Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Restoration of cone vision in a mouse model of achromatopsia

Nature Medicine volume 13, pages 685–687 (2007)Cite this article

Abstract

Loss of cone function in the central retina is a pivotal event in the development of severe vision impairment for many prevalent blinding diseases. Complete achromatopsia is a genetic defect resulting in cone vision loss in 1 in 30,000 individuals. Using adeno-associated virus (AAV) gene therapy, we show that it is possible to target cones and rescue both the cone-mediated electroretinogram response and visual acuity in the Gnat2cpfl3 mouse model of achromatopsia.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Cone targeting and rescue of the light-adapted ERG response in Gnat2cpfl3 mice.
Figure 2: Rescue of visual acuity in Gnat2cpfl3 mice.

Similar content being viewed by others

Article 06 February 2020

Stylianos E. Antonarakis, Brian G. Skotko, … Roger H. Reeves

References

  1. Kohl, S. et al. Eur. J. Hum. Genet. 13, 302–308 (2005).

    Article  CAS  Google Scholar 

  2. Kohl, S. et al. Am. J. Hum. Genet. 71, 422–425 (2002).

    Article  CAS  Google Scholar 

  3. Johnson, S. et al. J. Med. Genet. 41, e20 (2004).

    Article  CAS  Google Scholar 

  4. Chang, B. et al. Invest. Ophthalmol. Vis. Sci. 47, 5017–5021 (2006).

    Article  Google Scholar 

  5. Deeb, S.S. Vis. Neurosci. 21, 191–196 (2004).

    Article  Google Scholar 

  6. Wang, Y. et al. Neuron 9, 429–440 (1992).

    Article  CAS  Google Scholar 

  7. Shaaban, S.A. et al. Invest Ophthalmol. Vis. Sci. 39, 1036–1043 (1998).

    CAS  PubMed  Google Scholar 

  8. Nathans, J. et al. Science 245, 831–838 (1989).

    Article  CAS  Google Scholar 

  9. Smallwood, P.M., Wang, Y. & Nathans, J. Proc. Natl. Acad. Sci. USA 99, 1008–1011 (2002).

    Article  CAS  Google Scholar 

  10. Roca, A., Shin, K.J., Liu, X., Simon, M.I. & Chen, J. Neuroscience 129, 779–790 (2004).

    Article  CAS  Google Scholar 

  11. Douglas, R.M. et al. Vis. Neurosci. 22, 677–684 (2005).

    Article  CAS  Google Scholar 

  12. Umino, Y. et al. Proc. Natl. Acad. Sci. USA 103, 19541–19545 (2006).

    Article  CAS  Google Scholar 

  13. Zhu, X. et al. Mol. Vis. 8, 462–471 (2002).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank J. Nathans (Johns Hopkins University-Howard Hughes Medical Institute) for providing the pR2.1-LacZ plasmid; C.M. Craft (Mary D. Allen Laboratories-University of Southern California Keck School of Medicine) for providing mouse cone arrestin polyclonal antibody (Luminaire Junior, mCAR/LUMIj); V. Chiodo, T. Doyle, M. Ding, I. Elder, R. Hafler, J. Pan, D. Smith and S.E. Boye for technical assistance; and G. Schultz and A. Lewin for comments on the manuscript. This research is supported by the US National Institutes of Health (EY011123, EY008571 and NS36302 to W.W.H.; EY00667 to R.B.B.; EY007758 to B.C.; and EY017246 to D.E.), the Foundation for Fighting Blindness, the Juvenile Diabetes Research Foundation, the Macula Vision Research Foundation, the Lions of Central New York, Research to Prevent Blindness, Fight for Sight and NASA. J.J.A. is supported by a US National Institutes of Health National Eye Institute training grant (EY007132).

Author information

Author notes

  1. Adrian M Timmers

    Present address: Present address: Alcon Research Ltd., Fort Worth, Texas 76134, USA.,

Authors and Affiliations

  1. Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, 32610, Florida, USA

    John J Alexander & William W Hauswirth

  2. Department of Ophthalmology, Center for Vision Research, State University of New York Upstate Medical University, Syracuse, 13210, New York, USA

    Yumiko Umino, Drew Everhart & Robert B Barlow

  3. The Jackson Laboratory, Bar Harbor, 04609, Maine, USA

    Bo Chang & Norman L Hawes

  4. Department of Ophthalmology, University of Florida College of Medicine, Gainesville, 32610, Florida, USA

    Seok H Min, Qiuhong Li, Adrian M Timmers, Ji-jing Pang & William W Hauswirth

Authors
  1. John J Alexander
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yumiko Umino
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Drew Everhart
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bo Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Seok H Min
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Qiuhong Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Adrian M Timmers
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Norman L Hawes
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ji-jing Pang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Robert B Barlow
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. William W Hauswirth
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

J.J.A. contributed to the design, execution and analysis of all of the experiments, and to manuscript writing. Y.U. contributed to the design and analysis of the behavioral tests. D.E. contributed to the execution and analysis of behavioral and paired-flash ERG tests. B.C. identified and characterized the Gnat2cpfl3 mutation. S.H.M. and A.M.T. performed the subretinal injections. Q.L. contributed to the AAV-PR2.1 promoter studies. N.L.H. contributed to the characterization of the Gnat2cpfl3 mouse. J.P. contributed to establishing the mouse colony. R.B.B. contributed to the implementation of behavioral and paired-flash ERG techniques. W.W.H. contributed to the design and analysis of all the experiments, and to manuscript writing.

Corresponding author

Correspondence to William W Hauswirth.

Ethics declarations

Competing interests

W.W.H. and the University of Florida have a financial interest in the use of rAAV therapies, and own equity in a company (AGTC Inc.) that might, in the future, commercialize some aspects of this work. All remaining authors declare that they have no competing financial interests.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Alexander, J., Umino, Y., Everhart, D. et al. Restoration of cone vision in a mouse model of achromatopsia. Nat Med 13, 685–687 (2007). https://doi.org/10.1038/nm1596

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nm1596

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing