Diabetes and other autoimmune endocrine diseases
Diabetic retinopathy is a diabetes-mediated retinal microvascular disease, and is the leading cause of blindness in the working-age population in the Western World. Interleukin-17A (IL-17A) and matrix metallopeptidase 9 (MMP-9) have both been identified as key inflammatory processes that induce retinal pathogenesis and the onset of diabetic retinopathy. Here the role of IL-17A in the production and activation of MMP-9 in retina, as wells as the signaling mechanism that enhances MMP-9 activity was investigated. It was discovered that diabetes-mediated MMP-9 production and activity was significantly decreased in IL17A-/- STZ-diabetic mice. Also through ex vivo studies of human retina cells, it was determined that IL-17A induced IL-17-receptor-expressing Muller glia to produce MMP-9 by activating the IL-17R-Act1-TRAF6 pathway. These findings not only establish a novel IL-17A signaling mechanism in the retina, but also identify potential therapeutic targets that could inhibit retinal pathogenesis and the development of diabetic retinopathy.