Interleukin-33 Prevents Retinal Ischemia Reperfusion Injury in Rats by Preventing Apoptosis

Abstract

Background: Retinal ischemia reperfusion (RIR) injury is a common pathological process that can result in visual impairment in many ophthalmic diseases. Inflammation and apoptosis play an important role in RIR injury. Objectives: This experimental study was designed to explore the ability of a new cytokine, IL-33, to attenuate RIR injury via an apoptosis-inhibitory mechanism. Methods: From June, 2015 to October, 2015, 40 Sprague-Dawley (SD) rats from Wuhan university in China were divided into the following four groups: normal control group (NCG), RIR injury model group (MG), IL-33 pretreatment group (IL-33), and PBS group (PBS) according to random number tables. Rats in the IL-33 and PBS groups received an intravitreous injection of 2 μg of recombinant IL-33 (rIL-33) or PBS one hour before the induction of ischemia. Histological evaluation, inflammatory cell infiltration, and apoptosis of retinal cells were examined. The expressions of apoptotic-related proteins (Bcl-2 and Bax) were quantified by immunohistochemistry and western blotting. The presence of NF-κB p65 in the retina was assessed by western blotting. Results: Our data revealed that IL-33 pretreatment maintained a better retinal structure, inhibited leukocyte infiltration (IL-33 vs. MG with P < 0.01 and IL-33 vs. PBS group with P < 0.01), and reduced the apoptosis of retinal ganglion cells (IL-33 vs. MG with P < 0.05 and IL-33 vs. PBS group with P < 0.05). Furthermore, IL-33 upregulated the expression of Bcl-2and decreased the expression of Bax (IL-33 vs. MG with P < 0.01 and IL-33 vs. PBS group with P < 0.01). In addition, IL-33 attenuated NF-κB p65 levels in the retina and inhibited the activation of NF-κB (IL-33 vs. MG with P = 0.021 and IL-33 vs. PBS group with P = 0.025). Conclusions: IL-33 may be a potential new agent to attenuate RIR injury by reducing inflammatory cell infiltration and preventing apoptosis.