José-Alain Sahel

José-Alain Sahel

Affiliation at the time of the award:

University of Pittsburgh School of Medicine, USA

Sorbonne Université, France

Award citation:

“for sight-saving and vision restoration to blind people using optogenetics”.

Prize share:

José-Alain Sahel

Botond Roska

Jose-Alain Sahel (born in 1955, Algeria) is the chair and Distinguished Professor of the Department of Ophthalmology at the University of Pittsburgh School of Medicine, director of the UPMC Vision Institute, and the Eye and Ear Foundation Endowed Chair of Ophthalmology and Exceptional Class Professor of Ophthalmology – Sorbonne Université.

Professor Sahel’s journey is a testament to the power of passion and dedication. He was deeply influenced by his parents, both educators, who instilled in him humanist principles and fostered a broad intellectual curiosity. Excelling across various subjects at school, Sahel displayed a natural aptitude for mathematics and physics, guided by his teachers toward the most advanced scientific pursuits. Alongside his scientific acumen, he harbored a profound appreciation for poetry and philosophy. It was this unique blend of interests that led him to choose a career in medicine.

Dr. Sahel studied medicine at the University Denis Diderot, Paris VII, and Ophthalmology at Louis Pasteur Strasbourg University. He received his medical degree with a Medal of the Faculty of Paris and obtained his specialty certification in ophthalmology. He completed a residency in Ophthalmology at the Louis Pasteur University Hospital in Strasbourg. He also was a research fellow at the Massachusetts Eye and Ear Infirmary and a visiting scholar in the Department of Molecular and Cellular Biology at Harvard University.  Dr. Sahel founded and directed the Vision Institute in Paris (2008- 2020) and is currently chair of the Department of Ophthalmology at the University of Pittsburgh School of Medicine and professor at the Sorbonne’s Medical School.

Botond Roska (born in 1969, Hungary), professor at the University of Basel and director at the Institute of Molecular and Clinical Ophthalmology Basel (IOB), is a world-renowned expert in the structure and function of retinal circuits in health and disease.

Roska is the son of a musician and a computer scientist. Initially, he pursued a musical path, learning the cello and enrolling at the Franz Liszt Academy of Music from 1985 to 1989. However, an unfortunate hand injury disrupted his cello career, leading him to redirect his focus toward medicine and mathematics.

Roska earned his M.D. degree from the Semmelweis University Medical School. He pursued a Ph.D. in neurobiology at the University of California, Berkeley, and furthered his studies in genetics and virology at Harvard University Medical School. In 2005, he established a research group at the Friedrich Miescher Institute in Basel. By 2010, Roska became a Professor at the Medical Faculty of the University of Basel. Currently, he serves as a founding director at the Institute of Molecular and Clinical Ophthalmology Basel (IOB).

The global scale of visual impairment is staggering, with 217 million people having moderate to severe vision impairment and 36 million are blind. When light hits the retina (a layer of light-sensitive cells at the back of the eye), special cells in the retina known as photoreceptors, convert the light into electrical signals. These electrical signals travel from the retina through the optic nerve to the brain, where they are transformed into the images we see. Most visual disorders can be traced back to inherited and age-dependent defects in the retina. Retinitis pigmentosa (RP) is a genetic eye disease where loss of photoreceptors can lead to complete blindness. It can be triggered by defects in approximately 70 different genes and has been considered incurable until now. It is possible that the illness can be treated at an early stage by employing virus-based gene replacement therapy or by gene editing. However, this is no longer possible once blindness has become complete. Blind people lost their eye photoreceptors making the search for a solution a complex task.

Dr. Sahel is renowned for his studies on retinal genetic and complex age-related diseases leading to photoreceptor cell death and irreversible vision loss, including retinitis pigmentosa (RP) and age-related macular degeneration (AMD). His team demonstrated the feasibility of using the photoactivatable optogene halorhodopsin delivered by a viral vector for partial vision restoration in animal and human models of retinal degeneration.

Roska developed a robust technology for cell-type targeted gene therapy and vision restoration in retinas. His laboratory generated the first single-cell transcriptome-based gene expression atlas for the human retina and choroid and then created human retinal organoids from induced pluripotent stem cells, establishing methods to generate large quantities of functional human retinal cells for optimizing gene therapy approaches ex vivo. In 2008, Roska—using gene ferries—succeeded in injecting light-sensitive channel proteins from green algae into the retinal cells of blind mice, thus giving the rodents a rudimentary form of sight.  He customized a technology to sensitize specific cell types in the eye to near-infrared light using the photoactivatable optogene channelrhodopsin ChrimsonR and demonstrated restoration of light responses in blind mice.

The two scientists met in 2001 while Roska was studying for a Ph.D. in cell and molecular biology in Berkeley, US. He had come to Strasbourg, France, to spend a month at Louis Pasteur University, where Sahel was then a laboratory director. This meeting began a long and complementary collaboration trying to reactivate photoreceptor cells in blind human retina and restore their functionality.

In a breakthrough study published in Nature Medicine in May 2021, Roska and Sahel reported the first blind patient who partially regained vision. They demonstrated the feasibility of partial vision restoration using optogenetic therapy and engineered goggles. A retinitis pigmentosa patient whose vision had been limited to rudimentary light perception regained the ability to recognize, count, locate, and touch different objects using the treated eye, following dedicated rehabilitation protocols.

While optogenetics has a nearly 20-year history in neuroscience, Sahel and Roska’s work marked the first proof-of-concept for optogenetics in any human disease and a milestone in the treatment of blinding conditions that affect millions of people worldwide.

Botond Roska and José-Alain Sahel are awarded the Wolf Prize for collectively pioneering a novel vision restoration approach by designing and applying optogenetic technology to render surviving neurons in the eye light-sensitive, functionally replacing photoreceptors lost to damage and genetic disease. This combination of powerful fundamental human neurobiological discovery research of Roska, with a deep knowledge of the clinical and translational ophthalmology of Sahel, has led to a major milestone in the fight against blindness and in the field of optogenetics more broadly.