Human Interphotoreceptor Matrix Contains Serum Albumin and Retinol-binding Protein

Adler, Alice J.; Edwards, Ross B.

doi:10.1006/exer.1999.0780

Cited by 47 publications

(43 citation statements)

References 30 publications

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“…Rbp4 is expressed in the retinal pigment epithelium. [26][27][28][29] However, little is known about the function of RBP4 in the eye. Quadro et al 30 generated a transgenic mouse strain (hRBP4: mRbp4 − / − ) that expressed human RBP4 under the control of the muscle creatine kinase promoter in the Rbp4 − / − background.…”

Section: Discussionmentioning

confidence: 99%

Severe ocular phenotypes in Rbp4-deficient mice in the C57BL/6 genetic background

Shen

Shi

Suzuki

et al. 2016

Laboratory Investigation

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Retinol-binding protein 4 (RBP4) is a specific carrier for retinol in the blood. In hepatocytes, newly synthesized RBP4 associates with retinol and transthyretin and is secreted into the blood. The ternary transthyretin-RBP4-retinol complex transports retinol in the circulation and delivers it to target tissues. Rbp4-deficient mice in a mixed genetic background (129xC57BL/6J) have decreased sensitivity to light in the b-wave amplitude on electroretinogram. Sensitivity progressively improves and approaches that of wild-type mice at 24 weeks of age. In the present study, we produced Rbp4-deficient mice in the C57BL/6 genetic background. These mice displayed more severe phenotypes. They had decreased a-and b-wave amplitudes on electroretinograms. In accordance with these abnormalities, we found structural changes in these mice, such as loss of the peripheral choroid and photoreceptor layer in the peripheral retinas. In the central retinas, the distance between the inner limiting membrane and the outer plexiform layer was much shorter with fewer ganglion cells and fewer synapses in the inner plexiform layer. Furthermore, ocular developmental defects of retinal depigmentation, optic disc abnormality, and persistent hyaloid artery were also observed. All these abnormalities had not recovered even at 40 weeks of age. Our Rbp4-deficient mice accumulated retinol in the liver but it was undetectable in the serum, indicating an inverse relation between serum and liver retinol levels. Our results suggest that RBP4 is critical for the mobilization of retinol from hepatic storage pools, and that such mobilization is necessary for ocular development and visual function.

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Section: Discussionmentioning

confidence: 99%

Severe ocular phenotypes in Rbp4-deficient mice in the C57BL/6 genetic background

Shen

Shi

Suzuki

et al. 2016

Laboratory Investigation

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“…Given the seeming importance of IRBP in the bidirectional flow of retinoids between photoreceptors and RPE, it is surprising that mice with a knockout mutation in the irbp gene exhibit only slight slowing of rhodopsin regeneration after a bright flash (69,70). This retinoid transport may be due to the presence of other retinoid-binding proteins in the IPM such as retinol-binding protein (RBP) (19).…”

Section: Oxidation Of 11-cis-rol To 11-cis-ralmentioning

confidence: 99%

Diseases Caused by Defects in the Visual Cycle: Retinoids as Potential Therapeutic Agents

Travis

Golczak

Moise

et al. 2007

Annu. Rev. Pharmacol. Toxicol.

370

452

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Absorption of a photon by an opsin pigment causes isomerization of the chromophore from 11-cisretinaldehyde to all-trans-retinaldehyde. Regeneration of visual chromophore following light exposure is dependent on an enzyme pathway called the retinoid or visual cycle. Our understanding of this pathway has been greatly facilitated by the identification of disease-causing mutations in the genes coding for visual cycle enzymes. Defects in nearly every step of this pathway are responsible for human-inherited retinal dystrophies. These retinal dystrophies can be divided into two etiologic groups. One involves the impaired synthesis of visual chromophore. The second involves accumulation of cytotoxic products derived from all-trans-retinaldehyde. Gene therapy has been successfully used in animal models of these diseases to rescue the function of enzymes involved in chromophore regeneration, restoring vision. Dystrophies resulting from impaired chromophore synthesis can also be treated by supplementation with a chromophore analog. Dystrophies resulting from the accumulation of toxic pigments can be treated pharmacologically by inhibiting the visual cycle, or limiting the supply of vitamin A to the eyes. Recent progress in both areas provides hope that multiple inherited retinal diseases will soon be treated by pharmaceutical intervention.

