The retina of a blind mouse treated with Opto-mGluR6: The red stain shows that light antennas have been added to the retinal cells. Credit: Sonja Kleinlogel
Scientists from the University of Bern, Switzerland, and the University of Göttingen, Germany, have developed an optogenetic tool that may restore photosensitivity to retinal cells in people with hereditary blindness (PLoS Biol., doi: 10.1371/journal.pbio.1002143). In a proof-of-principle study, Bern’s Sonja Kleinlogel and her colleagues used a modified virus to insert a photosensitive protein into functional retinal cells to restore vision in mice with daylight blindness. According to the researchers, the technique overcomes limitations of previous optogenetic therapies and has the potential to restore sight to millions of people affected by progressive degenerative blindness.
The new approach from Kleinlogel and her team focuses on cells deep in the retina that usually aren’t touched by degenerative blindness. These intact cells are infected with viruses that contain genetic blueprints to turn a chemoreceptor into a photoreceptor. Cells equipped with these engineered “light antennas” can act as their own photoreceptors, thereby restoring the vision signal pathway disrupted by nonfunctional photoreceptor cells.
The light antenna is actually a chimeric protein (a protein encoded from multiple genes that have been spliced together) named Opto-mGluR6, which contains light-sensing domains from melanopsin and two local retinal proteins. The authors note the following advantages of Opto-mGluR6 over other optogenetic tools for restoring light vision:
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resistance to light bleaching means response strength doesn’t weaken with repeated use;
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local proteins make it invisible to the body and less likely to trigger an immune response;
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melanopsin domains are activated by moderate daylight as opposed to strong, potentially damaging laser light required by other optogenetic tools; and
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light signals can be naturally amplified via the undisrupted intracellular signal pathway, eliminating the need for special light goggles or intensifiers.
In addition to possibly providing a minimally invasive, clinically safe method for restoring vision, the researchers say that their proof-of-concept study of Opto-mGluR6 could inform other studies of light-activatable optogenetic tools for synaptic plasticity, memory and diseases.