Comparative Analysis of Urso- and Tauroursodeoxycholic Acid Neuroprotective Effects on Retinal Degeneration Models

• Authors: Alejandra Daruich, Sorbonne Universite; Emilie Picard, Sorbonne Universite; Justine Guegan, Sorbonne Universite; Thara Jaworski, Sorbonne Universite; Léa Parenti, Sorbonne Universite; Kimberley Delaunay, Sorbonne Universite; Marie-Christine Naud, Sorbonne Universite; Marianne Berdugo, Sorbonne Universite; Jeffrey Boatright, Emory University; Francine Behar-Cohen, Sorbonne Universite
• Journal Title: PHARMACEUTICALS
• Volume: Volume 15, Number 3
• Publisher: MDPI | 2022-03-01
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.3390/ph15030334
• Subjects: Health Sciences, Opthamology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Chemistry, Medicinal; Pharmacology & Pharmacy; UDCA; TUDCA; retina; retinal detachment; retinal degeneration; neuroprotection; PROTECTS; ACTIVATION; APOPTOSIS; SURVIVAL; RECEPTOR; TAURINE; MOUSE; CELLS

Abstract

Background: Ursodeoxycholic (UDCA) and tauroursodeoxycholic (TUDCA) acids have shown neuroprotective properties in neurodegenerative diseases, but differential effects of the two bile acids have been poorly explored. The aim of this study was to evaluate the neuroprotective effects of UDCA versus TUDCA in a neuroretinal degeneration model and to compare transcriptionally regulated pathways. Methods: The WERI-Rb-1 human cone-like cell line and retinal explants were exposed to albumin and TUDCA or UDCA. Viability, cell death, and microglial activation were quantified. Transcriptionally regulated pathways were analyzed after RNA sequencing using the edgeR bioconductor package. Results: Pre-treatment of cone-like cells with UDCA or TUDCA significantly protected cells from albumin toxicity. On retinal explants, either bile acid reduced apoptosis, necroptosis, and microglia activation at 6 h. TUDCA induced the regulation of 463 genes, whilst 31 genes were regulated by UDCA. Only nineteen common genes were regulated by both bile acids, mainly involved in iron control, cell death, oxidative stress, and cell metabolism. As compared to UDCA, TUDCA up-regulated genes involved in endoplasmic reticulum stress pathways and down-regulated genes involved in axonal and neuronal development. Conclusions: Either bile acid protected against albumin-induced cell loss. However, TUDCA regulated substantially more neuroprotective genes than UDCA.