| First Author | Ren L | Year | 2017 |
| Journal | Toxicol Appl Pharmacol | Volume | 317 |
| Pages | 1-11 | PubMed ID | 28063877 |
| Mgi Jnum | J:239526 | Mgi Id | MGI:5829119 |
| Doi | 10.1016/j.taap.2017.01.001 | Citation | Ren L, et al. (2017) Myeloid differentiation protein 2-dependent mechanisms in retinal ischemia-reperfusion injury. Toxicol Appl Pharmacol 317:1-11 |
| abstractText | Retinal ischemia-reperfusion (I/R) injury is a common pathological process in many eye disorders. Oxidative stress and inflammation play a role in retinal I/R injury. Recent studies show that toll-like receptor 4 (TLR4) is involved in initiating sterile inflammatory response in retinal I/R. However, the molecular mechanism by which TLR4 is activated is not known. In this study, we show that retinal I/R injury involves a co-receptor of TLR4, myeloid differentiation 2 (MD2). Inhibition of MD2 prevented cell death and preserved retinal function following retinal I/R injury. We confirmed these findings using MD2 knockout mice. Furthermore, we utilized human retinal pigment epithelial cells (ARPE-19 cells) to show that oxidative stress-induced cell death as well as inflammatory response are mediated through MD2. Inhibition of MD2 through a chemical inhibitor or knockdown prevented oxidative stress-induced cell death and expression of inflammatory cytokines. Oxidative stress was found to activate TLR4 in a MD2-dependent manner via increasing the expression of high mobility group box 1. In summary, our study shows that oxidative stress in retinal I/R injury can activate TLR4 signaling via MD2, resulting in induction of inflammatory genes and retinal damage. MD2 may represent an attractive therapeutic target for retinal I/R injury. |
