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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1455439
This article is part of the Research Topic Cellular and Molecular Mechanisms in Metabolic Disorders: Role of Inflammation and Oxidative Stress View all 5 articles

DJ-1 regulates mitochondrial function and promotes retinal ganglion cell survival under high glucose-induced oxidative stress

Provisionally accepted
Hanhan Peng Hanhan Peng Haoyu Li Haoyu Li Benteng Ma Benteng Ma Xinyue Sun Xinyue Sun Baihua Chen Baihua Chen *
  • Second Xiangya Hospital, Central South University, Changsha, China

The final, formatted version of the article will be published soon.

    Purpose: This study aimed to investigate the antioxidative and neuroprotective effects of DJ-1 in mitigating retinal ganglion cell (RGC) damage induced by high glucose (HG). Methods: A diabetic mouse model and an HG-induced R28 cell model were employed for loss- and gain-of-function experiments. The expression levels of apoptosis and oxidative stress-related factors, including Bax, Bcl-2, caspase3, Catalase, MnSOD, GCLC, Cyto c, and GPx-1/2, were assessed in both animal and cell models using western blotting. Retinal structure and function were evaluated through HE staining, electroretinogram, and RGC counting. Mitochondrial function and apoptosis were determined using JC-1 and TUNEL staining, and reactive oxygen species (ROS) measurement. Results: In the mouse model, hyperglycemia resulted in reduced retinal DJ-1 expression, retinal structural and functional damage, disrupted redox protein profiles, and mitochondrial dysfunction. Elevated glucose levels induced mitochondrial impairment, ROS generation, abnormal protein expression, and apoptosis in R28 cells. Augmenting DJ-1 expression demonstrated a restoration of mitochondrial homeostasis and alleviated diabetes-induced morphological and functional impairments both in vivo and in vitro. Conclusion: This study provides novel insights into the regulatory role of DJ-1 in mitochondrial dynamics, suggesting a potential avenue for enhancing RGC survival in diabetic retinopathy.

    Keywords: Diabetic Retinopathy, Retinal Ganglion Cells, Mitochondria, Oxidative Stress, DJ-1

    Received: 26 Jun 2024; Accepted: 02 Sep 2024.

    Copyright: © 2024 Peng, Li, Ma, Sun and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Baihua Chen, Second Xiangya Hospital, Central South University, Changsha, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.