Normal Function of the Cone Visual System Requires the Interphotoreceptor Retinoid Binding Protein (IRBP)

Abstract

An adequate supply of 11-cis retinal is essential to the normal function and survival of photoreceptors. Rods and cones are activated when light isomerizes 11-cis retinal to all-trans retinal, and continuous function requires the recycling of all-trans photoproducts back into 11-cis retinal. Cones mediate color vision and are the daytime photoreceptors most important for human vision, and their ability to function in constant light may be linked to a novel cone-specific visual cycle. The interphotoreceptor retinoid-binding protein (IRBP) is a proposed retinoid transporter in the visual cycle, but retinoid metabolism in the rods of Irbp-/- mice is surprisingly normal. Our goal was to analyze the cone population in Irbp-/- mice and explore IRBP's contribution to normal cone function. Irbp-/- mice have cone densities equivalent to C57Bl/6 (WT) and express normal levels of cone opsins. However, cone function measured by electroretinogram (ERG) is reduced in Irbp-/- mice. Because a visual cycle disruptions could result in an 11-cis retinoid deficiency, cone ERGs were measured in Irbp-/- mice before and after injections of 9-cis retinal. Treatment with 9-cis retinal rescued the cone response in Irbp-/- mice, but had no effect on Irbp-/- rods or WT responses. These data show that the absence of IRBP results in an 11-cis retinal deficiency for cones but not rods and indicate that IRBP is essential to normal cone function.