Taurine Provides Neuroprotection against Retinal Ganglion Cell Degeneration

Abstract

Retinal ganglion cell (RGC) degeneration occurs in numerous retinal diseases leading to blindness, either as a primary process like in glaucoma, or secondary to photoreceptor loss. However, no commercial drug is yet directly targeting RGCs for their neuroprotection. In the 70s, taurine, a small sulfonic acid provided by nutrition, was found to be essential for the survival of photoreceptors, but this dependence was not related to any retinal disease. More recently, taurine deprivation was incriminated in the retinal toxicity of an antiepileptic drug. We demonstrate here that taurine can improve RGC survival in culture or in different animal models of RGC degeneration. Taurine effect on RGC survival was assessed in vitro on primary pure RCG cultures under serum-deprivation conditions, and on NMDA-treated retinal explants from adult rats. In vivo, taurine was administered through the drinking water in two glaucomatous animal models (DBA/2J mice and rats with vein occlusion) and in a model of Retinitis pigmentosa with secondary RGC degeneration (P23H rats). After a 6-day incubation, 1 mM taurine significantly enhanced RGCs survival (+68%), whereas control RGCs were cultured in a taurine-free medium, containing all natural amino-acids. This effect was found to rely on taurine-uptake by RGCs. Furthermore taurine (1 mM) partly prevented NMDA-induced RGC excitotoxicity. Finally, taurine supplementation increased RGC densities both in DBA/2J mice, in rats with vein occlusion and in P23H rats by contrast to controls drinking taurine-free water. This study indicates that enriched taurine nutrition can directly promote RGC survival through RGC intracellular pathways. It provides evidence that taurine can positively interfere with retinal degenerative diseases.

Taurine Depletion Causes ipRGC Loss and Increases Light-Induced Photoreceptor Degeneration

“…This suggests that taurine supplementation may be beneficial to prevent retinal degenerations that proceed with photoreceptor or RGC loss and in which light may also be a critical etiologic factor, such as inherited retinal degeneration, AMD, or glaucoma. 10,22,95,96 Finally, our data also suggest that taurine supplementation may be beneficial to prevent retinal degenerations in which S-cone degeneration is the initial event, such as the photoreceptor degenerations that are initiated or worsened by light.…”

Quantitative and Topographical Analysis of the Losses of Cone Photoreceptors and Retinal Ganglion Cells Under Taurine Depletion

“…[47][48][49] A direct insult to RGCs under conditions of taurine depletion is also supported by a histopathological study of the retina from a vigabatrin-treated patient suggesting that RGCs were the primary site of the lesion. 11 Indeed, we have shown that pure RGCs survive better in culture with the addition of taurine in the medium, 49 consistent with the notion that in vivo taurine depletion can directly induce RGC degeneration. This RGC loss is consistent with the RGC degeneration observed in vigabatrin-treated animals also exhibiting taurine depletion.…”

New strategies for neuroprotection in glaucoma, a disease that affects the central nervous system

“…Interestingly, in 2012, Froger and colleagues reported a protective effect of the amino acid taurine against excitotoxicity showing increase RGC survival in vivo and in vitro and suggesting that enriched taurine nutrition can directly promote RGC survival (Froger et al, 2012). Moreover, nafamostat mesilate, a serine protease inhibitor showed protection against NMDA-induced neuronal and vascular damage in rat retinas (Tsuda et al, 2012).…”