Cross section of degenerated retina
Sight Restored to Mice Afflicted With Retinitis Pigmentosa
07 July 2010
Swiss researchers from the Friedrich Miescher Institute, in collaboration other, have restored sight to mice afflicted with retinitis pigmentosa. The results have been confirmed ex-vivo, on human tissue cultures. The team, led by Jose-Alain Sahel, is also reported as having determined the types of patient who could benefit from the therapy.
Retinitis pigmentosa is manifested by a progressive loss of sight, eventually leading to blindness. It is a form of inherited retinal degeneration that affects the light-sensitive cells of the retina : photoreceptors. Photoreceptors convert light into nerve impulses which are then transmitted to the brain. There are two types of photoreceptors: rods and cones.
The disease leads initially to degeneration of the rods which are responsible for night vision, and then the cones, which are responsible for diurnal vision, become affected. Whereas the rods are destroyed, the cones survive in the organism for extended periods, even after blindness. This inspired the researchers to develop a genetic therapy to restore the visual function of the cones which were defective (dormant) but remained present.
At the stage of the disease where the researchers have intervened, the cones still retain some electrical properties and their connections. Hence, they are able to be activated artificially. Earlier work had shown that light-sensitive ionic channels had the ability to modulate electrical activity from various neurons into which they had been introduced, in response to the level of light.
By combining these two observations, the researchers have succeeded in reactivating cones and thus allowing re-stimulation of the mice's transmission channels. To achieve this, they have introduced a protein, via a genetic therapy vector, which is capable of coupling luminous stimulation to ionic transport, hence reintroducing the phototransduction cascade required for vision. The researchers have therefore recreated a genuine biological photoelectric system.
These results are very promising, as they have been confirmed by Serge Picaud and researchers at the Institut de la Vision using human retina in cultures and therapeutic vectors for which human compatibility has already been demonstrated. The photosensitive protein can be expressed in human cone photoreceptors to which it confers a new sensitivity to light.
"We integrated the clinical approach as soon as we obtained the first fundamental results of this work. So, at the national reference centre for rare diseases of the retina, thanks to non-invasive high-resolution retinal imaging techniques, we can now target patients to whom this therapy could be applied" explains José Alain Sahel, who also points out that the transition from mice to man always carries many uncertainties. “
Professor John Marshall, Chair of the RP Fighting Blindness (British Retinitis Pigmentosa Society) Medical Advisory Board, commented “This is something that (has been speculated) about for years and I'm absolutely delighted that someone has at last investigated the potential. Useful clinical treatment is a long way off but this is a step in the right direction, activating cells that are already present and therefore do not require all the complex wiring that implants or stem cells would demand. I think this is great news but, it should be emphasised, it is very basic research at this stage. The real breakthrough is when we can actually get the dormant cones to regenerate new outer segments.”
David Head, Chief Executive, added “This approach was recently highlighted at the Retina International Congress in Italy and seems really exciting. Of course, as ever, we have to remain realistic about the time scales to progress this type of work but several research groups are working on similar approaches and we look forward to further progress and results.”
The full story is linked below. Note that this project is not funded by RP Fighting Blindness.
Retinitis pigmentosa is manifested by a progressive loss of sight, eventually leading to blindness. It is a form of inherited retinal degeneration that affects the light-sensitive cells of the retina : photoreceptors. Photoreceptors convert light into nerve impulses which are then transmitted to the brain. There are two types of photoreceptors: rods and cones.
The disease leads initially to degeneration of the rods which are responsible for night vision, and then the cones, which are responsible for diurnal vision, become affected. Whereas the rods are destroyed, the cones survive in the organism for extended periods, even after blindness. This inspired the researchers to develop a genetic therapy to restore the visual function of the cones which were defective (dormant) but remained present.
At the stage of the disease where the researchers have intervened, the cones still retain some electrical properties and their connections. Hence, they are able to be activated artificially. Earlier work had shown that light-sensitive ionic channels had the ability to modulate electrical activity from various neurons into which they had been introduced, in response to the level of light.
By combining these two observations, the researchers have succeeded in reactivating cones and thus allowing re-stimulation of the mice's transmission channels. To achieve this, they have introduced a protein, via a genetic therapy vector, which is capable of coupling luminous stimulation to ionic transport, hence reintroducing the phototransduction cascade required for vision. The researchers have therefore recreated a genuine biological photoelectric system.
These results are very promising, as they have been confirmed by Serge Picaud and researchers at the Institut de la Vision using human retina in cultures and therapeutic vectors for which human compatibility has already been demonstrated. The photosensitive protein can be expressed in human cone photoreceptors to which it confers a new sensitivity to light.
"We integrated the clinical approach as soon as we obtained the first fundamental results of this work. So, at the national reference centre for rare diseases of the retina, thanks to non-invasive high-resolution retinal imaging techniques, we can now target patients to whom this therapy could be applied" explains José Alain Sahel, who also points out that the transition from mice to man always carries many uncertainties. “
Professor John Marshall, Chair of the RP Fighting Blindness (British Retinitis Pigmentosa Society) Medical Advisory Board, commented “This is something that (has been speculated) about for years and I'm absolutely delighted that someone has at last investigated the potential. Useful clinical treatment is a long way off but this is a step in the right direction, activating cells that are already present and therefore do not require all the complex wiring that implants or stem cells would demand. I think this is great news but, it should be emphasised, it is very basic research at this stage. The real breakthrough is when we can actually get the dormant cones to regenerate new outer segments.”
David Head, Chief Executive, added “This approach was recently highlighted at the Retina International Congress in Italy and seems really exciting. Of course, as ever, we have to remain realistic about the time scales to progress this type of work but several research groups are working on similar approaches and we look forward to further progress and results.”
The full story is linked below. Note that this project is not funded by RP Fighting Blindness.
