Beschreibung:
<jats:p>The first event in light perception is absorption of a photon by the retinaldehyde chromophore of an opsin pigment in a rod or cone photoreceptor cell. This induces isomerization of the chromophore, rendering the bleached pigment insensitive to light. Restoration of light sensitivity requires chemical reisomerization of retinaldehyde via a multistep enzyme pathway, called the visual cycle, in cells of the retinal pigment epithelium (RPE). Interphotoreceptor retinoid-binding protein (IRBP) is present in the extracellular space between photoreceptors and the RPE. IRBP is known to bind visual retinoids. Previous studies on<jats:italic>irbp</jats:italic><jats:sup>−/−</jats:sup>mice suggested that IRBP plays an insignificant role in opsin-pigment regeneration. However, the mice in these studies were uncontrolled for a severe mutation in the<jats:italic>rpe65</jats:italic>gene. Rpe65 catalyzes the rate-limiting step in the visual cycle. Here, we examined the phenotype in<jats:italic>irbp</jats:italic><jats:sup>−/−</jats:sup>mice homozygous for the wild-type (Leu450)<jats:italic>rpe65</jats:italic>gene. We show that lack of IRBP causes delayed transfer of newly synthesized chromophore from RPE to photoreceptors. Removal of bleached chromophore from photoreceptors is also delayed in<jats:italic>irbp</jats:italic><jats:sup>−/−</jats:sup>retinas after light exposure. It was previously shown that rods degenerate in<jats:italic>irbp</jats:italic><jats:sup>−/−</jats:sup>mice. Here, we show that cones and rods degenerate at similar rates. However, cones are more affected functionally and show greater reductions in outer segment length than rods in<jats:italic>irbp</jats:italic><jats:sup>−/−</jats:sup>mice. The disproportionate reductions in cone function and outer-segment length appear to result from mistrafficking of cone opsins due to impaired delivery of retinaldehyde chromophore, which functions as a chaperone for cone opsins but not rhodopsin.</jats:p>