Optogenetic therapy uses gene editing to add light-sensing molecules to cells. These cells can then be turned on and off by light. This technique has been used in research for many years to study how nerve cells work. Recently, optogenetics has also been explored as a potential therapy for vision loss. In many eye diseases, including retinitis pigmentosa (RP) and age-related macular degeneration (AMD), vision loss is caused when the cells that sense light, called photoreceptors, are damaged. Optogenetic therapy tries to create new light-sensing cells to replace lost photoreceptors.

What is Optogenetics?

The retina is a special tissue at the back of the eye where incoming light is processed. Unique, light-sensitive cells called photoreceptors absorb light and turn it into an electrical signal. This signal is passed from photoreceptors, through different layers of cells in the retina to the optic nerve. The optic nerve sends this signal to the brain where it is processed to form the image that we see.

In many types of retinal degeneration, vision loss happens when photoreceptors are damaged or lost. Without photoreceptors, we can’t sense light coming into the eye and our brain cannot receive the signals it needs to make an image. Photoreceptors can sense light because they make special proteins called opsins. Opsins change shape when exposed to light, and this kicks off an electrical signal. Opsins are normally only found in photoreceptor cells, not in other retinal cells.

In optogenetic therapy, the instructions to make an opsin protein are inserted into retinal cells that previously couldn’t sense light. When light comes into the eye, this cell is “turned on” like a photoreceptor, and start an electrical signal that is passed on to the brain.

How Does Optogenetic Therapy Work?

Gene therapy is used to deliver the opsin gene into retinal cells in the eye. After the gene therapy treatment, it can take several months for cells to make enough opsin. This means it may take some time for vision to improve. Visual rehabilitation may also be necessary to train the brain to understand and interpret the new signals.

There are many different types of opsins, and each one senses a different wavelength of light. For example, if an optogenetic therapy uses an opsin that is activated by red light, the patient might need to wear special glasses that filter out other colours so that the red light can activate the opsin. An optogenetic therapy that uses opsins that are activated by visible light might not need these special glasses.

Who is Optogenetic Therapy For?

Currently, optogenetic therapy is primarily being tested for individuals with retinitis pigmentosa who have lost most of their photoreceptors and have advanced retinal degeneration. This therapy is currently not being considered for individuals who still have many healthy photoreceptor cells and a significant amount of vision remaining.

Hopefully, in the future, optogenetic therapies could be useful for individuals with many types of retinal degeneration, including other types of inherited retinal disease such as choroideremia, Stargardt disease and rod-cone dystrophies. It may also have applications for people who are living with age-related macular degeneration.

How is Optogenetic Therapy Different from Gene Replacement Therapy?

Optogenetics uses gene therapy to add opsins to retinal cells. However, it is very different than many of the gene replacement therapies you may have heard about. In many gene therapies a new, functional copy of a gene is delivered to photoreceptor cells to replace a mutated gene that is causing photoreceptor death. Luxturna is an example of a gene replacement treatment. It is specifically for individuals with mutations in the RPE65 gene. Optogenetic therapies are not specific to only one gene and they have the potential to restore vision caused by many different gene mutations. In addition, while most gene replacement therapies work best if there are many photoreceptors remaining, optogenetic therapies have the potential to restore vision to individuals who have advanced retinal degeneration and little or no photoreceptors.

Optogenetic Therapy Clinical Trials

Early results from optogenetic clinical trials have shown some improvements in vision. The first successful test of optogenetic therapy in humans was reported in 2021 on a 58-year-old man affected by advanced retinitis pigmentosa. Seven months after the treatment, the man had partially restored vision. He could see objects such as a notebook or a staple box when using light-stimulating goggles. Since then, other people have received optogenetic treatment as part of this and other clinical trials. Optogenetics has not yet improved vision enough to allow reading or recognizing faces.

For information about optogenetic therapies that are being tested in clinical trials, visit our List of Innovative Clinical Trials page. To learn more about how clinical trials work, visit our Understanding Clinical Trials page.

To learn more, watch our View Point webinar explaining the science of optogenetics.