Purchase this article with an account.
Nicolas Cuenca, Violeta Gomez-Vicente, Francisco Germain, Laura Fernandez-Sanchez, Miguel Angel Company, Pedro de la Villa, Mercedes Palmero; Efficacy Of TUDCA In Preventing Retinal Ganglion Cell Death In The RGC-5 Cell Line And Following Intravitreal Injection Of NMDA. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3473.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Several studies have previously shown the anti-apoptotic properties of the bile constituent, tauroursodeoxycholic acid (TUDCA), in diverse models of photoreceptor degeneration. The aim of this study is to extend these findings to other retinal neuronal types and to test whether systemic administration of TUDCA protects retinal ganglion cells from death following oxidative or excitotoxic insults.
Apoptosis was induced in the RGC-5 cell line (kindly provided by Dr. N. Agarwal) after exposure to the nitric oxide donor sodium nitroprusside, in the presence of increasing concentrations of TUDCA. Viability was assessed by XTT and crystal violet assays, and loss of mitochondrial potential with the JC-1 probe. In vivo experiments were carried out in Sprague-Dawley rats and C57BL/6mice. Retinal ganglion cell death was induced by intravitreal injection of N-methyl-d-aspartate (NMDA) in TUDCA (500 mg/kg i.p.) or vehicle-treated animals. Immunohistochemistry on whole-mount retinas was used to evaluate retinal ganglion cell survival.
When cultured in the presence of TUDCA, survival of sodium nitroprusside-treated RGC-5 cells significantly increased in a dose-dependent manner. Viability values reached up to 80-90% of control untreated cells, which correlated with the preservation of mitochondrial potential. In vivo, TUDCA delayed NMDA-induced apoptosis of retinal ganglion cells, as revealed by Brn3a immunostaining of whole-mounts. However, for high concentrations of NMDA the effect of TUDCA is less significant.
Our results sustain the efficacy of TUDCA in preventing retinal ganglion cell death, thus, TUDCA would be a good candidate for the pharmacological treatment of degenerative diseases coursing with retinal ganglion cell loss.
This PDF is available to Subscribers Only