Earlier this year, the first human trials of optogenetics were launched by RetroSense Therapeutics, a Michigan-based biotechnology company seeking to restore sight to patients with retinal degenerative conditions through the use of innovative gene therapy techniques. Read on to learn more about what optogenetics could mean for the future of vision restoration.
What is optogenetics?
Developed in neuroscience labs a decade ago, optogenetics is a technology that precisely controls nerves by genetically modifying neurons in order to make them responsive to light. By controlling incoming light, scientists are able to control the neurons.
How is optogenetics being used in the RetroSense clinical trial?
The RetroSense clinical trial is using photoreceptive algae to attempt to partially restore sight to patients who have been affected by retinitis pigmentosa. The condition affects the eye’s vital photoreceptor cells, which help us see by converting light into electrical signals that the brain can interpret. The condition causes these cells to gradually degenerate over time; people with retinitis pigmentosa lose peripheral and night vision first, and can eventually go completely blind.
The optogenetics technique used in the RetroSense study intends to compensate for these broken photoreceptor cells by making ganglion cells light-sensitive. Ganglions are a type of nerve cell located in the eye that transfers signals to the brain from the retina. Doctors in the study will inject DNA from a species of photoreceptive algae into the eyes of 15 trial patients; the DNA will instruct patients’ ganglion cells to start producing channelrhodopsin, the same light-responsive protein that the algae uses to detect light. When the ganglion cells have produced this protein, they should fire, or send signals to the brain, when they are exposed to light, which is exactly what the photoreceptors in a healthy retina do under normal circumstances.
Will the techniques used in the RetroSense trial be able to completely restore sight?
At present, the goal of the RetroSense study is simply to restore some vision to an eye that currently has no ability to perceive light. Trial patients are by no means expected to regain 20/20, full-color vision through optogenetics, but rather to demonstrate more modest improvements, like being able to see enough to cross a road safely or perceive when someone else is in a room with them. Though these advances might seem small, they can make a big difference in the lives of retinitis pigmentosa patients, especially given that there are almost no treatments currently available for people with this condition.
What are some challenges the RetroSense study may encounter?
The optogenetics technique that RetroSense is testing in its clinical trials is promising, but not without limitations. For example, the algae protein is less sensitive to light than a healthy retina is, so trial patients might see adequately in outdoor light but not indoors, as indoor light can be about 10,000 times dimmer than an outdoor environment.
In addition, because of this lessened sensitivity, the light-sensing ganglion cells created by the optogenetics therapy might not be able to adapt or adjust as effectively to changes in light, like the changes that occur when moving from inside to outside. The RetroSense therapy might therefore need to be further combined with other aids, like video-projection glasses, which can better adjust incoming light to the modified eye.
Another potential challenge arises from the fact that the algae protein is only responsive to the blue component of natural light. This could mean that patients who undergo the therapy might only be able to experience monochromatic vision, or perceive any object that doesn’t reflect blue light as if it were black.
Is optogenetics just for use in the eye?
Optogenetics was originally developed by neuroscientists as a tool for better understanding the brain. During its decade-long history, the study of optogenetics in animals has helped researchers greatly increase our knowledge about the brain cells that underlie movement, motivation, pain, and other basic brain functions. For example, under the guidance of Karl Deisseroth (one of the inventors of optogenetics), a team of researchers at Stanford University discovered that, by directing light through a fiber-optic cable at specific brain cells in mice, they were able to turn the sensation of fear on and off.
Recently, the eye has become a prime target for optogenetics testing because it is in many ways the easiest place to use this therapeutic technique in humans. The eye is transparent, light-sensitive, and easily accessible, and because light shines directly onto the retina, there’s no need for extra hardware or fiber-optic cables.
In addition to the RetroSense trial, a number of other optogenetics treatments are currently in development, including an optogenetic treatment for chronic pain, and a technique for controlling the tremors of Parkinson’s disease by using a light source inside the brain.