Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa

V. Busskamp, J. Duebel, D. Bálya, M. Fradot, T. Viney, S. Siegert, A. Groner, E. Cabuy, V. Forster, M. Seeliger, M. Biel, P. Humphries, M. Pâques, S. Mohand Saïd, D. Trono, K. Deisseroth, J. Sähel, S. Picaud, B. Roska, Science 329 (2010) 413–417.

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Abstract
Retinitis pigmentosa refers to a diverse group of hereditary diseases that lead to incurable blindness, affecting two million people worldwide. As a common pathology, rod photoreceptors die early, whereas light-insensitive, morphologically altered cone photoreceptors persist longer. It is unknown if these cones are accessible for therapeutic intervention. Here, we show that expression of archaebacterial halorhodopsin in light-insensitive cones can substitute for the native phototransduction cascade and restore light sensitivity in mouse models of retinitis pigmentosa. Resensitized photoreceptors activate all retinal cone pathways, drive sophisticated retinal circuit functions (including directional selectivity), activate cortical circuits, and mediate visually guided behaviors. Using human ex vivo retinas, we show that halorhodopsin can reactivate light-insensitive human photoreceptors. Finally, we identified blind patients with persisting, light-insensitive cones for potential halorhodopsin-based therapy.
Publishing Year
Date Published
2010-07-23
Journal Title
Science
Acknowledgement
This study was supported by Friedrich Miescher Institute funds; a U.S. Office of Naval Research Naval International Cooperative Opportunities in Science and Technology Program grant; a Marie Curie Excellence grant and a European Union (EU) HEALTH-F2-223156 grant to B.R.; a grant from the EU (RETICIRC) to B.R. and S.P.; grants from the Agence nationale de la recherche (MEDINAS, RETINE) to S.P.; a Center Grant from Foundation Fighting Blindness (U.S.) to S.M.-S. and J.A.S.; grants from the Swiss National Science Foundation and the EU to D.T.; a grant from the EU (TREATRUSH) to J.A.S., S.P., and B.R.; a Marie Curie Postdoctoral Fellowship to D.B.; and a National Centers of Competence in Research Frontiers in Genetics fellowship to V.B. and A.C.G. The Ocular Genetics Unit at Trinity College Dublin is supported by Science Foundation Ireland
Volume
329
Issue
5990
Page
413 - 417
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Busskamp V, Duebel J, Bálya D, et al. Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa. Science. 2010;329(5990):413-417. doi:10.1126/science.1190897
Busskamp, V., Duebel, J., Bálya, D., Fradot, M., Viney, T., Siegert, S., … Roska, B. (2010). Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa. Science, 329(5990), 413–417. https://doi.org/10.1126/science.1190897
Busskamp, Volker, Jens Duebel, Dávid Bálya, Mathias Fradot, Tim Viney, Sandra Siegert, Anna Groner, et al. “Genetic Reactivation of Cone Photoreceptors Restores Visual Responses in Retinitis Pigmentosa.” Science 329, no. 5990 (2010): 413–17. https://doi.org/10.1126/science.1190897.
V. Busskamp et al., “Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa,” Science, vol. 329, no. 5990, pp. 413–417, 2010.
Busskamp V, Duebel J, Bálya D, Fradot M, Viney T, Siegert S, Groner A, Cabuy E, Forster V, Seeliger M, Biel M, Humphries P, Pâques M, Mohand Saïd S, Trono D, Deisseroth K, Sähel J, Picaud S, Roska B. 2010. Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa. Science. 329(5990), 413–417.
Busskamp, Volker, et al. “Genetic Reactivation of Cone Photoreceptors Restores Visual Responses in Retinitis Pigmentosa.” Science, vol. 329, no. 5990, American Association for the Advancement of Science, 2010, pp. 413–17, doi:10.1126/science.1190897.

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