New Gene Targets for Diagnosis and Therapy of Diabetic Retinopathy

Objective: Diabetic retinopathy (DR), considered one of the most common microvascular complications associated with diabetes mellitus (DM), involves both neuronal and vascular dysfunctions in the retina. Neuronal damage and vision loss occur progressively in patients with DR. A number of genetic targets have been identified for DR and gene-related treatments as well as early diagnostic techniques have been developed. Despite some medical advances, DR remains a devastating complication of diabetes. This study aimed to identify new gene targets that can be used for the prognosis and treatment of DR.. Materials and Methods: Eight candidate genes were analyzed using Synergy Brands Green (SYBR-green)- based real-time polymerase chain reaction in peripheral blood mononuclear cells (PBMCs) from 45 individuals: DR patients (n=15), DM patients without DR (n=15), and healthy controls (n=15). STRING v11 was used for protein-protein interaction analysis. Gene expression differences were evaluated using ANOVA, with significance set at P < .05. Results: HIF1A and VEGFA were significantly upregulated in both DR and DM groups compared to controls (HIF1A: fold change 5.28; VEGFA: fold change 5.20 for DR group). SERPING1 was specifically upregulated in DR patients (fold change 3.42). CX3CR1 and BDNF were downregulated in both DR and DM groups (CX3CR1: fold change 8.32; BDNF: fold change 3.21), while IGFBP3 was significantly downregulated only in DR patients (fold change 6.5). STRING analysis revealed strong interactions between SERPING1 and complement pathway components, while IGFBP3 was linked to insulin-like growth factor signaling. Conclusion: In light of these findings, we observed that SERPING1 and IGFBP3 genes might be proposed as targets for early diagnosis and treatment for DR.