Optogenetics: Hope for Vision Restoration for Advanced Retinal Diseases

Early, encouraging results from two human studies — trials launched by Bionic Sight and GenSight — are putting optogenetic therapies in the spotlight for patients with advanced vision loss (i.e., only light perception) from retinal conditions such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD).

In the Bionic Sight trial, investigators reported that the first four RP patients dosed can now see light and motion. Two of the patients can detect the direction of motion; that is, they can determine if objects are moving to the right or left. One patient said that one of the first new things he saw was Hanukkah candles on the eighth day of the holiday when they were all lit. Also, two patients who practice martial arts saw the robes of their opponents against the dark blue mat.

GenSight reported results for a 58-year-old man who entered the trial with only light perception due to advanced RP (Usher syndrome type 2A). After receiving the optogenetic therapy, the patient was able to locate and reach for objects on a table while wearing the image-capturing eyewear. Results from the GenSight trial were reported in the journal Nature Medicine. The Foundation funded lab research that led to initiation of the GenSight study.

In simple terms, optogenetic treatments bestow light sensitivity to cells that normally don’t respond to light or cells that have lost their light-sensing ability. And, they’re gene-agnostic,  designed to work independent of the mutated gene causing the patient’s retinal disease.

The emerging therapies from Bionic Sight and GenSight are designed to enable retinal ganglion cells to respond to light, so they can work like a back-up system for photoreceptors, the cells that normally make vision possible. Ganglion cells often survive after photoreceptors are lost to advanced retinal disease. In both treatments, copies of an algae-derived gene that express a light-sensing protein are delivered to the ganglion cells. Both approaches use viral gene delivery systems and include eyewear to enhance the visual information sent to the retinas.

Nanoscope Therapeutics recently launched a clinical trial in the US for its optogenetic therapy, which involves viral delivery of a light-sensitive gene (a multi-characteristic opsin) to bipolar cells in the retina. The company will enroll 27 people with advanced RP in its trial.

An emerging protein-based optogenetic approach being developed by Vedere Bio and funded by the Foundation’s RD Fund was recently acquired by Novartis. After the acquisition, Vedere Bio II was launched to develop another optogenetic therapy.

Two groups are working on optogenetic therapies designed to resurrect dormant cone photoreceptors in people with advanced retinal disease. One of the groups, SparingVision, is funded through the RD Fund. The other group is led by Hendrik Scholl, MD, Institute of Molecular and Clinical Ophthalmology Basel, and funded by the Foundation’s Translational Research Acceleration Program (TRAP).

Keep in mind that while there is much promising research activity for optogenetic therapies, the approach is still at an early stage of clinical development; there is much that the research community is learning about the potential for meaningful, natural vision restoration from optogenetics.