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Multi-omics analysis of potential metabolic networks linking peripheral metabolic changes to inflammatory retinal

Xiaonan Zhang1,2,3, Yan Liu1,2,3, Mengxue Xia1,3,4

  • 1National Clinical Research Center for Eye disease, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.

Biochemistry and Biophysics Reports
|September 12, 2025
PubMed
Abstract

Insights

Diabetic retinopathy (DR) involves retinal inflammation linked to serum metabolites. Genetic variations in key metabolic enzymes may remotely influence DR, suggesting new avenues for systemic metabolic management and early detection.

Area of Science:

  • Ophthalmology
  • Metabolomics
  • Genetics

Background:

  • Diabetic retinopathy (DR) is a major cause of blindness.
  • Current treatments focus on glucose control, lacking targeted therapies for early lesions.
  • The peripheral metabolic networks influencing early DR remain unclear.

Purpose of the Study:

  • To investigate the upstream regulatory network of peripheral serum metabolites associated with early retinal lesions in diabetic retinopathy.
  • To identify potential peripheral biomarkers and therapeutic targets for DR.

Main Methods:

  • Established a streptozotocin (STZ)-induced mouse model of early DR.
  • Integrated retinal and serum transcriptomic and metabolomic data with genome-wide association study (GWAS) data.
  • Analyzed alterations in key metabolic pathways and identified correlations between gene polymorphisms and metabolites.

Main Results:

  • STZ-induced mice showed retinal inflammation and metabolic dysregulation, with altered glucose, sorbitol, and mannitol levels.
  • GWAS data revealed that single nucleotide polymorphisms (SNPs) in key enzyme genes (e.g., HK1, AKR1B1, CEL, HMGCR, ACSL1) may link peripheral metabolic changes to retinal inflammation.
  • Identified potential connections between hyperglycemia, hyperfructosemia, disrupted lipid metabolism, and retinopathy.

Conclusions:

  • Elucidated the upstream regulatory network of peripheral metabolites in early DR.
  • Demonstrated that SNPs in peripheral enzyme genes may remotely affect retinal inflammation in DR.
  • Findings support systemic metabolic management and precise peripheral early detection and treatment strategies for DR.
Keywords:
Diabetic retinopathyGWASMetabolomicsRetinaSerumTranscriptomics

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