The thought of darkness and not being able to see sends a shiver down to the spine. If the thought is so scary then imagine the pain and difficulty for the people who suffer from the gradual loss of sight. The eye, an important organ for sight perception consists of various components and each one plays a vital role in our vision. One of the components ‘Retina’ which acts as a bridge between the light reception and interpretation of the object in the brain, consists of layers of nerve cells (photoreceptors cells) at the back of the eye which receive light from the object and generate impulses that travel through the optic nerve to the brain. Retinitis Pigmentosa (RP) is a monogenic rare hereditary disease caused in millions of people worldwide due to mutations in more than 71 different genes. It involves breakdown and loss of photoreceptor retinal cells which gradually leads to night blindness in adolescence and by middle age, the patient loses their vision completely. These mutations in the genes either lead to no production of required protein or produce a toxic form in the cell, restraining the cell function. There is no treatment for this disease yet but progression can be slowed by oral vitamin A supplements. In the absence of any specific drug for RP, a gene therapy approach has been explored. In the gene therapy approach, defective genes can be corrected either by silencing, replacing, and editing that particular gene or by introducing a new gene into the cells. Until now, there are no approved gene replacement therapies for RP except for one of the mutated gene RPE65 which is involved in the early onset of the disease.
Recently, a breakthrough study published in Nature Medicine, showed partial restoration of blindness in a late-stage RP patient by relatively and remarkably simple procedure which by further study can be used for wide applications.
RP starts with the loss of photoreceptor cells both rods and cones which are responsible for peripheral vision and central vision. It is the loss of these cells which causes blindness in these patients. Previous studies have been done to study retinal degeneration using a mouse model. In one of the studies from Dr. Botond Rosaka’s lab, an ion channel in the bipolar cells of the retina was targeted. This led to the induction of sensitivity of light in ganglion cells. Despite retinal degeneration, they restored transient responses, and signals were relayed to the brain and were sufficient for the animals to successfully perform optomotor behavioral tasks (such as locomotion assay due to light induction). A team led by Dr. José-Alain Sahel, professor of ophthalmology at Sorbonne University and the University of Pittsburgh, tried to restore the function of retinal cells in a late-stage RP patient. They used a light-sensing protein known as ChrimsonR, present in single-celled algae to sense the sunlight for movement. This protein opens the electrical channels in neurons and reactivates them to sense light. Scientists used a harmless adenovirus vector to carry the gene encoding ChrimsonR protein and then injected this virus in the fluid-filled portion of the eye behind the lens. This ChrimsonR protein stimulates electrical activity in the cells and makes them absorb the light but this process took four months.
A previous study on sensitizing the retinal cells by ChrimsonR in non-human primates has shown the expression of the protein takes about two to six months to express stably in the foveal ganglion cells and is not harmful. This elementary study acts as a groundwork for this human-based study, in which a 58-year-old male, limited to basic light vision, and has been diagnosed with RP 40 years ago. Only the poorer sites were used for the experimental purpose in case something went wrong with the experiment. Our retina is sensitive to the intensity of light, when the intensity is low it is more reactive and at high intensity its reactivity is less, to protect the damage of retinal cells. ChrimsonR protein only activates the retinal cells in the amber spectrum and is not sufficient to reinstate the exquisite interplay of rods and cones cells which give the complex and accurate colorful vision of a normal eye. The human eye can perceive only the visible spectrum of light which consists of blue, red, and green colour. Amber light arises in the orange-red spectrum. It has been known that amber emanates in warm light and is pleasant for sleeping purposes and is still enough light to see the surroundings.
To protect the patient’s eye from exposure to high-intensity light rays, special light stimulating goggles were used to convert the high light intensity to an amber spectrum range. No vision change was observed in patients with and without goggles during the visual training before virus injection. After the injection, the patient was trained for visual training such as recognizing the objects, point them, pick them and count them, over the repeated trials, there were no results but after four and half months the patient began to report signs of visual improvement. Henceforth, the patient started recognizing patterns on the street by identifying the crosswalks and also by counting the number of white stripes. The patient also improved in daily visual activities, such as detecting a mug, plate, or phone, detecting the furniture, and also the door knob-only in the presence of goggles. It was amazing that he can also detect where people are. Thus, activation of this protein along with the goggles helped in the visual recovery of the patient.
The Sahel and the team believe that this effect will last for a long time or it could be permanent also. Does this treatment is ready for application? This treatment was done only on one patient so increasing the patient number will be the next goal and also much more research is required to standardized the dosage and also for goggle improvement and including many more training methods will help the patient to have better vision. One big question will be to define the criteria and when to start the treatment in the RP patient. This study is one of the spectacular achievements and hope for late-stage RP patients.