Neuroprotective effects of lutein on inner retinal neurons in a model of acute retinal ischemia/reperfusion

Abstract

Retinal ischemia/reperfusion (I/R) is common in many ocular diseases, and leads to irreversible neuronal cell and structural damage. It is well known that lutein, one of the potent antioxidants, protects retina in age-related macular degeneration (AMD). However, the neuroprotective effect of lutein on retinal I/R is not yet explored. In the present study, acute unilateral retinal I/R was induced by the blockade of internal carotid artery using intraluminal method in mice. Here, 2 hrs of ischemia was induced followed by 22 hrs of reperfusion. At 1 hr before and 1 hr after the onset of reperfusion either lutein or vehicle was administrated by intraperitoneal injection. Our findings showed that severe neuronal cell loss in retinal ganglion cells (RGCs) and inner retinal swelling was observed in retina after I/R insult. Ischemia also caused deleterious effect on other inner retinal neurons, including amacrine cells, bipolar cells and horizontal cells. In addition, expression levels of two oxidative stress markers, nitrotyrosine and poly(ADP-ribose), were elevated in ischemic retina. However, lutein administration protected RGCs as well as other inner retinal cells. Besides, retinal swelling induced by I/R was reduced after lutein treatment. Oxidative stress was obviously decreased in lutein-treated retina. Result herein demonstrated that lutein rescued the retina from I/R insult. Moreover, lutein improved the neurological behavior and decreased the death rate, indicating that lutein may exert important neuroprotective effects on tissues other than on retina alone. This study provides more information on the neuroprotection of retinal neurons by lutein after acute retinal I/R injury. Most importantly, our study is the first to show that lutein is beneficial to inner retinal neurons. In addition, the current study provides more insights on broadening the use of lutein to prevent or retard the progression of retinal pathologies other than AMD in the future.