Here, we unveil two novel concepts in the pathogenesis of diabetic retinopathy that will further guide us toward rationally-guided new therapies: (i) vasoinhibins can inhibit TRPV4 to maintain BRB and endothelial permeability, (ii) TRPV4 blockage does not seem to contribute to the regulation of BRB and RPE permeability by vasoinhibins under diabetic or hyperglycemic-mimicking conditions; importantly, the TRPV4 antagonist GSK2193874 resolves BRB breakdown associated with diabetes. The gene discussed is TRPV4; the disease is diabetes mellitus.