Oral Ursodeoxycholic Acid Crosses the Blood Retinal Barrier in Patients with Retinal Detachment and Protects Against Retinal Degeneration in an Ex Vivo Model.

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License: CC BY 4.0
Serval ID
serval:BIB_5C087AEA6F19
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Oral Ursodeoxycholic Acid Crosses the Blood Retinal Barrier in Patients with Retinal Detachment and Protects Against Retinal Degeneration in an Ex Vivo Model.
Journal
Neurotherapeutics
Author(s)
Daruich A., Jaworski T., Henry H., Zola M., Youale J., Parenti L., Naud M.C., Delaunay K., Bertrand M., Berdugo M., Kowalczuk L., Boatright J., Picard E., Behar-Cohen F.
ISSN
1878-7479 (Electronic)
ISSN-L
1878-7479
Publication state
Published
Issued date
04/2021
Peer-reviewed
Oui
Volume
18
Number
2
Pages
1325-1338
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Rhegmatogenous retinal detachment (RD) is a threatening visual condition and a human disease model for retinal degenerations. Despite successful reattachment surgery, vision does not fully recover, due to subretinal fluid accumulation and subsequent photoreceptor cell death, through mechanisms that recapitulate those of retinal degenerative diseases. Hydrophilic bile acids are neuroprotective in animal models, but whether they can be used orally for retinal diseases is unknown. Ursodeoxycholic acid (UDCA) being approved for clinical use (e.g., in cholestasis), we have evaluated the ocular bioavailability of oral UDCA, administered to patients before RD surgery. The level of UDCA in ocular media correlated with the extent of blood retinal barrier disruption, evaluated by the extent of detachment and the albumin concentration in subretinal fluid. UDCA, at levels measured in ocular media, protected photoreceptors from apoptosis and necrosis in rat retinal explants, an ex vivo model of RD. The subretinal fluid from UDCA-treated patients, collected during surgery, significantly protected rat retinal explants from cell death, when compared to subretinal fluid from control patients. Pan-transcriptomic analysis of the retina showed that UDCA upregulated anti-apoptotic, anti-oxidant, and anti-inflammatory genes. Oral UDCA is a potential neuroprotective adjuvant therapy in RD and other retinal degenerative diseases and should be further evaluated in a clinical trial.
Keywords
Retinal degeneration, TUDCA, UDCA, neuroprotection, retinal detachment, ursodeoxycholic acid
Pubmed
Web of science
Open Access
Yes
Create date
23/02/2021 8:35
Last modification date
12/01/2022 7:10
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