• Galina Dvoriantchikova, Andrea Rachelle C Santos, Dagmara Danek, Xenia Dvoriantchikova, and Dmitry Ivanov.
• Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 1638 NW 10th Ave, Miami, FL, 33136, USA.
• Eur. J. Neurosci. 2014 Aug 1; 40 (3): 2502-12.

AbstractToll-like receptor 4 (Tlr4) plays an important role in ischemia-reperfusion (IR)-induced retinal inflammation and damage. However, the role of two Tlr4-dependent signaling cascades, myeloid differentiation primary response 88 (Myd88) and TIR-domain-containing adapter inducing interferon-β (Trif), in retinal IR injury is poorly understood. In this study, we investigated the contribution of the Myd88-dependent and Trif-dependent signaling cascades in retinal damage and inflammation triggered by IR, by using Myd88 knockout (Myd88KO) and Trif knockout (TrifKO) mice. Retinal IR injury was induced by unilateral elevation of intraocular pressure for 45 min by direct corneal cannulation. To study IR-induced retinal ganglion cell (RGC) death in vitro, we used an oxygen and glucose deprivation (OGD) model. Our data suggested that Myd88 was present in many retinal layers of sham-operated and ischemic mice, whereas Trif was mainly present in the ganglion cell layer (GCL). The level of Myd88 was increased in the retina after IR. We found that retinas of TrifKO mice had a significantly reduced neurotoxic pro-inflammatory response and significantly increased survival of the GCL neurons after IR. Although Myd88KO mice had relatively low levels of inflammation in ischemic retinas, their levels of IR-induced retinal damage were notably higher than those of TrifKO mice. We also found that Trif-deficient RGCs were more resistant to death induced by OGD than were RGCs isolated from Myd88KO mice. These data suggested that, as compared with the Myd88-dependent signaling cascade, Trif signaling contributes significantly to retinal damage after IR.© 2014 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

27 keywords...

hide…