Interphotoreceptor retinol-binding proteins: possible transport vehicles between compartments of the retina

Lai, Yin-Lok; Wiggert, Barbara; Liu, Y. P.; Chader, Gerald J.

doi:10.1038/298848a0

Cited by 144 publications

(52 citation statements)

References 14 publications

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“…The retina was gently removed from the posterior hemisphere, and the vitreal cavity of the resulting "RPE-eyecup" (15) was washed 20 times with 1 ml of Ringer's. ROS purified by sucrose flotation (18) 10 tridecyl ether] and supplemented with hydroxylamine (final concentration, 100 mM). Absorbance spectra (Perkin-Elmer Lambda-7 spectrophotometer) recorded before and after intense irradiation were used to determine the hydroxylamine difference spectrum of the sample (6); the concentration of rhodopsin was determined from the absorbance difference at 500 nm (AA50), using an extinction coefficient of 42,000 M-1'cm-l (19).…”

Section: Methodsmentioning

confidence: 99%

“…Although it is clear that the 11-cis configuration of the retinoid is formed within the RPE (3)(4)(5)(6)(7)(8)(9), neither the identity of the 11-cis retinoid returned from the RPE to the photoreceptors nor the mode of intercellular transfer has been firmly established. Also uncertain is the role in this process of interphotoreceptor retinoid-binding protein (IRBP), a soluble protein that readily binds different chemical and isomeric forms of retinoid and is uniquely localized to the interphotoreceptor matrix compartment that separates the retina and the apical surface of the RPE (10)(11)(12)(13)(14).…”

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confidence: 99%

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Interphotoreceptor retinoid-binding protein promotes rhodopsin regeneration in toad photoreceptors.

Okajima

Pepperberg

Ripps

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

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Interphotoreceptor retinoid-binding protein (IRBP) has been hypothesized to function as an intercellular shuttle in the vertebrate eye, serving to transport retinoids between the retinal pigment epithelium (RPE) and photoreceptors in the process by which visual pigment is regenerated after photolysis. This hypothesis was tested in preparations utilizing the toad (Bufo marinus) eye and purified, initially ligand-free IRBP obtained from the bovine eye. Rod outer segments (ROS) or neural retinas were isolated and bleached, then incubated with native RPE (RPE-eyecup) in the presence or absence of IRBP. The amount of rhodopsin present after incubation was determined by spectrophotometric analysis and compared with that in control preparations receiving bovine serum albumin or Ringer's solution only. Supplementation with IRBP enhanced the formation of rhodopsin in both the ROS/RPE-eyecup and retina/RPE-eyecup preparations. Regeneration in ROS/RPE-eyecups receiving IRBP (1.8 nmol) increased in a roughly linear manner with the period of incubation (0-4 hr), at a rate of 0.44 nmol/hr. The extent of regeneration was graded with the quantities of IRBP and opsin introduced into the RPE-eyecup. With increasing amounts of IRBP (up to 5.2 nmol) or of initially available opsin (up to 15.6 nmol), the amount of rhodopsin formed (3-hr incubation) approached the same plateau value, about 2.5 nmol. Analysis of IRBP-supplemented Ringer's solution incubated in the RPEeyecup showed li-cis-retinal to be virtually the only retinoid withdrawn from the RPE. With large quantities of IRBP (3.2-9.2 nmol), the amount of 11-cis-retinal (2.7 + 0.5 nmol) withdrawn from the RPE during a 3-hr incubation was similar to the plateau value of rhodopsin formed in the ROS/ RPE-eyecup. No li-cis-retinal was observed in albuminsupplemented Ringer's solution (0.4-11.2 nmol of bovine serum albumin) or in Ringer's alone after similar incubation in the RPE-eyecup. The results suggest that an IRBP-mediated transfer of li-cis-retinal from the RPE to the rods supports rhodopsin regeneration in vivo.The regeneration of rhodopsin in vertebrate rod photoreceptors requires the supply of 11-cis-retinal to opsin contained in the rod outer segments (ROS) (1). A dependence on the retinal pigment epithelium (RPE) was demonstrated more than a century ago by Kuhne (2), who showed that contact with the RPE is essential for the regeneration of visual pigment to take place in a previously bleached retina. Although it is clear that the 11-cis configuration of the retinoid is formed within the RPE (3-9), neither the identity of the 11-cis retinoid returned from the RPE to the photoreceptors nor the mode of intercellular transfer has been firmly established. Also uncertain is the role in this process of interphotoreceptor retinoid-binding protein (IRBP), a soluble protein that readily binds different chemical and isomeric forms of retinoid and is uniquely localized to the interphotoreceptor matrix compartment that separates the retina and the apical surface of the RPE (1...

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Interphotoreceptor retinoid-binding protein promotes rhodopsin regeneration in toad photoreceptors.

