Omae_2025_Invest.Ophthalmol.Vis.Sci_66_4

PURPOSE: The study objective was to examine the role of dipeptidyl peptidase 4 (DPP4) on retinal microcirculation in patients with type 2 diabetes mellitus (DM) and an in vitro study. METHODS: Sixty-seven patients with type 2 diabetes and minimal diabetic retinopathy (DR) were divided into two groups based on gender. We compared the patients' retinal circulatory parameters measured with laser Doppler velocimetry and serum DPP4 concentrations. Using isolated retinal arterioles, we also compared the retinal endothelial function before and after DPP4 incubation. RESULTS: The plasma DPP4 concentrations were correlated negatively with the retinal vessel diameter (D) and retinal blood flow (RBF) in men but not women. Multiple regression analysis showed that the plasma DPP4 level was independently and negatively correlated with the vessel D. In vitro, intraluminal DPP4 treatment significantly attenuated endothelium-dependent nitric oxide (NO)-mediated vasodilation with a dose-dependent manner. Superoxide scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), the NADPH oxidase inhibitor apocynin, and the DPP4 inhibitor teneligliptin, prevented the retinal endothelial dysfunction induced by DPP4. CONCLUSIONS: Our results indicated that high serum DPP4 concentration may be associated with decreased RBF, probably via the constricted vessel D in men with type 2 diabetes with early-phase DR and further that DPP4 may inhibit endothelium-dependent NO-mediated dilation in the retinal arterioles via producing superoxide from NADPH oxidase.