Scientists restore vision in retinitis pigmentosa using an archaebacterial protein. Introducing halorhodopsin into the remaining but nonfunctional cone photoreceptors of the retina of mice not only reactivates the cone cells’ ability to interact with the rest of the visual system, it also prompts sophisticating visually guided behavior. The scientists were able to validate their results in lightinsensitive human retinas in vitro, which were able to respond to light again after
The retina is the light sensitive tissue lining the inner surface of the eye. It is a complex, layered structure with several layers of neurons interconnected by synapses. The only neurons sensitive to light are the photoreceptors. These are grouped into two types: the cones and the rods. The signals from the rods and cones undergo complex processing by other neurons in the retina and are sent to the visual centers of the brain through the optic nerve. If the photoreceptors don’t work anymore, the human becomes blind.
Retinitis pigmentosa is a diverse group of hereditary diseases that lead to incurable blindness and affect two million people worldwide. Despite the diversity of its cause, the manifestation of the disease is similar: the highly sensitive rod photoreceptors, which allow us to see in the dusk, die. Intriguingly, the cones that operate during daylight and are responsible for highresolution color vision survive longer, though they gradually lose their function. However, it was unknown if these persisting photoreceptors would be accessible for therapeutic intervention.
Neurobiologists now have devised a gene therapeutic method to restore the functionality of the cone cells in models of retinitis pigmentosa. In a groundbreaking approach they used a light-sensitive protein called halorhodopsin from archaebacteria to re-establish vision. They were not only able to specifically produce halorhodopsin in the dormant cone cells of mice with retinitis pigmentosa, but they could also show that the cones were able to interact with the rest of the visual system. The existing network of cells was able to reproduce many of the functions of the complicated cascade of molecular events that turn a unit of light into a neuronal signal. What is more, behavioral tests indicated that the retinal information was used for visually guided behavior. The remaining cone cells are therefore an optimal target for gene-therapeutic intervention in disease where photoreceptor function is lost.
As a first step to translate these findings to patients, the research group introduced the archaebacterial halorhodopsin into nonfunctional human cone cells. And these treated cones in isolated human retinas started to respond to light.
“We believe that with our gene therapeutic method we have found a powerful approach that could eventually help a subset of retinitis pigmentosa patients,” comments the responsable researcher Botond Roska.
Busskamp V, Duebel J, Balya D, Fradot M, Viney JT, Siegert S, Groner AC, Cabuy E, Forster V, Seeliger M, Biel M, Humphries P, Paques M, Mohand-Said S, Trono D, Deisseroth K, Sahel JA, Picaud S, Roska B. (2010): Genetic Reactivation of ConePhotoreceptors Restores Visual Responses in Retinitis Pigmentosa.