Du XL, Ouyang S, Wang YS, Mao YS, Ren BC, Yu WH. PRDX2 silencing alleviates reactive hyperplasia of Müller glial cells in diabetic retinopathy by inhibiting the RhoA/ROCK signaling pathway. World J Diabetes 2026; 17(3): 115433 [DOI: 10.4239/wjd.v17.i3.115433]
Corresponding Author of This Article
Wei-Hong Yu, MD, PhD, Professor, Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan Wangfujing, Dongcheng District, Beijing 100730, China. yuweihongpumch@163.com
Research Domain of This Article
Endocrinology & Metabolism
Article-Type of This Article
Basic Study
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Mar 15, 2026 (publication date) through Mar 15, 2026
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Journal Information of This Article
Publication Name
World Journal of Diabetes
ISSN
1948-9358
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Du XL, Ouyang S, Wang YS, Mao YS, Ren BC, Yu WH. PRDX2 silencing alleviates reactive hyperplasia of Müller glial cells in diabetic retinopathy by inhibiting the RhoA/ROCK signaling pathway. World J Diabetes 2026; 17(3): 115433 [DOI: 10.4239/wjd.v17.i3.115433]
Xiao-Lan Du, Shuai Ouyang, Yu-Song Wang, Yi-Shuang Mao, Bei-Cheng Ren, Wei-Hong Yu, Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Xiao-Lan Du, Shuai Ouyang, Yu-Song Wang, Yi-Shuang Mao, Bei-Cheng Ren, Wei-Hong Yu, Key Laboratory of Ocular Fundus Diseases, Chinese Academy of Medical Sciences, Beijing 100730, China
Xiao-Lan Du, Shuai Ouyang, Yu-Song Wang, Yi-Shuang Mao, Bei-Cheng Ren, Wei-Hong Yu, Key Laboratory of Fundus Diseases Intelligent Diagnosis & Drug/Device Development and Translation, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Co-first authors: Xiao-Lan Du and Shuai Ouyang.
Author contributions: Du XL and Ouyang S contribute equally to this study as co-first authors; Yu WH and Du XL conceptualized and designed the study; Yu WH and Wang YS performed supervision and project administration; Du XL, Ouyang S, Wang YS, Mao YS, and Ren BC collected the data, performed statistical analysis, and drafted the manuscript; Du XL and Ouyang S revised the manuscript; all authors read and approved the final version of the manuscript.
Institutional review board statement: The study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of Peking Union Medical College Hospital (Approval No. JS-3253).
Conflict-of-interest statement: No potential conflict of interest relevant to this article was reported.
Data sharing statement: Upon reasonable request, the datasets generated and analyzed in this study are available from the corresponding or first author.
Corresponding author: Wei-Hong Yu, MD, PhD, Professor, Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan Wangfujing, Dongcheng District, Beijing 100730, China. yuweihongpumch@163.com
Received: October 22, 2025 Revised: December 26, 2025 Accepted: January 22, 2026 Published online: March 15, 2026 Processing time: 142 Days and 3.7 Hours
Abstract
BACKGROUND
Diabetic retinopathy (DR) is a leading cause of adult blindness and involves Müller cell dysfunction, which contributes to neurovascular damage in the retina. PRDX2, a member of the thioredoxin family, possesses antioxidant properties and plays roles in cell survival and vascular remodeling. It also exhibits proinflammatory effects in diabetic nephropathy. However, its specific role in the pathogenesis of DR, particularly in relation to Müller cells, remains poorly understood.
AIM
To investigate the role of PRDX2 in DR progression and to elucidate its mechanism in regulating high-glucose (HG)-induced reactive hyperplasia of Müller cells.
METHODS
A case-control study involving 220 participants (47 healthy controls and 173 individuals with diabetes) was conducted to evaluate plasma PRDX2 levels. Ocular PRDX2 expression was analyzed using vitreous humor samples from proliferative DR (PDR) patients, retinal tissues from DR patients (GSE53257), and retinas from streptozotocin (STZ)-induced diabetic mice (GSE178121). In vitro, PRDX2-knockdown rMC-1 cells (a rat Müller glial cell line) exposed to HG conditions were used to assess the role of PRDX2 in HG-induced gliosis through functional and molecular analyses.
RESULTS
Plasma PRDX2 levels were positively correlated with DR severity (r = 0.267, P < 0.0001) and independently predicted PDR risk after adjustment for confounding factors, including hypertension, age, serum creatinine, urea, fasting blood glucose, and vascular endothelial growth factor A levels (cut-off > 124.3 pg/mL; adjusted odds ratio = 9.097; 95% confidence interval: 2.819-29.355; P = 0.0002). In alignment with its systemic elevation, PRDX2 was markedly upregulated in vitreous humor of PDR patients, retinas of DR patients (GSE53257), Müller cells from STZ-induced diabetic mice (GSE178121), and HG-treated rMC-1 cells. PRDX2 silencing attenuated HG-induced Müller cell hyperproliferation and reduced nestin expression, a marker of gliosis. Mechanistically, this effect was mediated through upregulation of RhoGDI1 and suppression of the RhoA/ROCK signaling pathway, as demonstrated by quantitative proteomics and western blot analysis.
CONCLUSION
PRDX2 promotes Müller cell gliosis in DR via the RhoGDI1-RhoA/ROCK axis, making it a potential biomarker and therapeutic target.
Core Tip: This study identifies PRDX2 as a potential biomarker and mechanistic contributor in diabetic retinopathy (DR). PRDX2 was upregulated in both patient plasma and ocular tissues, with plasma levels showing a positive correlation with disease severity and serving as a significant predictor of proliferative DR. In vitro, PRDX2 silencing mitigated high-glucose-induced reactive hyperplasia in rat Müller cells. This effect was mediated by upregulation of RhoGDI1 and suppression of the downstream RhoA/ROCK signaling pathway. Targeting the PRDX2-RhoGDI1-RhoA axis may offer a novel therapeutic approach for alleviating neuroglial dysfunction in DR pathogenesis.
