Highly-Expressed MiR-221-3p Distinctly Increases the Incidence of Diabetic Retinopathy in Patients With Type 2 Diabetes Mellitus.

Objective: Diabetic retinopathy (DR) is the leading cause of blindness in patients with diabetes mellitus (DM). MiR-221-3p is implicated in microvascular dysfunction in DR, and we explored their relationship. Methods: Patients with type 2 diabetes mellitus (T2DM) were allocated to the non-DR (NDR)/nonproliferative DR (NPDR)/proliferative DR (PDR) groups, with their clinical baseline and pathological data collected. The miR-221-3p and VEGF levels were determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and ELISA, respectively. Peripheral blood endothelial progenitor cell (EPC) and endothelial cell (EC) ratios were ascertained by flow cytometry. The correlations between miR-221-3p levels and VEGF/EPCs/ECs, the predictive value of serum miR-221-3p levels in DR, and the independent risk factors for DR occurrence in T2DM were analyzed by Pearson's correlation analysis, receiver operating characteristic (ROC) curve, and multifactorial logistic regression analysis. Results: Serum miR-221-3p was highly expressed in DR. Clinical severity of DR was positively correlated with miR-221-3p levels. Endothelial function was impaired in DR. Serum miR-221-3p levels in DR were favorably correlated with VEGF and ECs and negatively associated with EPCs. The area under the curve of serum miR-221-3p in evaluating DR occurrence in patients with T2DM was 0.8178 (1.235 cutoff value, 69.62% sensitivity, and 82.35% specificity). High expression of miR-221-3p increased DR incidence in patients with T2DM. Diabetes course, VEGF, EPCs, ECs, and miR-221-3p levels were independent risk factors for DR development in patients with T2DM. Conclusions: Serum miR-221-3p levels in patients with DR were positively correlated with VEGF and ECs and negatively linked with EPCs. Highly expressed miR-221-3p distinctly increased DR incidence in patients with T2DM and was an independent risk factor for DR development in patients with T2DM. Translational Relevance: This study assessed serum miR-221-3p level and endothelial function indicators (VEGF, EPCs, and ECs) in patients with DR and analyzed the correlation between each indicator. We found that high serum miR-221-3p expression prominently increased the incidence of DR in patients with T2DM and was an independent risk factor for the development of DR in patients with T2DM. This study provided a scientific basis for further clarification of the pathogenesis of DR, and also provided new ideas for clinical prediction and management of DR.