Biography

José-Alain Sahel studied at the Faculty of Medicine, University of Paris, and completed his ophthalmology residency in Paris and Strasbourg. After a fellowship and visiting scholarship at Harvard University (Cambridge, Boston, USA), he was appointed Professor at the Louis Pasteur University in Strasbourg. He is Professor of Ophthalmology in the Faculty of Medicine at the Pierre-et-Marie-Curie University, and holds the Cumberlege Chair of Biomedical Sciences at the Institute of Ophthalmology-UniversityCollege of London. He heads an ophthalmology department at the Centre hospitalier national d'ophtalmologie (CHNO) des Quinze-Vingts and the Fondation ophtalmologique Rothschild in Paris. He founded and directs the Institut de la Vision (Pierre-et-Marie-Curie University-UPMC/Inserm/CNRS), which operates in synergy with the CHNO des Quinze-Vingts (over 250 employees).

José-Alain Sahel's fundamental and clinical research focuses on understanding the mechanisms of retinal degeneration, as well as the design, development and evaluation of innovative treatments for retinal diseases (neuroprotection, stem cells, gene therapy, pharmacology and artificial retina). José Sahel's group (with Saddek Mohand-Said and Thierry Léveillard) was the first to hypothesize and then demonstrate that a protein produced by rods enables cones to survive and thus maintain daytime, high-resolution vision. This protein, known as Rod-derived Cone Viability Factor (RdCVF), is currently the subject of translational studies with a view to administering it as a therapeutic agent to save cones and treat cone-rod dystrophies. When cones and rods have degenerated, optogenetics offers the prospect of partially restoring vision. José Sahel's group with Serge Picaud, Jens Duebel, Deniz Dalkara at the Vision Institute, Botond Roska at the Friedrich Miescher Institute for Biomedical Research in Basel, and Ernst Bamberg(Max Plack Institute, Frankfurt, Germany) have demonstrated that different retinal cell types, such as "dormant cones", can be transformed into "artificial photoreceptors" by optogenetics, enabling the reactivation of circuits and signaling pathways in the retina and the restoration of vision-related behavioral progress.

Selected bibliography

Main publications

  • Rod-derived Cone Viability Factor acts by stimulating aerobic glycolysis

    Aït-Ali N., Fridlich R., Millet-Puel G., Clérin E., Delalande F., Jaillard C., Blond F., Perrocheau L., Reichman S., Byrne L. C., Olivier-Bandini A., Bellalou J., Moyse E., Bouillaud F., Nicol X., Dalkara D., van Dorsselaer A., Sahel J.-A. et Léveillard T., « Rod-derived Cone Viability Factor acts by stimulating aerobic glycolysis », Cell, vol. 161, n° 4, 2015, p. 817-32.

  • Natural History of Geographic Atrophy Progression Secondary to Age-Related Macular Degeneration (Geographic Atrophy Progression Study)

    Schmitz-Valckenberg S., Sahel J.-A., Danis R., Fleckenstein M., Jaffe G. J., Wolf S., Pruente C. et Holz F. G., « Natural History of Geographic Atrophy Progression Secondary to Age-Related Macular Degeneration (Geographic Atrophy Progression Study) », Ophthalmology, 2015.

  • Targeting Channelrhodopsin-2 to ON-bipolar Cells With Vitreally Administered AAV Restores ON and OFF Visual Responses in Blind Mice

    Macé E., Caplette R., Marre O., Sengupta A., Chaffiol A., Barbe P. Desrosiers M., Bamberg E., Sahel J.-A., Picaud S., Duebel J. et Dalkara D., « Targeting Channelrhodopsin-2 to ON-bipolar Cells With Vitreally Administered AAV Restores ON and OFF Visual Responses in Blind Mice », Mol Ther, vol. 23, n° 1, 2015, p. 7-16.

  • Repair of rhodopsin mRNA by spliceosome-mediated RNA trans-splicing: a new approach for autosomal dominant retinitis pigmentosa

    Berger A., Lorain S., Joséphine C., Desrosiers M., Peccate C., Voit T., Garcia L., Sahel J.-A. et Bemelmans A. P., « Repair of rhodopsin mRNA by spliceosome-mediated RNA trans-splicing: a new approach for autosomal dominant retinitis pigmentosa », Mol Ther, vol. 23, n° 5, 2015, p. 918-930.

  • Viral-mediated RdCVF and RdCVFL expression protects cone and rod photoreceptors in retinal degeneration

    Byrne L. C., Dalkara D., Luna G., Fisher S. K., Clérin E., Sahel J.-A., Léveillard T. et Flannery J. G., « Viral-mediated RdCVF and RdCVFL expression protects cone and rod photoreceptors in retinal degeneration », J Clin Invest, vol. 125, n° 1, 2015, p. 105-116.

  • From confluent human iPS cells to self-forming neural retina and retinal pigmented epithelium

    Reichman S., Terray A., Slembrouck A., Nanteau C., Orieux G., Habeler W., Nandrot E. F., Sahel J.-A., Monville C. et Goureau O., « From confluent human iPS cells to self-forming neural retina and retinal pigmented epithelium », Proc Natl Acad Sci U S A, vol. 111, n° 23, 2014, p. 8518-8523.

  • Gene therapy for blindness

    Sahel J.-A. et Roska B, « Gene therapy for blindness », Ann Rev Neurosci, vol. 36, 2013, p. 467-488.

