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.
Highlights
Taurine is a free amino-sulfonic acid mainly provided by nutrition, which is present in large amounts in the central nervous system, and in the retina where it represents nearly half of the free amino-acid content [1]
Experiments on a Retinal ganglion cell (RGC) immortalized cell line supported the idea that taurine could directly affect RGC survival [20]. To further investigate this hypothesis, we have examined the effect of taurine on purified adult rat RGCs in culture, on RGCs subjected to the selective N-Methyl D-Aspartate (NMDA)-induced excitotoxicity in retinal explants and on RGCs undergoing degenerative processes in several animal models of retinal diseases
To assess the protective effect of taurine, RGCs were cultured in a serum deprivation condition that resulted in a low density of viable RGCs (3.360.3 RGC per field, n = 21; see Fig. 1G) when viability was revealed by calceinAM dye
Summary
Taurine is a free amino-sulfonic acid mainly provided by nutrition, which is present in large amounts in the central nervous system, and in the retina where it represents nearly half of the free amino-acid content [1]. Taurine appeared to play a major role in photoreceptor development [6,7]. Many studies investigated if taurine depletion could explain photoreceptor degeneration in different animal models of retinal diseases, a clear-cut link was never demonstrated [8]. A clinical study associating taurine, a calcium channel blocker (diltiazem) and vitamin E was reported to improve vision in patients with Retinitis pigmentosa [9]. Since these early discoveries involving taurine in photoreceptor development and survival, taurine was found to prevent neuronal excitotoxicty by reducing the glutamate-induced increase in intracellular calcium and endoplasmic reticulum stress [10,11]. No clear taurine neuroprotective effect has been demonstrated in cerebral ischemia [12]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
