The role of IL-17A in the onset and progression of diabetic retinopathy in VA patients

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Abstract Currently, 9% of the US population is diabetic, and an additional 86 million are being treated for pre-diabetes. Beyond this, one in every four Veteran receiving care from the VA is being treated for diabetes and its many physical complications, with more than half suffering from diabetic retinopathy. Making diabetic retinopathy a disease with a high healthcare burden in the Veteran population. Diabetic retinopathy is a microvascular disease of the retina, and is the leading cause of blindness in the working-age population worldwide. With such a significant health impact, new therapeutics is required to stay abreast of the financial and physical threat posed by this visual disease. One of the most promising sources of such a therapeutic target lies within the immune system. The alteration of the immune system mediates much of the pathogenesis in diabetic complications through protein cytokine production, with IL-17A being one of the most prevalent cytokines involved in the onset and progression of diabetes. In our previous studies, we discovered that diabetes induced IL-17A production, which enhanced retinal inflammation, oxidative stress, vascular impairment, and the onset of non-proliferative diabetic retinopathy in murine models of diabetes. In the current study we will examine if IL-17A plays the same pathologic role in the progression of non-proliferative diabetic retinopathy, proliferative diabetic retinopathy, and diabetic macular edema in our VA patients. Further, previous cancer studies provide evidence that IL-17A induces anti-VEGF drug resistance. Here we will examine if IL-17A plays the same role in patients that do not respond to anti-VEGF treatments for diabetic retinopathy. Taken together, these studies will define the role of IL-17A in the onset and progression of diabetic retinopathy, while potentially identifying a novel therapeutic for retinal pathogenesis.