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 Müller cells play a critical role in retinal inflammation, the effect of lutein on Müller 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 Müller cells was further evaluated in immortalized rat Müller cells (rMC-1) challenged with cobalt chloride-induced hypoxia. Levels of IL-1b, cyclooxygenase-2 (Cox-2), TNFa, and nuclear factor-NF-kappa-B (NF-jB) were examined by Western blot analysis. RESULTS.Lutein treatment minimized deterioration of b-wave/awave ratio and oscillatory potentials as well as inhibited upregulation of GFAP in retinal I/R injury. In cultured Müller cells, lutein treatment increased cell viability and reduced level of nuclear NF-jB, IL-1b, and Cox-2, but not TNFa 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 Müller 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. (Invest Ophthalmol Vis Sci. 2012;53:5976-5984)

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

“…Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and other inflammatory mediators, through a series of cascade reactions, may induce leukocyte infiltration to the lesions, block the capillaries, and damage the microvascular endothelium, leading to low perfusion. The infiltrating leukocytes further produce large amounts of cytokines, chemokines, and matrix met- alloproteinases (MMPs), causing blood-retinal barrier destruction and aggravating the injury, ultimately resulting in retinal neuronal cell death (23,24). However, there are also some protective cytokines in RIR injury.…”

Lipid and Protein Oxidation in Newborn Infants after Lutein Administration

“…Together these results strongly support the hypothesis that lutein given orally may have protective effects on organs and tissues. Lutein seems to have not only antioxidant activity but also anti-inflammatory action as it has been recently reported [36]. Lutein inhibits arachidonic acid release from a macrophage cell line, blocking cytosolic phospholipase A2 activity [37].…”

Dynamic, in vivo, real-time detection of retinal oxidative status in a model of elevated intraocular pressure using a novel, reversibly responsive, profluorescent nitroxide probe

“…Various carotenoids are present in human plasma, but only the xanthophylls lutein and zeaxanthin are found in retina in considerable amounts (Junghans et al, 2001). Lutein, a potent antioxidant, has been applied in human clinical trials and shown to improve vision and retard the progression of AMD and cataract development (Chasan-Taber et al, 1999;Itagaki et al, 2006;Li et al, 2009;Li and Lo, 2010;Richer et al, 2007;Richer et al, 2004), however the mechanism of protection is unclear and the role of lutein in ischemic injury is limited (Li et al, 2012). In vitro studies show lutein can penetrate into cells and scavenge intracellular H 2 O 2 preventing cell damage (Li and Lo, 2010) suggesting a possible therapeutic benefit to antioxidant intervention for diseases linked to oxidative stress.…”