Is optogenetics the cure to retinitis pigmentosa?

Can genetic engineering be used to cure blindness? How is genetics important in vision? Find the answers in this review of: Partial recovery of visual function in a blind patient after optogenetic therapy. Sahel JA, Boulanger-Scemama E, Pagot C, Arleo A, Galluppi F, Martel JN, Esposti SD, Delaux A, de Saint Aubert JB, de Montleau C, Gutman E, Audo I, Duebel J, Picaud S, Dalkara D, Blouin L, Taiel M, Roska B. Nat Med. 2021 Jul;27(7):1223-1229. doi: 10.1038/s41591-021-01351-4.
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Come along with us as we meet Mike, a patient diagnosed with retinitis pigmentosa and discover the revolutionary treatment he received that partially restored his vision.
Retinitis pigmentosa is an inherited disease that causes damage to the retina. In Mike’s case it limited his vision to just light perception, meaning he could only see shades of light and dark. In healthy retinas, the photoreceptors are responsible for converting light into electrical signals through a series of cells that act as a pathway to the brain. The first cells in this pathway are the photoreceptors, cells covered in rhodopsins, protein channels that open to allow sodium ions into the cell when light hits them. The problem with Mike’s eyes is that the photoreceptors are not working properly and not sending electrical signals to his brain, causing his loss of vision. The solution to this was to convert the retinal ganglion cells, a cell further up the signal pathway, into a makeshift photoreceptor, bypassing any damage before it. This was done through optogenetics, a technique that involves transferring genes that produce proteins then controlling the proteins through light.
Genes that encode for a rhodopsin called ChrimsonR were delivered to the retinal ganglion cells through adeno-associated viral vectors injected into the eye. These viral vectors are genetically engineered viruses that can carry and deliver a gene into a host cell genome. After the cells were infected, they could produce ChrimsonR on the cell membrane and respond to amber light.
Mike was then given special goggles that used a camera to convert his surroundings into amber light that was projected onto his eye. In the tests conducted, Mike was able to reach and touch a notebook on a table almost every time, whilst without the goggles, he could not.
This result on Mike wouldn’t be possible without previous studies. Specifically, experiments were conducted on the crab-eating macaque, a nonhuman primate, to ensure that it was safe for Mike. What researchers determined in these experiments was an appropriate dosage that would not cause a significant immune response and that the viral vector was more effective when both ChrimsonR and another protein, tdTomato, was expressed together rather than ChrimsonR alone. With success in this experiment on Mike, we see that optogenetics is a powerful tool that has the potential to cure other inherited diseases of the retina and more so come along and find out more.
Creator: Derrick Chong
References:
Sahel, J.A., E. Boulanger-Scemama, C. Pagot, A. Arleo, F. Gallupi et al., 2021 Partial recovery of visual function in a blind patient after optogenetic therapy. Nat. Med. 27: 1223-1229
McLaughlin, S.K., P. Collis, P.L. Hermonat, N. Muzyczka, 1988 Adeno-associated virus general transduction vectors: analysis of proviral structures. J. Virol. 62: 1963-1973
Gauvain, G., H. Akolkar, A. Chaffiole, F. Arcizet, M.A. Khoei et al. 2021 Optogenetic therapy: high spatiotemporal resolution and pattern discrimination compatible with vision restoration in non-human primates. Commun. Biol. 4: 125-125
Klapper. S.D., A. Swiersy, E. Bamberg, V. Busskamp, 2016 Biophysical properties of optogenetic tools and their application for vision restoration approaches. Front. Syst. Neurosci. 10: 74-74
Busskamp. V., J. Duebel, D. Balya, M. Fradot, T.J. Viney et al. 2010 Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa. Science. 329: 413-417