Effect of lidocaine on retinal aquaporin-4 expression after ischemia/reperfusion injury in the rat

BACKGROUND: Several studies have demonstrated that high doses of lidocaine can reduce edema in rats with brain injury by down-regulating aquaporin-4 (AQP4) expression. The hypothesis for the present study is that lidocaine could retinal edema that is associated with AQP4 expression. OBJECTIVE: This study was designed to investigate the interventional effects of lidocaine on retinal AQP4 expression and retinal edema following ischemia/reperfusion injury in the rat. DESIGN, TIME AND SETTING: This study, a randomized, controlled, animal experiment, was performed at the Basic Research Institute, Chongqing Medical University from September 2006 to May 2007. MATERIALS: Seventy-five, healthy, adult, female, Sprague-Dawley rats were included. A total of 50 rats were used to establish a retinal ischemia/reperfusion injury model using an anterior chamber enhancing perfusion unit. Rabbit anti-rat AQP4 antibody was purchased from Santa Cruz Biotechnology, USA. METHODS: All 75 rats were randomly divided into three groups, with 25 rats in each: control, model, and lidocaine. At each time point (1, 6, 12, 24, and 48 hours after modeling, five rats for each time point), each rat in the lidocaine group was intraperitoneally administered lidocaine with an initial dose of 30 mg/kg, followed by subsequent doses of 15 mg/kg every six hours. The entire treatment process lasted three days for each rat. At each above-mentioned time point, rats in the model group were modeled, but not administered any substances. Rats in the control group received the same treatments as in the lidocaine group except that lidocaine was replaceld by physiological saline. MAIN OUTCOME MEASURES: Following hematoxylin-eosin staining, rat retinal tissue was observed to investigate retinal edema degree through the use of an optical microscope and transmission electron microscope. Retinal AQP4 expression was determined by immunohistochemistry. RESULTS: At each above-mentioned time point, AQP4 expression was significantly increased in the model group compared to the control group (P < 0.05); this change was consistent with the degree of retinal edema. In the lidocaine group, retinal AQP4 expression was significantly decreased (P < 0.05), and retinal edema was reduced, compared with the model group. CONCLUSION: Lidocaine inhibits rat retinal AQP4 expression following ischemia/reperfusion injury, leading to a reduction of retinal edema.