September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Long-term photoreceptor rescue in two rodent models of retinitis pigmentosa by
adeno-associated virus delivery of Stanniocalcin-1
Author Affiliations & Notes
  • Gavin W Roddy
    Department of Ophthalmology, Mayo School of Graduate Medical Education, Rochester, Minnesota, United States
  • Douglas Yasumura
    Ophthalmology, University of California, San Francisco, California, United States
  • Michael Matthes
    Ophthalmology, University of California, San Francisco, California, United States
  • Marcel Victor Alavi
    Ophthalmology, University of California, San Francisco, California, United States
  • Sanford L. Boye
    Ophthalmology, University of Florida, Gainesville, Florida, United States
  • Michael P Fautsch
    Department of Ophthalmology, Mayo School of Graduate Medical Education, Rochester, Minnesota, United States
  • William W Hauswirth
    Ophthalmology, University of Florida, Gainesville, Florida, United States
  • Matthew LaVail
    Ophthalmology, University of California, San Francisco, California, United States
  • Footnotes
    Commercial Relationships   Gavin Roddy, None; Douglas Yasumura, None; Michael Matthes, None; Marcel Alavi, None; Sanford Boye, None; Michael Fautsch, None; William Hauswirth, AGTC (P), AGTC (F), AGTC (C); Matthew LaVail, None
  • Footnotes
    Support  Mayo Research Foundation, R24EY022023, EY001919, EY006842, Foundation Fighting Blindness
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 2737. doi:
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    • Get Citation

      Gavin W Roddy, Douglas Yasumura, Michael Matthes, Marcel Victor Alavi, Sanford L. Boye, Michael P Fautsch, William W Hauswirth, Matthew LaVail; Long-term photoreceptor rescue in two rodent models of retinitis pigmentosa by
      adeno-associated virus delivery of Stanniocalcin-1. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2737.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Retinal degenerations, including atrophic age-related macular degeneration and the retinitis pigmentosa family of diseases, are lacking in therapies. We recently identified Stanniocalcin-1 (STC-1) as a potential novel treatment for retinal degeneration. Following intravitreal injection of recombinant human STC-1, we observed molecular, histologic, and functional rescue of retinal degeneration in the Royal College of Surgeons and S334ter-3 models of retinitis pigmentosa. In the present study, to evaluate longer-term rescue, we delivered STC-1 by utilizing an adeno-associated viral construct (AAV).

Methods : AAV2(trpYF mut)-hSyn1-hSTC1-Flag (AAV-STC-1) was generated and 2 µL was delivered intravitreally in one eye of either P23H-1 or S334ter-4 hemizygote rhodopsin transgenic rats. Animals were treated at post-natal day 10 (P10) or 19 (P19) and sacrificed at P120 for tissue analysis. In a cohort of animals, electroretinography was performed at P120. To assess molecular changes, total RNA was isolated and microarray analysis and quantitative real-time PCR were performed.

Results : Gene expression analysis revealed that STC-1 was upregulated 40-fold in the P23H and 300-fold in the S334ter-4 at P120 following treatment with AAV-STC-1. Both P23H-1 and S334ter-4 rhodopsin transgenic rats showed significant photoreceptor preservation compared to the contralateral uninjected control eye as assessed by outer nuclear layer thickness. Electroretinographic analysis in P23H-1 animals injected with AAV-STC-1 showed significantly increased scotopic b-wave and photopic b-wave; however, no changes in ERG response amplitudes were observed in S334ter-4 animals treated with AAV-STC-1. Microarray analysis revealed a total of 49 genes upregulated by >2-fold in both P23H-1 and S334ter-4 rats treated with AAV-STC-1. Quantitative PCR confirmed upregulation of Hspb1 (Hspb27), Serpinf1 (PEDF), and Nupr1 in the S334ter-4 model.

Conclusions : AAV mediated expression of STC-1 delayed photoreceptor degeneration in two rodent models of retinitis pigmentosa. Candidate genes were identified for future studies to address mechanism of action and therapeutic potential.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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