Retinoid Content, Visual Responses, and Ocular Morphology Are Compromised in the Retinas of Mice Lacking the Retinol-Binding Protein Receptor, STRA6

PURPOSE. We report generation of a mouse model in which the STRA6 gene has been disrupted functionally to facilitate the study of visual responses, changes in ocular morphology, and retinoid processing under STRA6 protein deficiency. METHODS. A null mouse line, stra6 -/-, was generated. Western Blot and immunocytochemistry were used to determine expression of STRA6 protein. Visual responses and morphological studies were performed on 6-week, 5-month and 10-month-old mice. The retinoid content of eye tissues was evaluated in dark-adapted mice by high performance liquid chromatography. RESULTS. STRA6 protein was not detectable in stra6 -/- null mice, which had a consistent reduction, but not total ablation of their visual responses. The mice also showed significant depletion of their retinoid content in retinal pigment epithelium (RPE) and neurosensory retina, including a 95% reduction in retinyl esters. At the morphological level, a reduction in thickness of the neurosensory retina due to shortening of the rod outer and inner segments was observed when compared to control litter mates with a commensurate reduction in rod a- and b-wave amplitudes. In addition, there was a reduction in cone photoreceptor cell number and cone b-wave amplitude. A typical hallmark in stra6 -/- null eyes was the presence of a persistent primary hypertrophic vitreous, an optically dense vascularized structure located in the vitreous humor between the posterior surface of the lens and neurosensory retina. CONCLUSIONS. Our studies of stra6 -/- null mice established the importance of the STRA6 protein for the uptake, intracellular transport, and processing of retinol by the RPE. In its absence, rod photoreceptor outer and inner segment length was reduced, and cone cell numbers were reduced, as were scotopic and photopic responses. STRA6 also was required for dissolution of the primary vitreous. However, it was clear from these studies that STRA6 is not the only pathway for retinol uptake by the RPE. (Invest Ophthalmol Vis Sci. 2012;53:3027-3039) DOI:10.1167/iovs.11-8476