Diabetes and other autoimmune endocrine diseases
Diabetes induces chronic-low-grade retinal inflammation that elicits vascular impairment and the development of diabetic retinopathy, which is one of the leading causes of blindness worldwide. Although diabetic retinopathy is predominantly attributed to vascular alterations, recent studies have established a novel role for inflammation and the neural retina in the development of diabetic retinopathy. Here we identified constitutive expression of the IL-17A receptor and the Act1 adaptor molecule on photoreceptors. Further, IL-17A enhanced oxidative stress through a TRAF4 signaling cascade that induced Steap4 expression and reactive oxygen species (ROS) production. Enhanced ROS production leads to capillary degeneration and vascular permeability, which are clinically meaningful abnormalities that characterize the early onset of diabetic retinopathy. These findings identify a novel IL-17A signaling cascade, and potential therapeutic targets that could delay the onset of diabetic retinopathy and vision loss.