Multi-omics analysis of potential metabolic networks linking peripheral metabolic changes to inflammatory retinal conditions in STZ-induced early diabetic retinopathy

作者：Xiaonan Zhang, Yan Liu, Mengxue Xia, Manwen Yang, Yingjie Wu, Fang Zhang · 发表于：Biochemistry and Biophysics Reports · 年份：2025 · DOI：10.1016/j.bbrep.2025.102182 · 被引用次数：3 · 研究领域：Retinal Diseases and Treatments、Aldose Reductase and Taurine、Metabolomics and Mass Spectrometry Studies

Background: Diabetic retinopathy (DR), a leading cause of blindness among working-age adults, lacks targeted therapies besides glucose management. Early retinal lesions are linked to serum metabolites, but the underlying peripheral regulatory networks is unclear. Methods: We first established a streptozotocin (STZ)-induced mouse model of early DR exhibiting retinal inflammation characteristics. This study employed an integrative approach, combining retinal and serum transcriptomic and metabolomic profiles with genome-wide association study (GWAS) data, to identify peripheral metabolites potentially linking early retinal lesions. Results: STZ-induced mice exhibited retinal inflammation and metabolic dysregulation. Metabolites including glucose, sorbitol, and mannitol were altered in both serum and retina, implicating their potential involvement in retinal inflammation. Utilizing GWAS data of diabetic patients, we further explore the potential the upstream regulation of shared metabolites and their peripheral pathways potentially instigating early retinal inflammation through metabolite-related genes correlated with single nucleotide polymorphisms. Key enzyme genes including HK1, HKDC1, AKR1B1 in hyperglycemic pathway, CEL and HMGCR in cholesterol pathway, and ACSL1, PPT2 in palmitic acid pathway, may connect the metabolic network of hyperglycemia, hyperfructosemia and disrupted lipid metabolism to retinopathy. Conclusion: This study elucidates the upstream regulatory network o...