Newly developed light-sensing protein restores vision in blind mice

Review by Emily Henderson, Bachelor of ScienceOctober 22, 2020

A newly developed light-sensing protein called MCO1 opsin restores vision in blind mice when it attaches to retinal bipolar cells using gene therapy.

The National Eye Institute, which is part of the National Institute of Health, has provided SME innovation research grants to Nanoscope, LLC for the development of MCO1. The company plans clinical trials in the United States later this year.

The nanoscope findings reported today in Nature Gene Therapy indicate that completely blind mice-; imply no light perception-; regain significant retinal function and vision after treatment.

The studies described in the report showed that mice processed with standardized visual tests, such as maze navigation and motion change detection, were significantly faster.

Opsin is a protein that signals other cells as part of a cascade of signals that are essential to vision. In the normal eye, opsin is expressed by photoreceptors in the rods and cones of the retina.

When activated by light, photoreceptors emit pulses that signal other retinal neurons, the optic nerve, and neurons in the brain.

Various common eye diseases including Age-related macular degeneration Retinitis pigmentosa damages photoreceptors and impairs vision.

However, while photoreceptors may no longer be fully functional, other retinal neurons, including a class of cells called bipolar cells, remain intact. Researchers have identified ways in which bipolar cells take part in the work of damaged photoreceptors.

“The beauty of our strategy is its simplicity,” said Dr. Samarendra Mohanty, the founder of Nanoscope and the corresponding author of a report on mouse research published today in Nature Gene Therapy.

“Because bipolar cells are downstream of photoreceptors, photosensitivity is restored when the MCO1 opsin gene is added to retinal bipolar cells that have non-functional photoreceptors.”

According to researchers, this strategy can overcome the challenges plagued by other approaches to retinal regeneration. So far, gene replacement therapy has functioned primarily in rare diseases that leave photoreceptors intact, such as Leber congenital amaurosis luxulna.

Bioengineering eyes such as the Argus II retinal prosthesis require invasive surgery and wearable hardware. Other opsin replacement therapies require light enhancement to reach the threshold required for signal transduction.

However, strong light can cause further damage to the retina. Nanoscope treatment requires a single injection into the eye and does not require hardware. MCO1 is sensitive to ambient light, so you don’t need to expose it to strong light. In addition, treatment with MCO1 may treat a wider range of degenerative retinal diseases because it does not require photoreceptor survival.

Researchers have found nothing about the safety issues of treated mice. Examination of blood and tissues showed no signs of inflammation from the treatment and the treatment had no off-target effect-only bipolar cells expressed MCO1 opsin.

According to the researchers, in the best scenario, treatment may help the patient achieve 20/60 vision. However, no one knows how restored vision is compared to normal vision.

“People’s clinical studies help us understand how signal transduction through bipolar cells affects the quality of vision. For example, how well-treated eyes find fast-moving objects. Can it be done, “said Dr. Subrata Batabyal, the lead author of the manuscript. .. Treatment may be limited to the treatment of patients with severe retinal disease.

An artificial retinal approach for people with retinitis pigmentosa if this optogenetic approach, which uses cells conserved in the degenerative retina, can be proven to be effective in restoring human vision beyond the perception of light. Can provide a valuable alternative to... “

PaekGyu Lee, Ph.D., Program Officer, SME Innovation Research Program, National Eye Institute