DOCOSAHEXAENOIC ACID MODULATES THE INTERACTIONS OF THE INTERPHOTORECEPTOR RETINOID-BINDING PROTEIN WITH 11-CIS-RETINAL

Rapid transport of retinoids across the interphotoreceptor matrix is a critical part of the visual cycle, since it serves to replenish bleac hed rhodopsin with its chromophore 11-cis-retinal. The transport of re tinoids in the interphotoreceptor matrix is believed to be mediated by the interphotoreceptor retinoid-binding protein (IRBP), a protein tha t, in addition to possessing two retinoid-binding sites, associates in vivo with long chain fatty acids. Here, the interrelationships betwee n binding of the two types of ligands to IRBP were studied, The compos ition of fatty acids associated with IRBP in bovine retina was determi ned, and it was found that polyunsaturated fatty acids constitute a si gnificant fraction of those, It was further found that docosahexaenoic acid, but not palmitic acid, induced a rapid and specific release of 11-cis-retinal from one of the protein's retinoid-binding sites, Based on these results and on the additional observation that a steep conce ntration gradient of docosahexaenoic acid exists between photoreceptor and pigment epithelium cells, a model for the mechanism by which IRBP may target 11-cis-retinal to photoreceptor cells is proposed.