Okajima

Pepperberg

Ripps

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

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“…Several structure-function activities of fundamental importance to vision are thought to be mediated by the IPM, including visual pigment chromophore exchange, metabolite trafficking, retinal adhesion, photoreceptor alignment, and photoreceptor membrane turnover (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Because this matrix resides in such a key location and is putatively crucial in supporting photoreceptor function, additional information is required as to the identity, role, and involvement of specific IPM molecules in mediating these activities.…”

mentioning

confidence: 99%

SPACRCAN, a Novel Human Interphotoreceptor Matrix Hyaluronan-binding Proteoglycan Synthesized by Photoreceptors and Pinealocytes

Acharya¹,

Foletta²,

Lee³

et al. 2000

Journal of Biological Chemistry

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The interphotoreceptor matrix is a unique extracellular complex occupying the interface between photoreceptors and the retinal pigment epithelium in the fundus of the eye. Because of the putative supportive role in photoreceptor maintenance, it is likely that constituent molecules play key roles in photoreceptor function and may be targets for inherited retinal disease. In this study we identify and characterize SPACRCAN, a novel chondroitin proteoglycan in this matrix. SPACRCAN was cloned from a human retinal cDNA library and the gene localized to chromosome 3q11.2. Analysis of SPACRCAN mRNA and protein revealed that SPACRCAN is expressed exclusively by photoreceptors and pinealocytes. SPACRCAN synthesized by photoreceptors is localized to the interphotoreceptor matrix where it surrounds both rods and cones. The functional protein contains 1160 amino acids with a large central mucin domain, three consensus sites for glycosaminoglycan attachment, two epidermal growth factor-like repeats, a putative hyaluronan-binding motif, and a potential transmembrane domain near the C-terminal. Lectin and Western blotting indicate an M r around 400,000 before and 230,000 after chondroitinase ABC digestion. Removal of N-and O-linked oligosaccharides reduces the M r to approximately 160,000, suggesting that approximately 60% of the mass of SPACRCAN is carbohydrate. Finally, we demonstrate that SPACRCAN binds hyaluronan and propose that associations between SPACRCAN and hyaluronan may be involved in organization of the insoluble interphotoreceptor matrix, particularly as SPACRCAN is the major proteoglycan present in this matrix.

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“…It binds various isomeric and chemical forms of retinoids as well as long chain fatty acids (3)(4)(5)(6), and is believed to mediate transfer of retinoids through the IPM (3,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). IRBP possesses two retinoid-binding sites (3,8,17) that seem to be functionally distinct.…”

mentioning

confidence: 99%

Binding of Retinol in Both Retinoid-binding Sites of Interphotoreceptor Retinoid-binding Protein (IRBP) Is Stabilized Mainly by Hydrophobic Interactions

Tschanz

Noy

1997

Journal of Biological Chemistry

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Shuttling of retinoids across the interphotoreceptor matrix (IPM), 1 the extracellular space separating between retinal pigment epithelium (RPE) and photoreceptor cells in the eye, is essential for the function of the visual cycle. Rhodopsin regeneration requires transport of the visual chromophore 11-cisretinal from its site of synthesis in the RPE to photoreceptor cells. On exposure to light, rhodopsin-bound 11-cis-retinal is isomerized to all-trans-retinal, hydrolyzed from the protein, and is enzymatically reduced to all-trans-retinol. Regeneration of the visual chromophore requires movement of all-trans-retinol from photoreceptors back to the RPE for re-oxidation and isomerization (reviewed in Ref. 1). Thus, the visual cycle critically includes continuous transfer of all-trans-retinol from the photoreceptors to the RPE and of 11-cis-retinal from RPE to the neural retina. The mechanisms by which retinoids, which are poorly soluble in water, are transported through the IPM at rates that are sufficient to support visual function are not completely clear at present. It has been repeatedly suggested, however, that the interphotoreceptor retinoid-binding protein (IRBP), plays an important role in this process (reviewed in Ref.2).IRBP is a 140-kDa glycoprotein that is the major soluble protein in the IPM. It binds various isomeric and chemical forms of retinoids as well as long chain fatty acids (3-6), and is believed to mediate transfer of retinoids through the IPM (3, 7-16). IRBP possesses two retinoid-binding sites (3,8,17) that seem to be functionally distinct. The specific function of one of these sites (termed "site 1" in this article) is not clear at present but it has been shown to possess a retinoid selectivity in the order of 11-cis-retinal Ͼ all-trans-retinol Ͼ all-trans-retinal Ͼ 11-cis-retinol. The higher binding affinities for 11-cis-retinal and all-trans-retinol correspond to the physiological need to shuttle these particular retinoids across the IPM (18). It is thus conceivable that site 1 serves mainly to allow IRBP to maintain a large storage pool of these retinoid forms in the extracellular space of the IPM.The recent observations that the interactions of 11-cis-retinal with the other retinoid-binding site of IRBP ("site 2") are tightly regulated by the polyunsaturated long chain fatty acid docosahexaenoic acid (DHA), provided clues regarding the possible function of site 2. It was shown that binding of DHA to IRBP dramatically reduces the affinity of site 2 for this ligand, and facilitates the rate by which 11-cis-retinal is released from this site by about an order of magnitude (6). In contrast, DHA has very little effect on the interactions of 11-cis-retinal with site 1, or on the affinities of either site 1 or site 2 for all-transretinol (6). Further evidence indicated that DHA comprises a significant fraction of fatty acids associated with IRBP in the IPM, and that a steep concentration gradient of free DHA exists across the IPM such that the level of this fatty acid is about 8-fold higher i...

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Interphotoreceptor retinol-binding proteins: possible transport vehicles between compartments of the retina

Cited by 144 publications

References 14 publications

Interphotoreceptor retinoid-binding protein promotes rhodopsin regeneration in toad photoreceptors.

Interphotoreceptor retinoid-binding protein promotes rhodopsin regeneration in toad photoreceptors.

SPACRCAN, a Novel Human Interphotoreceptor Matrix Hyaluronan-binding Proteoglycan Synthesized by Photoreceptors and Pinealocytes

Binding of Retinol in Both Retinoid-binding Sites of Interphotoreceptor Retinoid-binding Protein (IRBP) Is Stabilized Mainly by Hydrophobic Interactions

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