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Alejandra Daruich, Emilie Picard, Marta Zola, Hugues Henry, Jeffrey H Boatright, Francine F Behar-Cohen; Adjuvant ursodeoxycholic acid for retinal detachment : a potential neuroprotective therapy.. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2795. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
1) To determine whether ursodeoxycholic acid (UA) administered orally and preoperatively to retinal detachment (RD) patients can cross the blood-ocular barrier, and to assess the mean concentration reached in intraocular fluids2) To determine whether UA is neuroprotective in an ex-vivo rat model of RD at the concentrations found in patients
1) Patients presenting with RD for ≥4 days from symptom onset were prospectively included. Twenty-one patients were treated before retinal detachment surgery with UA (10mg/kg) at 4 different intervals (<5 hours, 5-8 hours, 8-11 hours and >11 hours). Five RD patients served as controls. All patients underwent pars-plana vitrectomy. Subretinal fluid and vitreous humor samples were collected during surgery. UA and total protein concentrations were measured in all samples.2) To evaluate the neuroprotective effect of UA, rat neural retinal explants were cultured in low-serum medium and treated with UA at intraocular concentration ranges ( 10, 50 and 500 ng/ml) found in patients. Markers of apoptosis (caspase 3) and Necrosis (LDH, RIP) were analyzed by western immunoblotting. Immunohistochemistry was performed on sections of fixed retinas (cone arrestin, peanut agglutinin).
1) UA was found in vitreous and/or subretinal fluid in 12 patients (57%). The concentrations of UA were higher in patients who were treated 8 hours or more before surgery. Controls patients did not present UA in subretinal fluid samples (p=0.04, vs treated patients). The UA concentration in subretinal fluid was correlated with the total protein concentration (p<0.0001).2) LDH decreased significantly in the medium of treated explants at all doses (10, 50 and 500 ng/ml) from 24 to 48 hours compared to control media (p=0.01, p=0.02, p=0.003, respectively). Caspase 3 was significantly lower in retinas treated at 10 and 50 ng/ml compared to controls (p=0.02). RIP was significantly lower in all treated retinas compared to controls (p=0.02). The number of cones (cone arrestin+) was higher at 50 and 500 ng/ml (P=0.04). The number of cones (Peanut agglutinin +) was higher at 10 ng/ml.
Following oral administartion, UA crosses the blood-ocular barrier in the disrupted state of RD eyes, and accumulates in subretinal fluid at concentrations that confer neuroprotection in an ex-vivo model of RD.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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