Lycium barbarum extracts preserve retinal function and reduce neuronal damage in a mouse model of transient retinal ischemia

Abstract

PURPOSE: Retinal ischemia is a common feature shared by many blindness-causing eye diseases including retinal vascular occlusion, diabetic retinopathy, glaucoma, and retinopathy of prematurity. Retinal dysfunction and neuronal cell death are complications of ischemic insult. We aim to investigate the neuroprotective effects of Lycium barbarum polysaccharides (LBP), extracts from an anti-aging and anti-oxidation Oriental medicine, on visual function and retinal neurons in a mouse model of transient retinal ischemia. METHODS: Retinal ischemia was induced by intraluminal filamentous occlusion of the internal carotid artery for 2 hours and reperfusion was allowed by filament removal. Either LBP or phosphate-buffered saline was administered daily through a gastric tube for 7 days prior to retinal ischemia as well as 1 day, 3 days and 7 days after reperfusion. Scotopic electroretinography was performed to evaluate visual function. Paraffin-embedded retinal sections were prepared 7 days after reperfusion. Viable cells in the ganglion cell layer were counted and inner retinal thickness was measured. Expression levels of protein kinase C (PKC-α), calretinin, glial fibrillary acidic protein (GFAP) and glutamine synthase were investigated by immunohistochemistry. RESULTS: 2-hour retinal ischemia leads to sustained inhibition of b- wave amplitude and oscillatory potentials (OPs). LBP-treated mice exhibited greater b-wave and OPs responses at 1 day, 3 days and 7 days after reperfusion indicating persistent functional protection of bipolar cells, amacrine cells and Müller cells. In addition, ischemic insult resulted in fewer viable cells and decreased retinal thickness, as well as reduced immunoreactivity of PKC-α, fewer calretinin-positive cells and increased expression of GFAP. These changes were diminished in LBP-treated retina which was in line with the electroretinography findings. CONCLUSIONS: LBP treatment effectively preserved retinal function as well as reduced neuronal death and glial activation. The present study suggests that LBP may serve as a neuroprotective agent in retinal ischemic diseases.