Every so often, you see flashes of light and flickers of shadows. You might notice your poor vision in the dark. Even dimly lit rooms start to fade and blur. Over time, your peripheral vision worsens, a black void gnawing at the corners of your sight. 

Concerned, you visit an optometrist and receive your diagnosis. Retinitis pigmentosa. 

You now know that eventually, all you will see is a small spot of light at the center of your vision—not even large enough to see the faces of your loved ones. You might go completely blind. To make matters worse, your optometrist tells you that it’s hereditary—an autosomal dominant disorder caused by a single rhodopsin gene mutation. How will you tell your children that they, too, could inherit this dreadful fate? 

For decades, no treatment existed to mitigate retinitis pigmentosa for you and your children. But now, that might be about to change. 

The research of biologists Botond Roska and José-Alain Sahel focuses on using gene therapy to target degenerating photoreceptors in the eyes. Simply put, retinitis pigmentosa (RP) leads to the progressive degeneration of rod and cone photoreceptors in the retina. Rod cells, which are necessary for low-light vision, die off first, resulting in the initial night blindness that many experience with RP. Afterwards, cone cells, which are necessary for color and daytime vision, will gradually degenerate.

To restore vision for patients with RP, Roska and Sahel use optogenetics—a gene therapy approach to inject light-sensitive proteins into the retina. For patients in the early stages of retinitis pigmentosa, where some of their rod and cone cells are still intact (only nonfunctional), optogenetics can target them directly. Using safe, modified adeno-associated viruses (AAVs) to transfer beneficial genetic material into cells, researchers can introduce the genes for light-sensitive proteins. Once inside the cells, these genes express the proteins that enable otherwise light-insensitive cells to respond to light. 

The reality of this optogenetic treatment is much more complicated. Specifically, Roska and Sahel’s optogenetic approach uses two light-sensitive proteins that respond to different wavelengths of light. One protein excites the retinal cells, and the other inhibits activity. Together, these proteins mimic the biological visual process, creating contrast in vision. More recently, Roska and Sahel focused on a particular light-sensitive protein, ChrimsonR. By fusing that protein with a red fluorescent protein, the scientists can allow the proteins to respond to longer wavelengths of light, which causes less pupil construction and can be safer for patients.

Further complications arise for patients in later stages of RP, as very few rod and cone cells are intact. In some cases, researchers need to target bipolar and amacrine cells instead, which function to process information from rod and cone cells and transfer them to ganglion cells that send nerve signals to the brain. To treat RP, these bipolar and amacrine cells must be transformed into light-sensitive cells. In advanced stages of RP, even bipolar cells may be depleted. In these scenarios, ganglion cells are directly transformed and targeted for treatment.

To further complicate this treatment, all RP patients may wear special goggles. Since optogenetics has a narrower range of light sensitivity than natural photoreceptors, goggles help adjust light intensity and range to suit modified cells. The latest developments with this treatment use light-activated versions of these goggles to directly pulse light into patients’ eyes that stimulate the ChrimsonR proteins. Although this technique results in a lack of color perception, a breakthrough in 2021 allowed a 58-year-old patient with late-stage RP to gain partial visual recovery.

Optogenetics brings new hope for people living with retinitis pigmentosa. Although the absence of color perception remains a significant challenge, researchers are continually theorizing methods to overcome such barriers. One such approach is the introduction of a wide range of optogenetic sensors for different wavelengths. 

The future of RP treatment is bright. For once, that dark void may recede from the corners of your eyes, its hold upon your vision lifted. One day, even dimly lit rooms are filled with rich details. You turn to look at your family and see their faces, gleaming with joy. Finally, you realize that you can offer hope to your children.