ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Diabetes: Molecular Mechanisms
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1652898
This article is part of the Research TopicMitochondrial Dynamics and Endothelial Dysfunction: Implications for Metabolic DisordersView all 4 articles
Identification and Validation of Key Mitophagy-Related Biomarkers in the Pathogenesis of Proliferative Diabetic Retinopathy
Provisionally accepted
Yifan Liu1Ye Zhou1Jie Chen1Jiahui Jin1Xueying Wang1Xi Wang1
Jieping Zhang1
Jiao Li1Junfang Zhang1Ling Zhu1Guo-Tong Xu1
Yanlong Bi1
Qingjian Ou1,2*
Caixia Jin1- 1Tongji University School of Medicine, Shanghai, China
- 2Tongji University, Shanghai, China
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Abstract Introduction: Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes mellitus, and proliferative diabetic retinopathy (PDR) represents its advanced stage. The etiology of PDR is complex. Mitophagy, the selective degradation of dysfunctional mitochondria, is crucial for cellular homeostasis and has been implicated in PDR pathogenesis. However, its specific mechanisms require further investigation. Materials and Methods: Gene Expression Omnibu (GEO) datasets (GSE102485, GSE60436) were analyzed in R software to identify differentially expressed mitophagy-related genes (DEMRGs). A PDR diagnostic model was constructed by gene ontology (GO) enrichment analysis, genome enrichment analysis (GSEA), and other relevant methods. Immune infiltration was also performed to analyze the changes in immune cells. Finally, the retinal pigment epithelial cell line (ARPE-19) was incubated with high glucose (HG) to simulate a DR model in vitro, hub-gene expression and mitophagy were assessed by qRT-PCR, Western blotting, and immunofluorescence microscopy (IF). Results: Eight DEMRGs were identified enabling construction of a PDR diagnostic model and prioritization of two hub genes (CASP8 and COL1A1). Finally, qRT-PCR, Western blotting, and IF were performed to provide preliminary validation of the PDR model and HG stimulation increased mitochondria–lysosome colocalization as well as enhanced the expression of mitophagy-related proteins. Discussion: Integrated bioinformatics and experimental validation suggest that mitophagy contributes to PDR pathogenesis. Five DEMRGs showed up-regulated and immune cell infiltration that may affect the occurrence and PDR development by regulating mitophagy. These findings provide candidate biomarkers and mechanistic insight into PDR.
Keywords: proliferative diabetic retinopathy, mitophagy, Differentially expressed genes, CASP8, COL1A1
Received: 24 Jun 2025; Accepted: 13 Oct 2025.
Copyright: © 2025 Liu, Zhou, Chen, Jin, Wang, Wang, Zhang, Li, Zhang, Zhu, Xu, Bi, Ou and Jin. 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: Qingjian Ou, vip@ouqingjian.com
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