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Co-Expression of Wild-Type and Mutant S163R C1QTNF5 in Retinal Pigment Epithelium

  • Astra DinculescuEmail author
  • Frank M. Dyka
  • Seok-Hong Min
  • Rachel M. Stupay
  • Marcus J. Hooper
  • W. Clay Smith
  • William W. Hauswirth
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1074)

Abstract

The pathogenic mutation S163R in C1QTNF5 causes a disorder known as autosomal dominant late-onset retinal degeneration (L-ORD), characterized by the presence of thick extracellular sub-RPE deposits, similar histopathologically to those found in AMD patients. We have previously shown that the S163R C1QTNF5 mutant forms globular aggregates within the RPE in vivo following its AAV-mediated expression in the RPE and exhibits a reversely polarized distribution, being routed toward the basal rather than apical RPE. We show here that when both wild-type and mutant S163R C1QTNF5 are simultaneously delivered subretinally to mouse RPE cells, the mutant impairs the wild-type protein secretion from the RPE, and both proteins are dispersed toward the basal and lateral RPE membrane. This result has mechanistic and therapeutic implications for L-ORD disorder.

Keywords

RPE Basal laminar deposit AMD Late-onset retinal degeneration C1QTNF5 AAV Protein aggregation 

Notes

Acknowledgments

This study was supported in part by an unrestricted grant from Research to Prevent Blindness, NIH grants EY021721 and EY018331, FFB, and MVRF.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Astra Dinculescu
    • 1
    Email author
  • Frank M. Dyka
    • 1
  • Seok-Hong Min
    • 1
  • Rachel M. Stupay
    • 1
  • Marcus J. Hooper
    • 1
  • W. Clay Smith
    • 1
  • William W. Hauswirth
    • 1
  1. 1.Department of OphthalmologyCollege of Medicine, University of FloridaGainesvilleUSA

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