With the help of optogenetic therapy, researchers have partially restored the eyesight of a blind man. The 58-year-old had gradually lost his eyesight 40 years ago due to the hereditary disease retinitis pigmentosa. For the experimental therapy, the researchers made certain cells in his eye sensitive to light with the help of injected genes. In addition, they developed special glasses that cast light at the right wavelength onto the retina. After several months of training, the man was able to recognize shapes and identify objects. The case study shows the potential of optogenetics and gives hope for future therapies.
Those who suffer from the genetic disease retinitis pigmentosa gradually lose sight. The cause are various mutations that ensure that the light-sensitive cells of the retina are destroyed. Around 40,000 people in Germany are affected by the neurodegenerative disease. There are various research approaches to treatment – including stem cell therapies and implantable retinal chips. So far, a gene therapy that can help patients with a certain mutation in the early stages of the disease has been approved. However, since the disease can be caused by various mutations, therapy has so far been lacking for the majority of patients.
Gene therapy makes cells sensitive to light
A team led by José-Alain Sahel from the Sorbonne Université in Paris has now tested a treatment approach that promises improvement regardless of the type of underlying mutation. To do this, the researchers used optogenetic methods. With the help of a viral vector, genetic material is smuggled into cells, which makes them light-sensitive. The virus serves as a gene ferry to bring the new genetic material to the desired location. The technology has been used in research for around 20 years to trigger reactions in cells with light pulses. Sahel and his colleagues have now explored the therapeutic potential of optogenetics.
For their feasibility study, they injected a 58-year-old man who was diagnosed with retinitis pigmentosa 40 years ago with viral vectors that carried the genetic material for a light-sensitive protein called ChrimsonR. This so-called channel rhodopsin forms ion channels in the cell membrane. If it is stimulated by light, the channels open and ensure that signals are passed on to the downstream cells in the brain. In this way, Sahel’s team made the glial cells in the blind person’s eye sensitive to light – cells that would otherwise not pick up any optical signals.
Seeing with special glasses
After four and a half months, when ChrimsonR production in the cells had stabilized, the researchers began eye training with the test person. Since ChrimsonR only reacts to yellow-orange light and this has to have a higher intensity than occurs in normal brightness conditions, the researchers developed special glasses in which a camera records the surroundings, the image in real time in yellow-orange light of the right type Strength converts and throws on the retina. And indeed: after seven months of training, the test subject was able to use the glasses to identify, count and specifically touch objects in the laboratory and in everyday life.
As hoped, the EEG showed that the visual center in the brain was activated, while the test subject with his special glasses watched as the researchers placed a cup on a table and removed it again. There were no side effects during the study. “The study results prove the concept that optogenetic gene therapy for partial restoration of vision is feasible,” says co-author Botond Roska from the University of Basel. However, the test person cannot recognize more than rough shapes and for this, too, he first had to learn to visually scan his surroundings with head movements. Because only a small part of the cells in his eye became sensitive to light as a result of the therapy, his field of vision is very limited.
(Video: IOB Basel)
Not yet ready for use
“An expression of photoreceptors in secondary cells of the retina will never be able to restore full vision. However, the fact that an optogenetically treated patient can visually orientate himself in his environment and count the crosswalks on the street is certainly a great success and a gain in quality of life, “comments neuroscientist Peter Hegemann from the Humboldt University in Berlin was not involved in the study. Clinical use is not yet foreseeable. First of all, the technology must be tested and improved in further studies. For example, it is desirable that the light-sensitive proteins are more evenly distributed over the retina and that they respond better to natural light. In the current experiment, the patient was dependent on the special glasses.
The authors of the study also emphasize that a lot of research is needed before the therapy can be offered to patients. In the next step, they want to test the procedure with other test subjects and develop it further.
Source: José-Alain Sahel (Sorbonne Université, Paris) et al., Nature Medicine, doi: 10.1038 / s41591-021-01351-4