Taurine protecting ganglion cells against glutamate-induced excitotoxicity by stabilizing calcium homeostasis

摘要

Taurine is known to act as an osmoregulator and an inhibitory neuromodulator in central nervous system．Recent researches suggest that taurine Selves as a neuroprotector,which may explain its protective effect against glutamate-induced excitotoxicity．Glutamate-induced excito-toxicity has been implicated as an important cause of death of retinal ganglion cells (RGCs) in retinal ischemia,glaucoma,and degenerative retinopathy．The purpose of this study was to determine whether taurine has neuroprotective effects against glutamate-induced excitotoxicity in RGCs in vitro models．We used two different primary cultures,one is a rat retinal neuron culture，in which neurotoxicity was induced by using 1 mmol／L glutamate and cell viability was assessed by trypan blue exclusion method，the other is a purified RGCs culture．which used 25 μ mol／L glutamate for three days to trigger neurotoxicity and cell viability WaS assessed by calcein-AM staining living RGCs．TUNEL test and immunofluorescence staining of Thy-1 are used to observe the protective effects of taurine on cultured RGCs，plus confocal microscope Ca2+ imaging analysis of changed[Ca2+]i of RGCs to explore the protective mechanisms．It was founded that taurine (0.1-10mmol/L) reduced the glutamate-induced neuronal death in both retinal neuron and RGCs cultures by a concentration-dependent manner. The effect of taurine was significant at 1 and 10 mmol/L. Taurine also reduced glutamate-induced RGCs apoptosis and Thy-1 expression significantly. In purified cultured RGCs, glutamate-induced elevation of [Ca2+]i is reduced to the basal level upon addition of 1 mol/L taurine, and pretreament of RGCs with taurine greatly suppresses the elevation of [Ca2+]i induced by glutamate. We conclude from these data that taurineexerts a direct neuroprotective effect against glutamate-induced neuronal cell death in retinal neuron and RGCs primary cultures. Our study also implies that taudne protects RGCs against glutamate-inducedexcitotoxicity primarily through modulation of intracellular calcium.