The Role Of TLR3in The Pathogenesis Of Diabetic Retinopathy

Purpose:We detect the level of TLR3expression in early retina of diabetic rats,as well as effects on rat retinal damage degree of its ligand poly (I: C) toevaluate the role of TLR3in the pathogenesis of diabetic retinopathy.Methods:Healthy SD rats, male, were divided into two groups, normal controlgroup (CN) and diabetes group(DM). We implement streptozotocin (STZ)intraperitoneal injection to induce the diabetes mellitus (DM) rats models.The DM rats were sacrificed after4weeks. Gene expression of TLR3andinflammatory cytokines IL-6、IL-1α、TNF-α were detected by real-timePCR; Expression of TLR3protein was observed by immunohistochemicalstaining.Polyinosinic:polycytidylic acid (poly(I:C)), a synthetic mimic of viraldsRNA, was administrated intravitreal injection to normal and DM rats.48hours later, retinas were collected and TLR3protein expression wasdetected by Western Blot; TLR3, IL-6、IL-1α、TNF-α mRNA expression were detected by real-time PCR.Results:TLR3and IL-6、IL-1α、TNF-α expression were significantly increasedin diabetic rats retina compared to normal SD rats,(P <0.05). Vitreouscavity local treatment with poly(I:C) can significant up-regulate TLR3,IL-6, IL-1α and TNF-α expression in the retina of rat from normal and DMgroups (P <0.05). HE staining of retina demonstrates that the DM rats withpoly (I: C) intervention had a significantly retinal edema and damagecompared to normal groupConclusion:TLR3were early and persistent overexpressed in the retina of diabeticrats.TLR3ligand poly(I:C) intravitreal injection aggravated retinal edemaand damage. Activation of TLR3may be aggravated DR by up-regulatingthe secretion of inflammatory cytokines IL-6, IL-1α, and TNF-α of retina.