José-Alain Sahel, MD, is a clinician-scientist conducting research on vision restoration focusing on cellular and molecular mechanisms underlying retinal degeneration, and development of treatments for currently untreatable retinal diseases. He is the Endowed Distinguished Professor and Chairman of the Department of Ophthalmology at the University of Pittsburgh School of Medicine/UPMC. He founded and led the Vision Institute (Sorbonne Université-Inserm-CNRS) in Paris, France, one of the world’s largest interdisciplinary research centers focused on vision and its disorders. His work has contributed to understanding and preventing vision loss from photoreceptor cell degeneration in retinal degeneration. He developed gene-independent therapeutic strategies and led several clinical trials on retinal conditions, including first-in-human trials of artificial retina, gene therapy, neuroprotection, and optogenetics. The trial in optogenetics, representing the culmination of many works of preclinical research provided the first-ever clinical demonstration of the benefit of optogenetics in functional restoration. Another significant discovery is the validation of his hypothesis that loss of central and light-adapted peripheral vision in retinal degenerations results from the loss of expression of a trophic factor, which his team identified, as well as the underlying mechanism of action, leading to a novel therapeutic approach potentially applicable to all affected patients, now in clinical trials internationally. He has authored more than 90 patents and 700 peer-reviewed publications, many of these in leading journals. Among multiple grants from the European Union, the National Agency for Research, the Department of Defense, and the National Institute of Health, he coordinated the Institut Hospitalo-Universitaire FOReSIGHT and the European Research Council Synergy Grant HELMHOLTZ, developing breakthrough imaging technologies. He has co-founded companies developing innovative therapies for vision restoration and received multiple awards, including the 2024 Wolf Prize in Medicine (with Botond Roska), and is an Honoris Causa Doctorate of the University of Geneva. He is a member of several academies including the Académie des Sciences-Institut de France, the Académie des Technologies, the German National Academy of Sciences Leopoldina, and is a fellow of the National Academy of Inventors.
Research Focus
The primary focus of Dr. Sahel's laboratory and clinical investigations is to understand the mechanisms associated with retinal degeneration to develop vision restoration therapies. Together with his collaborators, he has been working on: i) understanding the pathobiology of retinal conditions to further the conception, development, and evaluation of innovative treatments for retinal diseases, with a particular focus on genetic rod-cone dystrophies and age-related retinal degenerations; ii) translation to the clinic of sight-saving approaches, including neuroprotection, stem cells, gene therapy and optogenetics, pharmacology, and visual prostheses.
- Together with his team, he worked on the conception, development, and evaluation of innovative treatments for retinal diseases -with a special focus on genetic rod-cone dystrophies- including neuroprotection, stem cells, gene therapy, pharmacology, and artificial retina. He was the first to hypothesize and demonstrate that rod photoreceptors produce a protein that rescues cone photoreceptors, thereby maintaining light-adapted and high-resolution vision. Dr. Sahel (with S. Mohand-Said and Thierry Leveillard) identified the underlying signal: Rod-derived Cone Viability Factor (RdCVF) and determined its mechanisms of action (stimulation of aerobic glycolysis, and antioxidant).
- RdCVF use is now in translation as a possible therapeutic agent to save cones and treat a spectrum of retinal degenerative diseases as a mutation independent strategy.
- Utilizing a variety of molecular and functional genomics approaches, his group aims to identify novel disease-causing genes for retinal degenerations. Besides research on developmental biology, functional genomics, physiology and therapeutics, his team (with M.Paques, S. Mohand-Said and I. Audo) conducts research on genotype-phenotype correlations with high resolution in vivo non-invasive high-resolution retinal imaging techniques (optical coherence tomography and adaptive optics) aiming at identifying patients eligible for clinical application of innovative therapies. Together with M. Fink (Institut Langevin), he led a very competitive, large, ERC-Synergy grant (2014-2021) aiming at developing novel technologies for morpho-functional imaging of the visual system.
- They have developed a number of regenerative therapeutic approaches to restore vision such as gene therapy (including the first advanced trials on mitochondrial diseases), leading to the first demonstration in several large-scale randomized trials of the efficacy of Gene Therapy in Leber Hereditary Optic Neuropathy.
- With Botond Roska at the Institute of Ophthalmology of Basel, Serge Picaud, and Deniz Dalkara at Institut de la Vision in Paris, he demonstrated that different retinal cell types such as "dormant cones" and Ganglion Cells can be converted into “artificial photoreceptors” by targeting the expression of genetically encoded light sensors enabling mice with retinal degeneration to perform visually guided behaviors. He led the first demonstration of the efficacy of Optogenetics in partial function restoration in humans. He also led (with Dr. Palanker) the first in-human wireless artificial retina trial. These programs are continuing with several funded projects, in collaboration with Leah Byrne, Morgan DiLeo, Joseph Martel, Isabelle Audo, Marle Behrmann, Deniz Dalkara, Serge Picaud, Valentina Emiliani, Daniel Palanker, and Botond Roska for the development of high-resolution stimulation methods.