Purchase this article with an account.
Valerie Fontaine, Elodie Monteiro, Elena Brazhnikova, Mylene Fournie, Christine Balducci, Louis Guibout, Jose A. Sahel, Stanislas Veillet, Pierre Dilda, René Lafont; CHRONIC ORAL TREATMENT WITH BIO201 PRESERVES RETINAL FUNCTION IN A DRY AMD EXPERIMENTAL MODEL. Invest. Ophthalmol. Vis. Sci. 2018;59(9):241.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
We have recently demonstrated the potential of BIO201, a PPAR ligand entering clinical development, on retinal pigmented epithelium (RPE) and retina photoprotection in vitro and in vivo. Here we demonstrate that chronic BIO201 oral administration to a mouse model of dry AMD can slow down or stop the pathological features when used as preventive or curative treatment.
Experiments were performed using the Abca4-/-Rdh8-/- transgenic mouse model of dry AMD. Young mice (6-week-old males; n=10) were used to test BIO201 as a preventive treatment and older mice (12-month-old males, n=7 and females, n=10) to test it as a curative treatment. Mice were fed daily with BIO201 (a pharmaceutical grade norbixin) supplemented (0.5 g/kg) food or regular regimen for 5 or 6 months. Full field scotopic and photopic electroretinogram (ERG) were measured at the end of the treatment. One eye was collected for A2E measurement, and the second was used for histological analyses. Photoreceptor nuclei quantification was performed on eye cryosections. Bioavailability of BIO201 was measured in all mice by HPLC-MS/MS. Statistical analyses were performed using either a t test or a one-way ANOVA followed by Dunnett’s test.
In the preventive experiment BIO201 significantly maintained the scotopic ERG a-wave (82% vs 62% for control compared to 6 week-old mice; p<0.01). A2E accumulation was reduced by 22% (p<0.01). In the curative experiment, BIO201 completely preserved the scotopic ERG a-wave and protected most of the residual photoreceptors in females but not in males. No difference was measured for the photopic ERG after either preventive or curative treatments. The sex differences appear to be related to the mouse model itself rather than to the molecule. Old male mice showed an accelerated kinetics of age-related A2E accumulation in the eyes and a more deteriorated ERG before treatment. At 1 year of age, A2E level was higher in males compared to females (230.4 ± 11.5 vs 192.9 ± 6.3 pmol/eye, p<0.05) whereas ERG a-wave was lower (-103.3 ± 5.8 vs -115.7 ± 6.3 µV, p<0.05). Males also showed a reduced BIO201 bioavailability as compared to females.
Oral administration of BIO201 (ca. 50 mg.kg-1.d-1) provides a significant protection to the retina. These results support the clinical development of BIO201 for dry AMD prevention and treatment.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
This PDF is available to Subscribers Only