Purpose

The neuroprotective properties of hydrophilic bile acids are recognized but whether their oral administration can benefit to patients with retinal diseases is unknown. Rhegmatogenous retinal detachment (RD) is a threatening visual condition and a human disease model for retinal degenerations. Despite surgical reattachment, vision does not fully recover, due to subretinal fluid (SFR) and photoreceptor cell death, through mechanisms that recapitulate those of retinal degenerative diseases. We have measured the ocular concentration of Ursodeoxycholic acid (UDCA) administered orally to patients with RD. We then tested the effects and mechanisms of UDCA, at concentrations found in patient’s eyes, in RD models. Finally, we analyzed the neuroprotective effects of ocular fluids from treated patients.

Methods

26 patients with RD were included. 21 patients received UDCA before surgery. Ocular fluids samples were collected and bile acids were measured. Rat retinal explants and WERI-Rb-1 human cone cell line were exposed to albumin or patient’s SRF ± UDCA. Cell death markers and transcriptome were analyzed.

Results

UDCA was detected in ocular media after oral administration and its level correlated with protein concentration in SRF and extension of RD. At 6 months after surgery, visual recovery was superior in patients who had higher UDCA ocular levels.

UDCA levels measured in human ocular media, protected photoreceptors from apoptosis and necrosis in rats retinal explants exposed to albumin and UDCA protected WERI-Rb-1 cells from albumin-induced death. Cell death was reduced in retinal explants exposed to SRF collected from UDCA-treated patients as compared to SRF from controls. UDCA effects resulted from the up-regulation of anti-apoptotic, anti-oxidant and anti-inflammatory genes.

Conclusions

Oral UDCA reaches neuroprotective concentrations in patients with RD, showing its potential as an adjuvant to surgery but also in other retinal degenerative diseases.