Centre de Recherche des Cordeliers INSERM, UMRS1138, Team 17, Université de Paris, Université Sorbonne Paris Cité, Paris, France.
Ophthalmology Department, Necker-Enfants Malades University Hospital, AP-HP, Paris, France.
Neurotherapeutics. 2021 Apr;18(2):1325-1338. doi: 10.1007/s13311-021-01009-6. Epub 2021 Feb 3.
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.
孔源性视网膜脱离（RD）是一种威胁视力的疾病，也是视网膜变性的人类疾病模型。尽管成功地进行了复位手术，但由于视网膜下液的积聚和随后的光感受器细胞死亡，视力并未完全恢复，其机制与视网膜变性疾病的机制相似。亲水性胆酸在动物模型中具有神经保护作用，但它们是否可以口服用于治疗眼部疾病尚不清楚。熊去氧胆酸（UDCA）已被批准用于临床（例如，用于胆汁淤积），我们评估了口服 UDCA 在 RD 手术前给药的眼部生物利用度。眼部介质中 UDCA 的水平与血视网膜屏障破坏的程度相关，通过脱离的程度和视网膜下液中的白蛋白浓度来评估。在 RD 的离体模型（大鼠视网膜外植体）中，眼部介质中测量到的 UDCA 水平可保护光感受器免于凋亡和坏死。与对照患者的视网膜下液相比，从接受 UDCA 治疗的患者在手术期间收集的视网膜下液可显著保护大鼠视网膜外植体免于细胞死亡。视网膜的全转录组分析表明，UDCA 上调了抗凋亡、抗氧化和抗炎基因。口服 UDCA 可能是 RD 和其他视网膜变性疾病的潜在神经保护辅助治疗方法，应在临床试验中进一步评估。
