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Endoplasmic Reticulum Stress in Vertebrate Mutant Rhodopsin Models of Retinal Degeneration

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Retinal Degenerative Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 801))

Abstract

Rhodopsin mutations cause many types of heritable retinitis pigmentosa (RP). Biochemical and in vitro studies have demonstrated that many RP-linked mutant rhodopsins produce misfolded rhodopsin proteins, which are prone to aggregation and retention within the endoplasmic reticulum, where they cause endoplasmic reticulum stress and activate the Unfolded Protein Response signaling pathways. Many vertebrate models of retinal degeneration have been created through expression of RP-linked rhodopsins in photoreceptors including, but not limited to, VPP/GHL mice, P23H Rhodopsin frogs, P23H rhodopsin rats, S334ter rhodopsin rats, C185R rhodopsin mice, T17M rhodopsin mice, and P23H rhodopsin mice. These models have provided many opportunities to test therapeutic strategies to prevent retinal degeneration and also enabled in vivo investigation of cellular and molecular mechanisms responsible for photoreceptor cell death. Here, we examine and compare the contribution of endoplasmic reticulum stress to retinal degeneration in several vertebrate models of RP generated through expression of mutant rhodopsins.

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Abbreviations

RP:

Retinitis pigmentosa

ER:

Endoplasmic reticulum

UPR:

Unfolded Protein Response

VPP :

V20G, P23H, and P27L mutations

GHL :

V20G, P23H, and P27L mutations

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Acknowledgment

Supported by NIH grant EY001919, EY002162, EY006842, EY020846, and the Foundation Fighting Blindness.

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Authors and Affiliations

  1. Department of Pathology, University of California, San Diego, USA

    Heike Kroeger & Jonathan H. Lin

  2. Departments of Anatomy and Ophthalmology, University of California, San Francisco, USA

    Matthew M. LaVail

Authors
  1. Heike Kroeger
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  2. Matthew M. LaVail
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  3. Jonathan H. Lin
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Corresponding author

Correspondence to Jonathan H. Lin .

Editor information

Editors and Affiliations

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

    John D. Ash

  2. University Hospital Zurich, Zurich, Switzerland

    Christian Grimm

  3. Cole Eye Institute at the Cleveland Clin Division of Ophthalmology, Cleveland, Ohio, USA

    Joe G. Hollyfield

  4. Dean A. McGee Eye Inst., University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA

    Robert E. Anderson

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

    Matthew M. LaVail

  6. Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, USA

    Catherine Bowes Rickman

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Kroeger, H., LaVail, M., Lin, J. (2014). Endoplasmic Reticulum Stress in Vertebrate Mutant Rhodopsin Models of Retinal Degeneration. In: Ash, J., Grimm, C., Hollyfield, J., Anderson, R., LaVail, M., Bowes Rickman, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 801. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3209-8_74

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  • DOI: https://doi.org/10.1007/978-1-4614-3209-8_74

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  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-3208-1

  • Online ISBN: 978-1-4614-3209-8

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