The contribution of adiponectin to diabetic retinopathy progression: Association with the AGEs-RAGE pathway
Min Fu,
Li Zhengran,
Li Yingli,
Wu Tong,
Cai Liyang,
Guo Xi,
Yang Xiongyi,
Cao Mingzhe,
Yi Guoguo
Affiliations
Min Fu
Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
Li Zhengran
Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, Guangzhou, China; The Second Clinical School, Southern Medical University, Guangzhou, China
Li Yingli
Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
Wu Tong
Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, Guangzhou, China; The First Clinical School, Southern Medical University, Guangzhou, China
Cai Liyang
Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
Guo Xi
School of Psychological and Cognitive Sciences and Beijing Key Laboratory of Behavior and Mental Health, Peking University, Beijing, China
Yang Xiongyi
Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, Guangzhou, China; The Second Clinical School, Southern Medical University, Guangzhou, China
Cao Mingzhe
Department of Ophthalmology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, 518107, Guangdong Province, China; Corresponding author. Department of Ophthalmology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, 518107, Guangdong Province, China.
Yi Guoguo
Department of Ophthalmology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Corresponding author. Department of Ophthalmology, The Sixth Affiliated Hospital, Sun Yat-sen University, No. 26, Erheng Road, Yuancun, Tianhe, Guangzhou, Guangdong, China.
Diabetic retinopathy (DR) is a chronic complication of diabetes. Given that adiponectin plays a key role in DR progression, this study aims to elucidate the molecular mechanisms of sDR progression related to adiponectin. First, we extracted the microarray dataset GSE60436 from the Gene Expression Omnibus (GEO) database to identify hub genes associated with DR. Pathway enrichment analysis revealed a focus on inflammation, oxidative stress, and metabolic disease pathways. Gene Set Enrichment Analysis (GSEA) identified nine significant pathways related to DR. Immune infiltration analysis indicated increased infiltration of fibroblasts and endothelial cells in DR patients. Second, at the gene level, single-cell RNA sequencing (scRNA-seq) results showed a decrease in ADIPOQ gene expression as the disease progressed in our mouse models. At the protein level, ELISA results from sera of 31 patients and 11 control subjects demonstrated significantly lower adiponectin expression in the proliferative diabetic retinopathy (PDR) group compared to controls. Our findings reveal that adiponectin is involved in the advanced glycation end products (AGEs) and receptor of advanced glycation end products (RAGE) axis, as evidenced by hub gene analysis, scRNA-seq, and ELISA. In conclusion, adiponectin acts as a central molecule in the AGEs-RAGE axis, regulated by ADIPOQ, to influence DR progression.
