Anti-inflammatory effects of lutein in retinal ischemic/hypoxic injury : in vivo and in vitro studies

Abstract

PURPOSE. Lutein protects retinal neurons by its anti-oxidative and anti-apoptotic properties in ischemia/reperfusion (I/R) injury while its anti-inflammatory effects remain unknown. As Muller cells play a critical role in retinal inflammation, the effect of lutein on Muller cells was investigated in a murine model of I/R injury and a culture model of hypoxic damage. METHODS. Unilateral retinal I/R was induced by a blockade of internal carotid artery using the intraluminal method in mice. Ischemia was maintained for 2 hours followed by 22 hours of reperfusion, during which either lutein (0.2 mg/kg) or vehicle was administered. Flash electroretinogram (flash ERG) and glial fibrillary acidic protein (GFAP) activation were assessed. Lutein's effect on Muller cells was further evaluated in immortalized rat Muller cells (rMC-1) challenged with cobalt chloride-induced hypoxia. Levels of IL-1 beta, cyclooxygenase-2 (Cox-2), TNF alpha, and nuclear factor-NF-kappa-B (NF-kappa B) were examined by Western blot analysis. RESULTS. Lutein treatment minimized deterioration of b-wave/a-wave ratio and oscillatory potentials as well as inhibited up-regulation of GFAP in retinal I/R injury. In cultured Muller cells, lutein treatment increased cell viability and reduced level of nuclear NF-kappa B, IL-1 beta, and Cox-2, but not TNF alpha after hypoxic injury. CONCLUSIONS. Reduced gliosis in I/R retina was observed with lutein treatment, which may contribute to preserved retinal function. Less production of pro-inflammatory factors from Muller cells suggested an anti-inflammatory role of lutein in retinal ischemic/hypoxic injury. Together with our previous studies, our results suggest that lutein protected the retina from ischemic/hypoxic damage by its anti-oxidative, antiapoptotic, and anti-inflammatory properties.