Taurine provides neuroprotection against retinal ganglion cell degeneration

PLoS One. 2012;7(10):e42017. doi: 10.1371/journal.pone.0042017. Epub 2012 Oct 24.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Cells, Cultured
  • Mice
  • Mice, Inbred DBA
  • N-Methylaspartate / pharmacology
  • Neuroprotective Agents / pharmacology*
  • Photoreceptor Cells, Vertebrate / metabolism
  • Retinal Ganglion Cells / cytology
  • Retinal Ganglion Cells / drug effects*
  • Taurine / pharmacology*

Substances

  • Neuroprotective Agents
  • Taurine
  • N-Methylaspartate

Grants and funding

This work was supported by Institut National de la Sant? et de la Recherche M?dicale, Université Pierre et Marie Curie (Paris VI), the Fondation Ophtalmologique A. de Rothschild (Paris), Agence Nationale pour la Recherche (ANR: GLAUCOME), the European Community contrat TREATRUSH (n° HEALTH-F2-2010-242013), the Fédération des Aveugles de France, IRRP, the city of Paris, the Regional Council of Ile-de-France. L. Cadetti and NF received postdoctoral fellowships from the Fondation pour la Recherche Médicale, JM a doctoral fellowship from the Fundação para a Ciência e a Tecnologia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.