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Nicolas G. Froger, Dorothée Pain, Valérie Forster, Ivana Ivkovic, José-Alain Sahel, Serge Picaud; Taurine Enhances Retinal Ganglion Cell Survival Through GabaB Receptor Activation. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4652.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal ganglion cells (RGC) degeneration occurs in numerous retinal diseases, either as a primary process like in glaucoma, or secondary to photoreceptor loss. No commercial drug targeting directly RGC neuroprotection is yet available. Recently, we showed that taurine, a sulfonic acid, can directly enhance RGC survival in different models of RGC degeneration. Because taurine was known to have a GABA/glycine receptor agonist-like activity, we investigated here if the taurine neuroprotective effect was mediated through GABA receptor activation using selective ligands.
RGC were purified from adult rat retinae using immunopanning technique, and seeded in a 96-well plate for 6 days in vitro (DIV) in a neurobasal medium with serum deprivation. GABA/glycine receptor antagonists (Strychnine 10µM, Picrotoxin 100µM and CGP35348 30µM) were incubated with taurine (1mM) directly into the culture medium during the whole period of culture. Moreover, GABAB receptor agonists, baclofen (100µM) and SFK97541 (100µM), were also tested. RGC survival was then evaluated by counting calcein-positive RGCs.
As previously observed, taurine was found to significantly increase the RCG survival in (+52%) compared to control untreated cells. Addition with taurine of both GABAA (picrotoxin 100µM) and glycine receptor blockers (strychnine 10µM) did not modify the neuroprotective effect of taurine. By contrast, co-incubation of a GABAB receptor antagonist (CGP35348 30µM) with taurine significantly reduces the taurine-elicited RGC survival. Interestingly, adding GABAB receptor agonists, baclofen or SKF97541, in the culture medium, reproduced the protective effect of taurine by stimulating the RGC survival (+31% and +24%, respectively).
These data show that the protective effect of taurine on RGC degeneration is mediated through the GABAB receptor stimulation. Furthermore, the selective agonists at this metabotropic GABA receptor were found to reproduce taurine action by enhancing RGC survival in culture. This study firstly demonstrates that GABAB receptor stimulation provides neuroprotection. Future experiments will investigate intracellular mechanisms responsible for this new pathway for neuroprotection.
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