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The Retinol-Binding Protein Receptor 2 (Rbpr2) Is Required for Photoreceptor Survival and Visual Function in the Zebrafish

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Retinal Degenerative Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1074))

Abstract

Vitamin A/retinol (ROL) and its metabolites (retinoids) play critical roles in eye development and photoreception. Short-term dietary vitamin A deficiency (VAD) manifests clinically as night blindness, while prolonged VAD is known to cause retinal pigment epithelium (RPE) and photoreceptor degeneration. Therefore, sustained uptake of dietary vitamin A, for ocular retinoid production, is essential for photoreceptor health and visual function. The mechanisms influencing the uptake, storage, and supply of dietary vitamin A, for ocular retinoid production, however, are not fully understood. We investigated, in zebrafish, the physiological role of the retinol-binding protein receptor 2 (Rbpr2), for the uptake of dietary ROL, which is necessary for vision. NIH3T3 cells expressing zebrafish Rbpr2 showed plasma membrane localization patterns and were capable of ROL uptake from its bound form. Using whole-mount in situ hybridization, Rbpr2 was found to be expressed exclusively in the liver, intestine, and pancreas, of staged zebrafish larvae. At 5.5 days post fertilization, TALEN-generated rbpr2 mutants (rbpr2 −/− ) had smaller eyes and shorter OS lengths and showed loss of PNA (cones) and rhodopsin (rods) by immunofluorescence staining. Finally, tests for visual function using optokinetic response (OKR) showed no consistent OKR in rbpr2 −/− larval zebrafish. Our analysis, therefore, suggests that Rbpr2 is capable of ROL uptake and loss of this membrane receptor in zebrafish results in photoreceptor defects that adversely affect visual function.

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Abbreviations

(11-cis-RAL):

11-cis-retinaldehyde

PRL:

Photoreceptor cell layer

RBP4:

Retinol-binding protein 4

Rbpr2:

Retinol-binding protein receptor 2

ROL:

All-trans retinol

RPE:

Retinal pigmented epithelium

SR-B1:

Scavenger receptor class B type 1

STRA6:

Stimulated by retinoic acid 6

VAD:

Vitamin A deficiency

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Acknowledgments

This study was supported by NIH grant EY025034-02 (GPL) and, in part, by a Knights Templar Eye Foundation Career-Starter Grant (GPL) and a Knights Templar Eye Foundation Career-Renewal Grant (GPL), NIH grant DK074038 (JHL), and a VA Merit award 2I01BX000820 (JHL).

Author information

Authors and Affiliations

  1. Division of Nephrology, Medical University of South Carolina, Charleston, SC, USA

    Glenn P. Lobo & Joshua H. Lipschutz

  2. Department of Ophthalmology, Medical University of South Carolina, Charleston, SC, USA

    Glenn P. Lobo

  3. Department of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA

    Gayle Pauer & Stephanie A. Hagstrom

  4. Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA

    Stephanie A. Hagstrom

Authors
  1. Glenn P. Lobo
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  2. Gayle Pauer
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  3. Joshua H. Lipschutz
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  4. Stephanie A. Hagstrom
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Corresponding author

Correspondence to Glenn P. Lobo .

Editor information

Editors and Affiliations

  1. Department of Ophthalmology, University of Florida, Gainesville, Florida, USA

    John D. Ash

  2. Ophthalmology and Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA

    Robert E. Anderson

  3. School of Medicine Beckman Vision Center, University of California San Francisco, San Francisco, California, USA

    Matthew M. LaVail

  4. Departments of Ophthalmology and Cell Biology, Duke Eye Center, Duke University Medical Center, Durham, North Carolina, USA

    Catherine Bowes Rickman

  5. Division of Ophthalmology, Case Western Reserve University, Cleveland, Ohio, USA

    Joe G. Hollyfield

  6. Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland

    Christian Grimm

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Lobo, G.P., Pauer, G., Lipschutz, J.H., Hagstrom, S.A. (2018). The Retinol-Binding Protein Receptor 2 (Rbpr2) Is Required for Photoreceptor Survival and Visual Function in the Zebrafish. In: Ash, J., Anderson, R., LaVail, M., Bowes Rickman, C., Hollyfield, J., Grimm, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 1074. Springer, Cham. https://doi.org/10.1007/978-3-319-75402-4_69

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