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“…1, using the independently determined parameters for steps A, B, and C. The concentration of retinol, ROL(t) in the outer segment after rhodopsin bleaching is given by (11) with…”

Section: Data Analysis and Kinetic Modelsmentioning

confidence: 99%

Interphotoreceptor Retinoid-Binding Protein Is the Physiologically Relevant Carrier That Removes Retinol from Rod Photoreceptor Outer Segments

Blakeley

Cornwall

et al. 2007

Biochemistry

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Light detection by vertebrate rod photoreceptor outer segments results in the destruction of the visual pigment, rhodopsin, as its retinyl moiety is photoisomerized from 11-cis to all-trans. The regeneration of rhodopsin is necessary for vision and begins with the release of the all-trans retinal and its reduction to all-trans retinol. Retinol is then transported out of the rod outer segment for further processing. We used fluorescence imaging to monitor retinol fluorescence and quantify the kinetics of its formation and clearance after rhodopsin bleaching in the outer segments of living isolated frog (Rana pipiens) rod photoreceptors. We independently measured the release of all-trans retinal from bleached rhodopsin in frog rod outer segment membranes and the rate of all-trans retinol removal by the lipophilic carriers interphotoreceptor retinoid binding protein (IRBP) and serum albumin. We find that the kinetics of all-trans retinol formation in frog rod outer segments after rhodopsin bleaching are to a good first approximation determined by the kinetics of all-trans retinal release from the bleached pigment. For the physiological concentrations of carriers, the rate of retinol removal from the outer segment is determined by the IRBP concentration, while the effect of serum albumin is negligible. The results indicate the presence of a specific interaction between IRBP and rod outer segment, probably mediated by a receptor. The effect of different concentrations of IRBP on the rate of retinol removal shows no cooperativity and has an EC 50 of 40 μmol/L.The vertebrate cells responsible for vision are the rod and cone photoreceptors of the retina that convert incoming light to an electrical signal. This conversion takes place in the photoreceptor outer segments, which are full of membrane disks containing the visual pigment, and, in a physiologically important arrangement, are enveloped by the retinal pigment epithelium (RPE). The visual pigment is composed of a chromophore, 11-cis retinal, attached to an integral membrane protein, opsin. The detection of light begins with the absorption of incoming photons by the visual pigment. An absorbed photon isomerizes the chromophore † Supported by NIH/NEI grants EY14850 (YK), EY04939 (RKC) , NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript moiety from 11-cis to all-trans bringing about a conformational change that initiates a cascade of reactions culminating in membrane potential change. The recovery of the cell from light involves the deactivation of the intermediates activated by light, and the reestablishment of membrane potential (1,2). However, the isomerized chromophore, all-trans retinal, remains. For vision to be possible, it is essential that the visual pigment regenerate: that is, the alltrans retinal has to be removed, and fresh 11-cis retinal has to be provided to combine with opsin and reform the visual pigment. The reactions regenerating the pigment are known as the Visual Cycle (3-5).In the case of the rod photoreceptors, t...

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Human Interphotoreceptor Matrix Contains Serum Albumin and Retinol-binding Protein

Cited by 47 publications

References 30 publications

Severe ocular phenotypes in Rbp4-deficient mice in the C57BL/6 genetic background

Severe ocular phenotypes in Rbp4-deficient mice in the C57BL/6 genetic background

Diseases Caused by Defects in the Visual Cycle: Retinoids as Potential Therapeutic Agents

Interphotoreceptor Retinoid-Binding Protein Is the Physiologically Relevant Carrier That Removes Retinol from Rod Photoreceptor Outer Segments

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