José-Alain Sahel: His Relentless Combat to Preserve Vision

Why do some people lose their central vision? How can we preserve or restore it? These are two of the questions that have guided the career of José-Alain Sahel, and to which he has already provided many elements of response. A determination recently rewarded in Berlin with the Science Breakthrough of the Year in Life Science prize.

Photo de José-Alain Sahel
José-Alain Sahel © François Guénet/Inserm

Ophthalmology is a complete discipline – it is medical, surgical, technological, aesthetic and human, all at the same time. This multitude of facets won me over just a few months into my internship with Dr. Jean Ganem at Rothschild Ophthalmological Foundation in Paris – one I went into somewhat by chance after my medical doctorate,” recalls Professor José-Alain Sahel*, director of the Parisian university hospital institute (IHU) FOReSIGHT. The result being that he who was originally destined for pediatric oncology in the end embarked on an ophthalmology residency, which he completed in 1984 at University Hospitals Strasbourg. He then became chief resident, whilst embarking on the study of neuroscience – the retina being part of the central nervous system. “However, my aim was not to stay in a hospital setting, where the strict hierarchy did not suit me. Back then, I hoped to set up my own practice in the community,” notes the researcher.

But that was without counting on the patients… and their legitimate impatience. “The patient is supposed to represent the question, and the doctor the answer. But the doctor does not always have the answers! Sometimes he or she has to seek them in unlikely places, and then play the role of intermediary between research and clinical care.” During a post-doctoral fellowship at Harvard University in the US, Sahel realized that this intermediate state was indeed possible: he would become both a clinician and a researcher. A path that he had to forge in what he calls “a form of illegitimacy.” I did not take the royal research route: dissertation, prestigious research institute, dual medical curriculum. But I continued my merry way anyway because I saw no other way of doing what I wanted to do. Which was to fill gaping holes in ophthalmological research. “On the one hand, it was a high-performing and most rewarding specialty: you could perform surgery and see the benefits in the patient the very next day, emphasizes the scientist. On the other hand, there were whole swathes of illnesses for which there was nothing we could do, especially those related to aging and genetics. ”

Addressing major challenges

Appointed professor at University Hospitals Strasbourg at just 32 years of age, Sahel saw in it the opportunity to settle in and play the long game of addressing these major challenges. He began his research alone, following which his team gradually grew to form a small Inserm unit. He then decided to devote himself to retinitis pigmentosa, a group of degenerative hereditary diseases of the retina that primarily affect the photoreceptor cells – the rods and cones. Back then, the genes involved had not yet been identified and blindness was inevitable. But the researcher refused to accept that. Where does the loss of central vision come from? Thanks to his teams and to an invaluable collaboration with molecular biologist Thierry Léveillard*, he gradually acquired some elements of response.

Nearly 30 years later, the mechanism involved has been identified, the treatment proven to work in animals, and the start-up Sparing Vision, which will drive clinical research in 2022, has been created. “It was long, difficult, and several times we almost gave up, recalls Sahel. In research, we always go through intense moments of discouragement. The important thing is that they make you grow. And if I have one characteristic that prevails over the others, it is tenacity. ”

It is this same tenacity that also allowed him to give life to one of the most important integrated research centers dedicated to vision diseases. In 2001, he left Strasbourg to join Quinze-Vingts Hospital in Paris and embarked on a project to found the Vision Institute*. It was completed in 2008 but destroyed in a fire one month later. “We had to go a year and a half without premises, without a lab, recalls the professor. Looking back, I do not know how we did it. The resilience of the teams was impressive. 

From around one hundred researchers in 2009, the Vision Institute hosts three times as many today. Its watchwords? Multidisciplinarity and curiosity. “The most wonderful thing throughout my career has been working as a team, insists Sahel. At the Institute, we have doctors, researchers, and industry players, working together, centered around patients. It is the open questions that everyone asks themselves that create fruitful links. Questions fueled by both the patients’ pressing expectation of concrete answers and by our own curiosity. ”

Award-winning successes

It is a formula that works: research is progressing in leaps and bounds and has already led to the creation of a dozen start-ups intended to bring the Institute’s medical innovations to market. For example, Pixium Vision, the extension of another of Sahel’s great adventures: that of the artificial retina. Started in 1996 with Inserm researcher Serge Picaud and Professor Avinoam Safran, head of the Department of Ophthalmology at University Hospitals Geneva, in Switzerland, it led to the first artificial retina being implanted in 2008. Today two international clinical trials are underway, in partnership with Stanford University in the US, with the aim of restoring sight to those who have lost it through age-related macular degeneration.

Also on the Vision Institute’s list of successes are advances in gene therapy for genetic diseases of the retina and optic neuropathy. Or the first optogenetic treatment, which has enabled two patients with retinitis pigmentosa to once again be able to locate, touch and count objects. “The best moments in a researcher’s life are those of discovery – of which we have been fortunate to experience several,” acknowledges Sahel. In 2021, the internationally recognized Science Breakthrough of the Year in Life Science prize, awarded to him by the Falling Walls Foundation in Berlin, thus highlights a life of research dedicated to fighting blindness.

After 12 years at the helm of the Vision Institute, Sahel left his place to his collaborator, Picaud, on January 1, 2021. But he remains director of IHU FOReSIGHT, which he founded in 2019. This brings together Inserm, Sorbonne University and Quinze-Vingts Hospital in Paris around the Vision Institute and aims to facilitate research into vision loss by combining scientific expertise and treatment centers. Sahel is also now Director of the Department of Ophthalmology at the University of Pittsburgh, in the US, where he is supervising the creation of a US Vision Institute, which is already working in close conjunction with its Paris counterpart. His mind continues to brim with research projects and ideas, from optic nerve regeneration to brain stimulation for people with blindness, not to mention the social dimension of health and research, in collaboration with philosophers, in the experience of patients. Always fueled by the same desire: to shed light, and to help.

*Unit 968 Inserm/CNRS/Sorbonne Université, Vision Institute, Paris