Therapeutic Potential of Mineralocorticoid Receptor Antagonists in Diabetic Retinopathy: Research Progress and Clinical Perspectives

This narrative review evaluates the role of mineralocorticoid receptor (MR) signaling in diabetic retinopathy (DR) and the therapeutic potential and translational limitations of MR antagonists (MRAs). PubMed and ClinicalTrials.gov were searched through August 10, 2026, with priority given to original mechanistic, pharmacokinetic, animal, and human studies. Available evidence indicates that MR activation contributes to retinal inflammation, oxidative stress, vascular leakage, angiogenesis, and Müller-cell ion and water dysregulation. In experimental models, spironolactone and finerenone reduced several pathological retinal endpoints. Finerenone was administered orally at 10 mg/kg/day for 12 weeks in diabetic hypertensive rats and intraperitoneally at 5 mg/kg/day in a mouse model of oxygen-induced retinopathy. In the exploratory ReFineDR/DeFineDR analysis involving 244 participants, the 2-year incidence of vision-threatening complications was 3.7% with finerenone and 6.4% with placebo (difference, -2.6%; 95% confidence interval, -8.2% to 2.9%), while ocular interventions occurred in 3.0% and 15.5% of participants, respectively. However, the ocular subgroup was not separately randomized or powered to evaluate ocular efficacy, and retinal or vitreous concentration-time data following oral finerenone have not been published. MRAs therefore have a biologically plausible and experimentally supported role in retinal disease, but their efficacy for DR in humans remains unproven. Dedicated randomized trials incorporating standardized retinal outcomes, exposure-response assessment, and potassium and kidney function monitoring are warranted.