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Wolf Prize in Medicine 2024 for Ophthalmology Specialists for "Rehabilitation of sight in the blind through optogenetics"

the two, Jose-Alain Sahl from France, andButund Ruska From Switzerland, they promoted the field of genetic medicine for eye diseases, prevented blindness and restored sight to the blind

Prof. Jose-Alain Sahl from France, 2024 Wolff Medicine Prize winners. Photo courtesy of the Wolff Prize Foundation
Prof. Jose-Alain Sahl from France, 2024 Wolff Medicine Prize recipients. Photo courtesy of the Wolff Prize Foundation

Jose-Alain Sahl

Jose-Alain Sahl (born in 1955 - Algeria) is the chairman of the department of ophthalmology at the medical school of the University Pittsburgh, Director of the Eye Institute, UPMC and Chair of Ophthalmology at the Eye and Ear Medicine Foundation in Pittsburgh, and Professor of Ophthalmology at the Sorbonne University.

Sahl's journey is a testament to the power of passion and dedication. His parents, both educators, instilled in him humanistic principles and fostered a broad intellectual curiosity. Back in school, Sahl excelled in various subjects and showed a natural talent for mathematics and physics, and his teachers encouraged him to engage in advanced science. Alongside his passion for the sciences, he developed an affinity for poetry and philosophy. The unique fusion of interests led him to practice medicine.

Dr. Sahl studied medicine at the Denis Diderot University, Paris, VII and ophthalmology at the Louis Pasteur University in Strasbourg. He completed his medical degree with honors with a medal from the Faculty of Paris. Sahl completed a residency in ophthalmology at the Louis Pasteur University Hospital in Strasbourg. He was then a research fellow at the Massachusetts Eye and Ear Infirmary and a visiting researcher in the Department of Molecular and Cellular Biology at Harvard University. Dr. Sahl founded and managed the Eye Institute in Paris (2008-2020) and currently serves as chairman of the Department of Ophthalmology at the University of Pittsburgh School of Medicine and a professor at the Sorbonne School of Medicine.

Butund Ruska

Butund Ruska (Born in 1969 - Hungary) Researcher at the University of Basel and director of the Institute of Molecular and Clinical Ophthalmology in 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. His journey began with a musical career, he studied cello at the Franz Liszt Academy of Music (1985-1989). However, an unfortunate injury to his hand disrupted his cello career, leading him to change direction to pursue the fields of medicine and mathematics.

Roska completed his medical studies at the Smelweis University School of Medicine, Hungary, and his doctorate in neurobiology at the University of California, Berkeley. He then continued his studies in genetics and virology at Harvard Medical School. In 2005 he established a research group at the Friedrich Miescher Institute in Basel, and in 2010 he was appointed a professor at the Faculty of Medicine of the University of Basel. Today he serves as the founding director of the Institute for Molecular and Clinical Ophthalmology in Basel (IOB).

217 million people in the world suffer from moderate to severe visual impairment, and 36 million are blind. In the normal vision process when the light rays reach the retina, which is a tissue at the back of the eye, which also contains special cells that serve as light receptors (photoreceptor cells) that convert light into electrical signals. These electrical signals travel from the retina through the optic nerve to the brain, where they become the images we see. Most vision disorders can be attributed to hereditary or age-related retinal defects. Retinitis pigmentosa, a hereditary retinal disease that causes gradual deterioration of vision up to complete degeneration of the retina and blindness, can be triggered by defects in approximately 70 different genes and was considered incurable until now. It is possible that the disease can be treated at an early stage by using virus-based replacement gene therapy or by gene editing. However, this is no longer possible once the blindness has become total. And much research has been done to find a therapeutic solution.

Dr. Sahl is known for his expertise in vision rehabilitation techniques. His research focuses on diseases such as retinitis pigmentosa and age-related macular degeneration, which cause the death of the light receptor cells and lead to irreversible vision loss. Sahl and his team demonstrated the feasibility of using the chlorodopsin optogen, which is transferred via a viral vector to a nerve cell that survived in the retina, for partial vision restoration in cases of retinal degeneration in animals and humans.

At the same time, Dr. Ruska developed advanced techniques for targeted gene therapy aimed at restoring vision. His laboratory created the first detailed gene expression map of the human retina and choroid and developed methods to produce functional human retinal cells in large quantities. These cells are used to improve gene therapy approaches. As early as 2008, Roska managed to use viral vectors to inject light-sensitive proteins from green algae into the retinal cells of blind mice, thereby giving those mice their first sight. He developed a technology that allows specific cells in the eye to respond to near-infrared light using the ChrimsonR optogen Channelrhodopsin. This technique successfully reproduced light responses in the retina of blind mice.

The two scientists met in 2001 - while Ruska, who was studying for a doctorate in Berkeley, USA, came for a month to the Louis Pasteur University in Strasbourg, France, where Sahl was then the director of a laboratory. Since then, a long and fruitful collaboration began between the two - Roska, a basic science researcher and doctor of medicine, director of laboratory research in optogenetic therapies, while Sahl - a talented clinician and expert in basic and translational research - heads the development and access to patients for clinical trials. The two worked together in an attempt to reactivate the damaged retinal cells and restore their function.

In their groundbreaking study published in Medicine-Nature in May 2021, Roska and Sahl reported on the first blind patient whose vision partially returned - they demonstrated the feasibility of partial vision restoration through optogenetic therapy and engineered goggles. A retinitis pigmentosa patient whose vision was limited to primary light reception recovered and his ability to recognize, count, locate and touch different objects returned.

While optogenetics has a history of about 20 years in neuroscience, Sahl and Ruska's work marked the first demonstration of optogenetics in any human disease and a milestone in the field of treating blindness that affects millions of people worldwide.

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