title: Carotenoids as possible interphotoreceptor retinoid-binding protein (IRBP) ligands: a surface plasmon resonance (SPR) based study.
abstract: Uptake, transport and stabilization of xanthophylls in the human retina are important components of a complex multistep process that culminates in a non-uniform distribution of these important nutrients in the retina. The process is far from understood; here, we consider the potential role of interphotoreceptor retinoid-binding protein (IRBP) in this process. IRBP is thought to facilitate the exchange of 11-cis-retinal, 11-cis-retinol and all-trans-retinol between the retinal pigment epithelium (RPE), photoreceptors and Müller cells in the visual cycle. Structural and biochemical studies suggest that IRBP has a variety of nonequivalent ligand binding sites that function in this process. IRBP is multifunctional, being able to bind a variety of physiologically significant molecules including fatty acids in the subretinal space. This wide range of binding activities is of particular interest because it is unknown whether the lutein and zeaxanthin found in the macula originate from the choroidal or retinal circulations. If from the choroidal circulation, then IRBP is a likely mediator for their transport across the interphotoreceptor matrix. In this report, we explore the binding interactions of retinoids, fatty acids, and carotenoids with IRBP using surface plasmon resonance (SPR)-based biosensors. IRBP showed similar affinity toward retinoids and carotenoids (1-2 μM), while fatty acids had approximately 10 times less affinity. These results suggest that further studies should be carried out to evaluate whether IRBP has a physiologically relevant role in binding lutein and zeaxanthin in the interphotoreceptor matrix.
authors.affiliation: Moran Eye Center, University of Utah School of Medicine, 65 Mario Capecchi Drive, Salt Lake City, UT 84132, United States.
authors.forename: Preejith P
authors.initials: PP
authors.lastname: Vachali
authors.forename: Brian M
authors.initials: BM
authors.lastname: Besch
authors.forename: Federico
authors.initials: F
authors.lastname: Gonzalez-Fernandez
authors.forename: Paul S
authors.initials: PS
authors.lastname: Bernstein
mesh_terms: D000818:Animals; D015374:Biosensing Techniques / Q000379:methods; D002338:Carotenoids / Q000737:chemistry / Q000378:metabolism*; D002417:Cattle; D005136:Eye Proteins / Q000737:chemistry* / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008024:Ligands; D011485:Protein Binding / Q000502:physiology; D012177:Retinol-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D020349:Surface Plasmon Resonance / Q000379:methods*; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D002338:Carotenoids; D005136:Eye Proteins; D005230:Fatty Acids, Nonesterified; D008024:Ligands; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial
keywords: Carotenoids; Interphotoreceptor matrix; Interphotoreceptor retinoid-binding protein; Macular pigments; Retinoids; Surface plasmon resonance