  • Nxnl2 splicing results in dual functions in neuronal cell survival and maintenance of cell integrity

    Jaillard C., Mouret A., Niepon M. L., Clérin E., Yang Y., Lee-Rivera I., Aït-Ali N., Millet-Puel G., Cronin T., Sedmak T., Raffelsberger W., Kinzel B., Trembleau A., Poch O., Bennett J., Wolfrum U., Lledo P. M., Sahel J.-A. et Léveillard T., « Nxnl2 splicing results in dual functions in neuronal cell survival and maintenance of cell integrity », Hum Mol Genet, vol. 21, n° 10, 2012, p. 2298-2311.

  • Interim results from the international trial of Second Sight's visual prosthesis

    Humayun M. S., Dorn J. D., da Cruz L., Dagnelie G., Sahel J.-A., Stanga P. E., Cideciyan A. V., Duncan J. L., Eliott D., Filley E., Ho A. C., Santos A., Safran A. B., Arditi A., Del Priore L. V., Greenberg R. J. et Argus II Study Group, « Interim results from the international trial of Second Sight's visual prosthesis », Ophthalmology, vol. 119, n° 4, 2012, p. 779-788.

  • Artificial retina: the multichannel processing of the mammalian retina achieved with a neuromorphic asynchronous light acquisition device

    Lorach H., Benosman R., Marre O., Ieng S. H., Sahel J.-A. et Picaud S., « Artificial retina: the multichannel processing of the mammalian retina achieved with a neuromorphic asynchronous light acquisition device », J Neural Eng, vol. 9, n° 6, 2012.

  • Downregulation of apoptosis-inducing factor in Harlequin mice induces progressive and severe optic atrophy which is durably prevented by AAV2-AIF1 gene therapy

    Bouaita A., Augustin S., Lechauve C., Cwerman-Thibault H., Bénit P., Simonutti M., Paques M., Rustin P., Sahel J.-A. et Corral-Debrinski M., « Downregulation of apoptosis-inducing factor in Harlequin mice induces progressive and severe optic atrophy which is durably prevented by AAV2-AIF1 gene therapy », Brain, vol. 135, part. 1, 2012, p. 35-52.

  • Poppers-associated retinal toxicity

    Vignal-Clermont C., Audo I., Sahel J.-A. et Paques M. « Poppers-associated retinal toxicity », N Engl J Med, vol. 363, n° 16, 2010, p. 1583-1585.

  • In vivo observation of the locomotion of microglial cells in the retina

    Paques M., Simonutti M., Augustin S., Goupille O., El Mathari B. et Sahel J.-A., « In vivo observation of the locomotion of microglial cells in the retina », Glia, vol. 58, n° 14, 2010, p. 1663-1668.

  • Genetic Reactivation of Cone Photoreceptors Restores Visual Responses in Retinitis pigmentosa

    Busskamp V., Duebel J., Balya D., Fradot M., Viney T. J., Siegert S., Groner A. C., Cabuy E., Forster V., Seeliger M., Biel M., Humphries P., Paques M., Mohand-Said S., Trono D., Deisseroth K., Sahel J.-A., Picaud S. et Roska B., « Genetic Reactivation of Cone Photoreceptors Restores Visual Responses in Retinitis pigmentosa », Science, vol. 329, n° 5990, 2010, p. 413-417.

  • Rod-derived cone viability factor for treating blinding diseases: from clinic to redox signaling

    Léveillard T. et Sahel J.-A., « Rod-derived cone viability factor for treating blinding diseases: from clinic to redox signaling », Sci Transl Med, vol. 2, n° 26, 2010.

  • Functional cone rescue by RdCVF protein in a dominant model of retinitis pigmentosa

    Yang Y., Mohand-Said S, Danan A., Simonutti M., Fontaine V., Clerin E., Picaud S., Léveillard T., Sahel J.-A., « Functional cone rescue by RdCVF protein in a dominant model of retinitis pigmentosa », Mol Ther, vol. 17, n° 5, 2009, p. 787-795.

  • Identification and characterization of rod-derived cone viability factor

    Léveillard T., Mohand-Saïd S., Lorentz O., Hicks D., Fintz A. C., Clérin E., Simonutti M., Forster V., Cavusoglu N., Chalmel F., Dollé P., Poch O., Lambrou G. et Sahel J.-A., « Identification and characterization of rod-derived cone viability factor », Nat Genet, vol. 36, n° 7, 2004, p. 755-759.

  • Prenatal human ocular degeneration occurs in Leber's congenital amaurosis (LCA2)

    Porto F. B., Perrault I., Hicks D., Rozet J. M., Hanoteau N., Hanein S., Kaplan J. et Sahel J.-A., « Prenatal human ocular degeneration occurs in Leber's congenital amaurosis (LCA2) », J Gene Med, vol. 4, n° 4, 2002, p. 390-396.

  • Retinitis pigmentosa: rod photoreceptor rescue by a calcium-channel blocker in the rd mouse

    Frasson M., Sahel J.-A., Fabre M., Simonutti M., Dreyfus H. et Picaud S., « Retinitis pigmentosa: rod photoreceptor rescue by a calcium-channel blocker in the rd mouse », Nat Med, vol. 5, n° 10, 1999, p. 1183-1187.

  • Normal retina releases a diffusible factor stimulating cone survival in the retinal degeneration mouse

    Mohand-Said S., Deudon-Combe A., Hicks D., Simonutti M., Forster V., Fintz A. C., Léveillard T., Dreyfus H., Sahel J.-A., « Normal retina releases a diffusible factor stimulating cone survival in the retinal degeneration mouse », Proc Natl Acad Sci U S A, vol. 95, n° 14, 1998, p. 8357-8362.