Lutein preserved retinal function and minimized inflammatory response in retinal ischemia/reperfusion injury

Abstract

PURPOSE. Retinal ischemia/reperfusion (I/R) injury is a feature of ocular pathologies such as amaurosis fugax and acute angle-closure glaucoma, leading to irreversible neuronal damage and visual impairment. Our previous studies showed that lutein is neuroprotective in retinal I/R injury. Besides being anti-apoptotic and anti-oxidative, lutein is also implicated to be anti-inflammatory. As Müller cell plays a critical role in inflammation in retinal diseases, the effect of lutein on Müller cells was investigated in a mouse retinal I/R injury model and a chemical-induced hypoxia cell culture model. METHODS. Male C57Bl/6N mice were challenged with 2-hour retinal ischemia followed by 22-hour reperfusion by intraluminal blockade of the internal carotid artery that provides blood supply to the eye. Lutein (0.2mg/kg) or vehicle (10% DMSO) was administered by intraperitoneal injection at 1 hour before and 1 hour after reperfusion. Electroretinography (ERG) and GFAP immunoreactivity were examined in retinal sections. On the other hand, in vitro hypoxia was induced in a retinal Müller cell line (rMC-1) with cobalt (II) chloride. Western blotting of IL-1β, Cox-2, TNFα, and NFκB were then performed to assess the effect of lutein administration. RESULTS. With lutein post-treatment, the deterioration in ERG response and the activation of retinal GFAP were minimized in the animal model of retinal I/R injury. In the cell culture model of hypoxia, lutein administration decreased the levels of IL-1β, Cox-2 and nuclear NFκB but not TNFα. CONCLUSIONS. Lutein post-treatment preserved retinal function and reduced Müller cell gliosis after retinal I/R injury. The reduction of inflammatory factor production from Müller cells after lutein administration suggested an anti-inflammatory role of lutein. Together with our previous studies, these results indicate that lutein protects the retina from I/R damage by its anti-oxidative, anti-apoptotic and anti-inflammatory properties, making lutein an attractive therapeutic agent in eye diseases in which acute ischemia is a feature.