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Published on: February 19, 2012
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Comparative Analysis of Urso- and Tauroursodeoxycholic Acid Neuroprotective Effects on Retinal Degeneration Models
Alejandra Daruich1,2, Emilie Picard1, Justine Guégan3
1From Physiopathology of Ocular Diseases to Clinical Development, Centre de Recherche des Cordeliers, Sorbonne University, Paris University, Inserm, F-75006 Paris, France.
Pharmaceuticals (Basel, Switzerland)
|March 26, 2022
Summary
Ursodeoxycholic (UDCA) and tauroursodeoxycholic (TUDCA) acids show neuroprotective effects. TUDCA regulated more genes than UDCA, suggesting broader therapeutic potential in neurodegenerative diseases.
Area of Science:
- Ophthalmology
- Neuroscience
- Biochemistry
Background:
- Bile acids, ursodeoxycholic acid (UDCA) and tauroursodeoxycholic acid (TUDCA), exhibit neuroprotective properties.
- Differential effects and transcriptional impacts of UDCA and TUDCA remain underexplored in neurodegenerative contexts.
Purpose of the Study:
- To compare the neuroprotective effects of UDCA and TUDCA in a neuroretinal degeneration model.
- To analyze and contrast the transcriptionally regulated pathways influenced by UDCA and TUDCA.
Main Methods:
- Utilized WERI-Rb-1 human cone-like cells and retinal explants exposed to albumin.
- Assessed cell viability, cell death, and microglial activation.
- Performed RNA sequencing and differential gene expression analysis using edgeR.
Main Results:
- Both UDCA and TUDCA protected cone-like cells and retinal explants from albumin-induced toxicity, reducing apoptosis, necroptosis, and microglial activation.
- TUDCA regulated significantly more genes (463) than UDCA (31), with only 19 common genes affected.
- TUDCA modulated endoplasmic reticulum stress pathways and downregulated axonal/neuronal development genes, while UDCA's effects were less extensive.
Conclusions:
- Both UDCA and TUDCA offer protection against neuroretinal degeneration.
- TUDCA demonstrates a broader transcriptional impact, regulating a greater number of genes, including those involved in neuroprotection, compared to UDCA.
