Circulating microRNAs as diagnostic biomarkers and pathogenic mediators in type 2 diabetic retinopathy: a systematic review.

Abstract

Background: This systematic review synthesizes current evidence on circulating microRNAs (miRNAs) associated with diabetic retinopathy (DR) in individuals with type 2 diabetes (T2D). DR is a leading cause of vision impairment among adults with diabetes. Identifying circulating miRNAs as minimally invasive biomarkers could enable early DR detection, improve disease monitoring, and support therapeutic development.

Methods: Following PRISMA guidelines, PubMed and Scopus were systematically searched for English-language studies published between January 2014 and 20 July 2024. Observational studies reporting quantitative expression data (fold-change) of circulating miRNAs in serum or plasma samples from patients with DR and T2D controls were included. Data extraction and quality assessment were independently performed by two reviewers.

Results: From 957 screened records, 16 studies met all inclusion criteria. Most studies were conducted in Chinese cohorts and collectively identified numerous differentially expressed miRNAs implicated in NF-κB signaling, PI3K/Akt signaling, angiogenesis, and neuronal apoptosis. Several miRNAs, including hsa-miR-155, hsa-miR-320a, hsa-miR-320b and hsa-miR-338-3p showed consistent dysregulation across multiple studies and demonstrated promise as non-invasive biomarkers for DR diagnosis and progression monitoring. However, heterogeneity in study design, small sample sizes, and limited validation experiments reduced comparability across studies.

Conclusion: Current evidence supports the potential of circulating miRNAs as biomarkers for early detection and monitoring of DR in T2D. Nevertheless, larger, multiethnic, and longitudinal studies with standardized protocols, coupled with mechanistic and functional validation, are essential to confirm their diagnostic and therapeutic utility.