Towards the preclinical diagnosis of diabetic retinopathy and diabetic macular oedema using tear samples

Aims/Purpose: A wide spectrum of molecular‐genetic events, including inflammation (INF), angiogenesis (ANG), apoptosis (AP) and the concurrence of miRNAs and target genes, are involved in diabetic retinopathy (DR) and diabetic macular oedema (DMO). To unravel the complex pathogenesis of DR and DMO, we focus on the microvascular endothelial dysfunction (MVED) pathophysiologic pathways. Methods: Volunteers of both sexes, aged 35–80 years were enrolled and distributed into type 2 diabetics (T2DM), with DR (+DRG; n = 35), without DR (−DRG; n = 35), with DMO (DMOG; n = 28), and controls (CG; n = 40). Sociodemographic and comorbid data, ophthalmologic parameters, and molecular‐genetic variables related to INF, ANG, and AP, assayed in tear samples, were recorded. Statistics were performed by the R Core Team (2022) program. Results: Most of our participants were middle‐aged (mean age was 58 ± 11 years). Differential expression profile in tears was found statistically significant for SOCS6 gene (involved in INF) target of hsa‐miR‐155‐5p, VEGF‐A gene (implicated in ANG) target of hsa‐miR‐15b‐5p, and the BCL2L2 gene (AP effector) target of hsa‐miR‐10a‐5p, in both the +DRG and DMOG, as compared to the −DRG and CG. Conclusions: We confirm that INF, ANG, and AP, regulated by the hsa‐miR‐155‐5p, hsa‐miR‐15b‐5p and hsa‐miR‐10a‐5p, and its respective target genes SOCS6, VEGF‐A, and BCL2L2, expressed in tears, are key players in the development of structural and functional chorioretinal changes associated with MVED in DR/DMO patients. We may propose the above insights as potential diagnostic‐prognostic biomarkers for better managing the diabetic eyes and vision.