Taurine Promotes Retinal Ganglion Cell Survival Through GABAB Receptor Activation

Abstract

Retinal ganglion cell (RGC) degeneration occurs in numerous retinal diseases, either as a primary process like in glaucoma, or secondary to photoreceptor loss and no efficient compound targeting directly RGC neuroprotection is yet available. We previously described that taurine exerts a direct protective effect on RGCs cultured under serum-deprived conditions. Because taurine was known to have an agonist-like activity for GABA/glycine receptors, we investigated here if the taurine-elicited neuroprotective effect may be mediated through the activation of these receptors using selective antagonist ligands. RGCs were purified, seeded in 96-well plate and maintained in culture during 6 days in vitro. Viable cells were labelled with calcein and densities in full-well area were then automatically counted. Here we show that the protective effect of taurine against RGC loss observed under serum deprivation can be mediated through the GABA receptor stimulation. Hence, two selective agonists, including baclofen, at this metabotropic GABA receptor were found to reproduce taurine action by enhancing RGC survival in culture. This study suggests that GABA receptor stimulation provides direct neuroprotection for RGCs. Accordingly, drugs targeting GABA receptor may represent a new way for the prevention of RGC degeneration.

Synapse and Receptor Alterations in Two Different S100B-Induced Glaucoma-Like Models

“…In a glaucoma animal model induced by chronic IOP, intraocular injection of the brain-derived neurotrophic factor increased the number of ribbon synapses [ 89 ]. Likewise, therapeutic approaches altering retinal NMDA [ 90 , 91 ] and GABA receptors [ 65 , 92 ] as well as the interaction between them and their synaptic proteins [ 93 ] seem to be promising.…”

<p>Systemic taurine treatment provides neuroprotection against retinal photoreceptor degeneration and visual function impairments</p>

“…Moreover, taurine acts as a neurotransmitter via specific receptors and interferes with functions of other transmitter systems 33,34. For instance, taurine can activate the GABA B receptor and promote RGCs survival, thereby modifying the progress rate of retinal degeneration 35. Taurine and glutamate are reciprocally inhibiting each other, thereby contributing to fine-tuning visual signals in the retinal circuits 36.…”

Natural Products: Evidence for Neuroprotection to Be Exploited in Glaucoma

“…Although the mechanism underlying the protective effect of taurine on RGCs is not completely clarified, it was suggested that it inhibits NADPH oxidases, which are the primary source of superoxide induced by NMDA receptor activation [ 204 ]. Successively, it was demonstrated that the selective blockade of taurine transporter prevented the taurine-mediated increase of RGC survival, suggesting that the neuroprotective effects of taurine are mediated by its intracellular/mitochondrial action [ 205 ].…”

“…Taurine is structurally related to the neurotransmitter gamma aminobutyric acid (GABA); therefore, it has been suggested that its neuroprotective effects could be mediated by the interaction with GABA receptors [ 190 ]. Indeed, GABA-B receptors antagonist prevented the taurine-elicited neuroprotective effect in RGCs [ 205 ].…”