Abstract
Purpose:
Investigate whether retinas of mice with impaired retinal cycles exposed to light or kept in the dark tolerate prolonged high-dose administration of the 9-cis-retinal precursor, QLT091001.
Methods:
Four- to six-week-old Lrat-/- and Rpe65-/- mice (total n=126) as well as crossbred Gnat1-/- mice lacking rod phototransduction (total n=110) were gavaged weekly for 6 months with 50 mg/ kg QLT091001, either after being kept in the dark or after bright light bleaching for 30 min/week followed by maintenance in a 12 h light ≤10 lux)/12 h dark cycle. Retinal health was monitored by spectral-domain optical coherent tomography (SD-OCT) and scanning laser ophthalmoscopy (SLO) every other month and histological, biochemical and visual functional analyses were performed at the end of the experiment. Two-photon microscopy (TPM) was used to observe retinoid-containing retinosome structures in the retinal pigmented epithelium.
Results:
Retinal thickness and morphology examined by SD-OCT were well maintained in all strains treated with QLT091001. No significant increases of fundus fluorescence were detected by SLO imaging of any strain. Accumulation of all-trans-retinyl esters varied with genetic background, types of administered compounds and lighting conditions but retinal health was not compromised. TPM imaging clearly revealed maintenance of retinosomes in the RPE of all mouse strains tested.
Conclusions:
Retinas of Lrat-/-, Rpe65-/- and crossbred Gnat1-/- mice tolerated well prolonged high-dose QLT091001 treatment.
Keywords: 696 retinal degenerations: hereditary •
701 retinal pigment epithelium •
705 retinoids/retinoid binding proteins