Pathogenesis Of IL-17A In Diabetic Retinopathy

Background/Aims:Interleukin(IL)-17A,a proinflammatory cytokine,has been implicated in several autoimmune diseases.However,it is unclear whether IL-17A is involved in diabetic retinopathy(DR),one of the most serious complications of autoimmune diabetes.This study aimed to demonstrate that IL-17A exacerbates DR by affecting retinal Muller cell function.Methods:High glucose(HG)-treated rat Muller cell line(rMC-1)was exposed to IL-17A,anti-IL-17A-neutralizing monoclonal antibody(mAb)or/and anti-IL-17 receptor(R)A-neutralizing mAb for 24 h.For in vivo study,DR was induced by intraperitoneal injections of streptozotocin(STZ).DR model mice were treated with anti-IL-17A mAb or anti-IL-17RA mAb in the vitreous cavity.Mice that wereprepared for retinal angiography were sacrificed two weeks after intravitreal injection,while the rest were sacrificed two days after intravitreal injection.Results:IL-17A production and IL-17RA expression were increased in both HG-treated rMC-1 and DR retina.HG induced rMC-1 activation and dysfunction,as determined by the increased GFAP,VEGF and glutamate levels as well as the downregulated GS and EAAT1 expression.IL-17A exacerbated the HG-induced rMC-1 functional disorders,whereas either anti-IL-17A mAb or anti-IL-17RA mAb alleviated the HG-induced rMC-1 disorders.Intravitreal injections with anti-IL-17A mAb or anti-IL-17RA mAb in DR model mice reduced Muller cell dysfunction,vascular leukostasis,vascular leakage,tight junction protein downregulation and ganglion cell apoptosis in the retina.Conclusions:IL-17A aggravates DR-like pathology at least partly by impairing retinal Muller cell function.Blocking IL-17A is a potential therapeutic strategy for DR.