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Oral Ursodeoxycholic Acid Crosses the Blood Retinal Barrier in Patients with Retinal Detachment and Protects Against Retinal Degeneration in an Ex Vivo Model.
Daruich, Alejandra; Jaworski, Thara; Henry, Hugues; Zola, Marta; Youale, Jenny; Parenti, Léa; Naud, Marie-Christine; Delaunay, Kimberley; Bertrand, Mathilde; Berdugo, Marianne; Kowalczuk, Laura; Boatright, Jeffrey; Picard, Emilie; Behar-Cohen, Francine.
Affiliation
  • Daruich A; Centre de Recherche des Cordeliers INSERM, UMRS1138, Team 17, Université de Paris, Université Sorbonne Paris Cité, Paris, France.
  • Jaworski T; Ophthalmology Department, Necker-Enfants Malades University Hospital, AP-HP, Paris, France.
  • Henry H; Ophthalmology Department, University of Lausanne, Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, Lausanne, Switzerland.
  • Zola M; Centre de Recherche des Cordeliers INSERM, UMRS1138, Team 17, Université de Paris, Université Sorbonne Paris Cité, Paris, France.
  • Youale J; Innovation and Development Laboratory, Clinical Chemistry Service, Lausanne University Hospital, Lausanne, Switzerland.
  • Parenti L; Ophthalmology Department, University of Lausanne, Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, Lausanne, Switzerland.
  • Naud MC; Centre de Recherche des Cordeliers INSERM, UMRS1138, Team 17, Université de Paris, Université Sorbonne Paris Cité, Paris, France.
  • Delaunay K; Centre de Recherche des Cordeliers INSERM, UMRS1138, Team 17, Université de Paris, Université Sorbonne Paris Cité, Paris, France.
  • Bertrand M; Centre de Recherche des Cordeliers INSERM, UMRS1138, Team 17, Université de Paris, Université Sorbonne Paris Cité, Paris, France.
  • Berdugo M; Centre de Recherche des Cordeliers INSERM, UMRS1138, Team 17, Université de Paris, Université Sorbonne Paris Cité, Paris, France.
  • Kowalczuk L; Institut du Cerveau et de la Moelle épinière (ICM), INSERM, CNRS, AP-HP, Sorbonne Université, Pitié-Salpêtrière University Hospital, Paris, France.
  • Boatright J; Centre de Recherche des Cordeliers INSERM, UMRS1138, Team 17, Université de Paris, Université Sorbonne Paris Cité, Paris, France.
  • Picard E; Ophthalmology Department, University of Lausanne, Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, Lausanne, Switzerland.
  • Behar-Cohen F; Ophthalmology Department, Emory University School of Medicine, Atlanta, GA, USA.
Neurotherapeutics ; 18(2): 1325-1338, 2021 04.
Article in En | MEDLINE | ID: mdl-33537951
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Retina / Retinal Degeneration / Ursodeoxycholic Acid / Retinal Detachment / Cholagogues and Choleretics / Blood-Retinal Barrier / Apoptosis / Retinal Cone Photoreceptor Cells Type of study: Clinical_trials Limits: Animals / Female / Humans / Male / Middle aged Language: En Journal: Neurotherapeutics Journal subject: NEUROLOGIA Year: 2021 Document type: Article Affiliation country: France Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Retina / Retinal Degeneration / Ursodeoxycholic Acid / Retinal Detachment / Cholagogues and Choleretics / Blood-Retinal Barrier / Apoptosis / Retinal Cone Photoreceptor Cells Type of study: Clinical_trials Limits: Animals / Female / Humans / Male / Middle aged Language: En Journal: Neurotherapeutics Journal subject: NEUROLOGIA Year: 2021 Document type: Article Affiliation country: France Country of publication: United States