Abstract
Purpose: :
Cone photoreceptors function in daylight conditions and depend on a constant supply of 11-cis retinal for normal function and survival. The visual cycle is responsible for supplying 11-cis retinal to photoreceptors. The Interphotoreceptor Retinoid Binding Protein (IRBP) is the most abundant protein in of the interphotoreceptor matrix (IPM) and is thought to be important in the visual cycle. IRBP binds 11-cis retinal and all-trans retinol endogenously and promotes the release of all-trans retinol from rods. However, the rod visual cycle has been shown to be intact in IRBP-/- mice, and rods are able to regenerate pigment at rates equivalent to wild-type. The goal of our current work is to characterize the cone visual system in IRBP-/- mice, and we hypothesize that cone function is impaired in the absence of IRBP.
Methods: :
Photopic electroretinograms (ERGs) were used to analyze cone function in IRBP-/- mice with increasing age (2 months to 1 year). Photopic intensity-response curves were constructed on 2 month old IRBP-/- mice (n=8) before and after the injection of 9-cis retinal.
Results: :
The rod and cone ERGs of IRBP-/- mice are depressed relative to wild-type at all ages. The rod response is remarkably stable in aging IRBP-/- mice but shows some decline at higher intensities. However, the cone response does not decline with age and remains stable through 1 year. Injection of 9-cis retinal resulted in an average response increase of 50% (range of 30% to 90%) at all intensities to levels approaching the wild-type response. No changes are seen in rods after 9-cis injection.
Conclusions: :
In IRBP-/- mice, the cone response is depressed relative to wild-type mice but, unlike rods, does not appear to decline with age. With 9-cis retinal injections, the cone response of IRBP-/- mice recovers to near wild-type levels, indicating that cone opsin is present. Our results indicate that the cones of IRBP-/- mice survive in a retinoid deficient state with more un-regenerated cone opsin than wild-type mice. This suggests that IRBP is essential to the cone visual cycle and the normal function of cones.
Keywords: retinoids/retinoid binding proteins • photoreceptors • electroretinography: non-clinical