Multi-omics analysis of potential metabolic networks linking peripheral metabolic changes to inflammatory retinal conditions in STZ-induced early diabetic retinopathy
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 stre...
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Elsevier
2025-09-01
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| Series: | Biochemistry and Biophysics Reports |
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| author | Xiaonan Zhang Yan Liu Mengxue Xia Manwen Yang Yingjie Wu Fang Zhang |
| author_facet | Xiaonan Zhang Yan Liu Mengxue Xia Manwen Yang Yingjie Wu Fang Zhang |
| author_sort | Xiaonan Zhang |
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| description | 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 of peripheral serum metabolites associated with early retinal lesions. Specifically, the SNPs in key peripheral enzyme genes may exert remote effects on retinal inflammation in DR. This finding provides insights into the systemic metabolic management and offering peripheral precise early detection and treatment. |
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| institution | Kabale University |
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| language | English |
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| spelling | doaj-art-90fd6866c955464f89096ae4d64ad4652025-08-24T05:13:28ZengElsevierBiochemistry and Biophysics Reports2405-58082025-09-014310218210.1016/j.bbrep.2025.102182Multi-omics analysis of potential metabolic networks linking peripheral metabolic changes to inflammatory retinal conditions in STZ-induced early diabetic retinopathyXiaonan Zhang0Yan Liu1Mengxue Xia2Manwen Yang3Yingjie Wu4Fang Zhang5National Clinical Research Center for Eye disease, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; Liaoning Provence Key Laboratory of Genome Engineered Animal Models, National Center of Genetically Engineered Animal Models for International Research, Institute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian 116000, China; Eye Institute of Shanghai Jiao Tong University School, Shanghai 200080, ChinaNational Clinical Research Center for Eye disease, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; Liaoning Provence Key Laboratory of Genome Engineered Animal Models, National Center of Genetically Engineered Animal Models for International Research, Institute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian 116000, China; Eye Institute of Shanghai Jiao Tong University School, Shanghai 200080, ChinaNational Clinical Research Center for Eye disease, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; Eye Institute of Shanghai Jiao Tong University School, Shanghai 200080, China; Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai 200080, ChinaNational Clinical Research Center for Eye disease, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; Eye Institute of Shanghai Jiao Tong University School, Shanghai 200080, China; Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai 200080, ChinaLiaoning Provence Key Laboratory of Genome Engineered Animal Models, National Center of Genetically Engineered Animal Models for International Research, Institute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian 116000, China; Shandong Provincial Hospital, School of Laboratory Animal & Shandong Laboratory Animal Center, Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250021, China; Department of Molecular Pathobiology, New York University College of Dentistry, New York, NY 10010, USA; Corresponding author.Liaoning Provence Key Laboratory of Genome Engineered Animal Models, National Center of Genetically Engineered Animal Models for International Research, Institute for Genome Engineered Animal Models of Human Diseases, Dalian Medical University, Dalian 116000, China.National Clinical Research Center for Eye disease, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; Eye Institute of Shanghai Jiao Tong University School, Shanghai 200080, China; Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai 200080, China; Corresponding author.National Clinical Research Center for Eye disease, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.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 of peripheral serum metabolites associated with early retinal lesions. Specifically, the SNPs in key peripheral enzyme genes may exert remote effects on retinal inflammation in DR. This finding provides insights into the systemic metabolic management and offering peripheral precise early detection and treatment.http://www.sciencedirect.com/science/article/pii/S2405580825002699Diabetic retinopathyRetinaSerumMetabolomicsTranscriptomicsGWAS |
| spellingShingle | Xiaonan Zhang Yan Liu Mengxue Xia Manwen Yang Yingjie Wu Fang Zhang Multi-omics analysis of potential metabolic networks linking peripheral metabolic changes to inflammatory retinal conditions in STZ-induced early diabetic retinopathy Biochemistry and Biophysics Reports Diabetic retinopathy Retina Serum Metabolomics Transcriptomics GWAS |
| title | Multi-omics analysis of potential metabolic networks linking peripheral metabolic changes to inflammatory retinal conditions in STZ-induced early diabetic retinopathy |
| title_full | Multi-omics analysis of potential metabolic networks linking peripheral metabolic changes to inflammatory retinal conditions in STZ-induced early diabetic retinopathy |
| title_fullStr | Multi-omics analysis of potential metabolic networks linking peripheral metabolic changes to inflammatory retinal conditions in STZ-induced early diabetic retinopathy |
| title_full_unstemmed | Multi-omics analysis of potential metabolic networks linking peripheral metabolic changes to inflammatory retinal conditions in STZ-induced early diabetic retinopathy |
| title_short | Multi-omics analysis of potential metabolic networks linking peripheral metabolic changes to inflammatory retinal conditions in STZ-induced early diabetic retinopathy |
| title_sort | multi omics analysis of potential metabolic networks linking peripheral metabolic changes to inflammatory retinal conditions in stz induced early diabetic retinopathy |
| topic | Diabetic retinopathy Retina Serum Metabolomics Transcriptomics GWAS |
| url | http://www.sciencedirect.com/science/article/pii/S2405580825002699 |
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