Feifei F   Shan Kun K   Zhang Chaoran C  

Investigative ophthalmology & visual science 20221101 12


<h4>Purpose</h4>The purpose of this study was to investigate whether type 2 diabetes mellitus (T2DM) makes corneal endothelial cells (CECs) suffer from more severe ultraviolet A (UVA)-induced oxidative damage and explore its mechanisms via measuring the oxidant level and the antioxidant level in vitro.<h4>Methods</h4>Corneas of spontaneous T2DM db/db mice and non-diabetes littermate control mice were irradiated with UVA, leading to oxidative damage of CECs. Anterior segment-optical coherence tom  ...[more]

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