Taurine Provides Neuroprotection against Retinal Ganglion Cell Degeneration

被引:72
作者
Froger, Nicolas [1 ,2 ,3 ]
Cadetti, Lucia [1 ,2 ,3 ]
Lorach, Henri [1 ,2 ,3 ]
Martins, Joao [1 ,2 ,3 ]
Bemelmans, Alexis-Pierre [1 ,2 ,3 ]
Dubus, Elisabeth [1 ,2 ,3 ]
Degardin, Julie [1 ,2 ,3 ]
Pain, Dorothee [1 ,2 ,3 ]
Forster, Valerie [1 ,2 ,3 ]
Chicaud, Laurent [1 ,2 ,3 ]
Ivkovic, Ivana [1 ,2 ,3 ]
Simonutti, Manuel [1 ,2 ,3 ]
Fouquet, Stephane [1 ,2 ,3 ]
Jammoul, Firas [1 ,2 ,3 ]
Leveillard, Thierry [1 ,2 ,3 ,4 ]
Benosman, Ryad [1 ,2 ,3 ,5 ,6 ]
Sahel, Jose-Alain [1 ,2 ,3 ,4 ,7 ,8 ,9 ]
Picaud, Serge [1 ,2 ,3 ,8 ]
机构
[1] Inst Vis, INSERM, UMR 968, Paris, France
[2] Univ Paris 06, UMR S 968, Inst Vis, Paris, France
[3] CNRS, UMR7210, Inst Vis, Paris, France
[4] Ctr Hosp Natl Ophtalmol Quinze Vingts, Paris, France
[5] Univ Paris 06, Inst Syst Intelligents & Robot, Paris, France
[6] CNRS, UMR7222, Paris, France
[7] UCL, Inst Ophthalmol, London, England
[8] Fdn Ophtalmol Adolphe Rothschild, Paris, France
[9] French Acad Sci, Paris, France
关键词
ANGLE-CLOSURE GLAUCOMA; AMINO-ACIDS; RAT RETINA; VIGABATRIN TOXICITY; PHOTORECEPTOR LOSS; DIABETES-MELLITUS; OPTIC ATROPHY; SECONDARY; DEFICIENCY; TRANSPORT;
D O I
10.1371/journal.pone.0042017
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
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.
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页数:11
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