Neuroprotective Effect of Tauroursodeoxycholic Acid on N-Methyl-D-Aspartate-Induced Retinal Ganglion Cell Degeneration

Abstract

Retinal ganglion cell degeneration underlies the pathophysiology of diseases affecting the retina and optic nerve. Several studies have previously evidenced the anti-apoptotic properties of the bile constituent, tauroursodeoxycholic acid, in diverse models of photoreceptor degeneration. The aim of this study was to investigate the effects of systemic administration of tauroursodeoxycholic acid on N-methyl-D-aspartate (NMDA)-induced damage in the rat retina using a functional and morphological approach. Tauroursodeoxycholic acid was administered intraperitoneally before and after intravitreal injection of NMDA. Three days after insult, full-field electroretinograms showed reductions in the amplitudes of the positive and negative-scotopic threshold responses, scotopic a- and b-waves and oscillatory potentials. Quantitative morphological evaluation of whole-mount retinas demonstrated a reduction in the density of retinal ganglion cells. Systemic administration of tauroursodeoxycholic acid attenuated the functional impairment induced by NMDA, which correlated with a higher retinal ganglion cell density. Our findings sustain the efficacy of tauroursodeoxycholic acid administration in vivo, suggesting it would be a good candidate for the pharmacological treatment of degenerative diseases coursing with retinal ganglion cell loss.

Phosphorylated α‐synuclein in the retina is a biomarker of Parkinson's disease pathology severity

“…In whole‐mount retinas, the incubation times were longer: 3 days for the primary antibodies, which included, for some sections, double staining with rabbit polyclonal anti‐RBPMS (RNA‐binding protein with multiple splicing), diluted 1:1,000, and 2 days for the secondary antibody (Alexa Fluor 555 donkey antirabbit IgG at a 1:100 dilution). The RBPMS antibody was a generous gift from Dr. Nicholas Brecha and specifically recognizes retinal ganglion cells . Retinas were flat‐mounted in Citifluor (Citifluor Ltd, London, UK) with the ganglion cell layer side up.…”

“…The RBPMS antibody was a generous gift from Dr. Nicholas Brecha and specifically recognizes retinal ganglion cells. 31 Retinas were flat-mounted in Citifluor (Citifluor Ltd, London, UK) with the ganglion cell layer side up. Fluorescence images were taken using a TCS SP2 confocal laser-scanning microscope (Leica Microsystems).…”

Bile Acids in Neurodegenerative Disorders

“…This model of excitotoxicity causes disruption of sodium-potassium balance, calcium overload, mitochondrial dysfunction, and oxidative stress (Gomez-Vicente et al, 2015). In mice, administration of TUDCA prior to the intravitreal injection of NMDA was found to increase survival of retinal ganglion cells.…”

Pathologic confirmation of retinal ganglion cell loss in multiple system atrophy

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