Gene Therapy And A Light Sensing Protein Restored Vision In Mice

The report published in Nature Gene Therapy describes basic research findings of how totally blind mice regained significant retinal function and vision after treatment; the treated mice were significantly faster in standardized visual testing such as maze navigation and detecting changes in motion. 

The light-sensing protein is called the MCO1 opsin which has been developed by Nanoscope. Opsin proteins signal other cells are part of a cascade of signals that are essential to visual perception. Typical opsins are expressed by the rod and cone photoreceptors in the retina, and when activated by the light the photoreceptors pulse and send a signal through other retinal neurons, the optic nerve, and on to neurons in the brain. 

Vision can become impaired as a result of a variety of common eye diseases, but while the photoreceptor may no longer fully function other retinal neurons including a class of bipolar cells may remain intact. The researchers have identified a way for bipolar cells to take on some of the work of damaged photoreceptors. 

“The beauty of our strategy is its simplicity,” said Samarendra Mohanty, Ph.D., Nanoscope founder and corresponding author of a report on the mouse study that appears today in Nature Gene Therapy. “Bipolar cells are downstream from the photoreceptors, so when the MCO1 opsin gene is added to bipolar cells in a retina with nonfunctioning photoreceptors, light sensitivity is restored.”

According to the team, their strategy could help to overcome challenges plagued by other approaches to retinal regeneration. Thus far gene replacement therapy has worked principally in rare diseases that leave photoreceptors intact, while bionic eye retinal prosthesis requires invasive surgery and wearable hardware. Other opsin replacement therapies require intensification of light in order to reach the threshold required for signal transduction which risks further damage to the retina. This therapy does not require any hardware and involves a one-time injection into the eye, and MCO1 is sensitive to ambient light meaning that it does not require strong light to be shined into the eye. 

MCO1 therapy may even help to treat a wider range of degenerative retinal diseases as photoreceptor survival is not required. The team did not observe any safety issues in the treated mice, and examination of blood/tissues found no signs of inflammation due to treatment, and the therapy did not display any off-target effects other than bipolar cells expressing the MCO1 opsin. 

The team suggests that under best-case scenarios this therapy could help patients to achieve 20/60 vision, but no one knows how the restored vision will compare to normal vision, and the therapy will likely be limited for the treatment of patients with severe retinal disease.

“A clinical study in people will help us understand how signaling through bipolar cells affects vision quality; for example, how well-treated eyes can pick out fast-moving objects.,” said Subrata Batabyal, Ph.D., lead author of the manuscript.  

“If this optogenetic approach using cells spared in degenerated retina can prove to be effective in vision restoration in humans, beyond light perception, it could offer a valuable alternative to the retinal prosthesis approach for people with late-stage retinitis pigmentosa,” said PaekGyu Lee, Ph.D., NEI’s program officer for the Small Business Innovation Research program.