Diabetic retinopathy is a prevailing diabetes complication, and one of the leading causes of blindness worldwide. IL-17A is a cytokine involved in the onset of diabetic complications. In the current study, we examined the role of IL-17A in the development of retinal inflammation and long-term vascular pathology in diabetic mice. We found IL-17A expressing T cells and neutrophils in the retinal vasculature. Further, the IL-17A receptor was expressed on Muller glia, retinal endothelial cells, and photoreceptors. Finally, diabetes-mediated retinal inflammation, oxidative stress, and vascular leakage were all significantly lower in IL-17A −/− mice. These are all clinically meaningful abnormalities that characterize the onset of diabetic retinopathy.

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Diabetic retinopathy is a diabetes-mediated retinal microvascular disease that is the leading cause of blindness in the working-age population worldwide. Interleukin (IL)-17A is an inflammatory cytokine that has been previously shown to play a pivotal role in the promotion and progression of diabetic retinopathy. Retinoic acid-related orphan receptor gammaT (RORγt) is a ligand-dependent transcription factor that mediates IL-17A production. However, the role of RORγt in diabetes-mediated retinal inflammation and capillary degeneration, as well as its potential therapeutic attributes for diabetic retinopathy has not yet been determined. In the current study, we examined retinal inflammation and vascular pathology in streptozotocin-induced diabetic mice. We found RORγt expressing cells in the retinal vasculature of diabetic mice. Further, diabetes-mediated retinal inflammation, oxidative stress, and retinal endothelial cell death were all significantly lower in RORγt−/− mice. Finally, when a RORγt small molecule inhibitor (SR1001) was subcutaneously injected into diabetic mice, retinal inflammation and capillary degeneration were ameliorated. These findings establish a pathologic role for RORγt in the onset of diabetic retinopathy and identify a potentially novel therapeutic for this blinding disease.