Scientists Use Gene Editing to Treat Retinitis Pigmentosa in Mice

Researchers funded by the National Eye Institute (NEI) have successfully used a gene-editing technique to correct a mutation responsible for retinitis pigmentosa (RP). The study, led by Krzysztof Palczewski, PhD, of the University of California, Irvine, was published on November 18 in the Proceedings of the National Academy of Sciences.

The team employed a CRISPR-Cas9-based tool called base editing to precisely target and correct a rhodopsin-150K mutation in a mouse model of RP. This mutation, which affects the rhodopsin protein critical for vision, leads to the structural and functional failure of rod photoreceptors.

In the treated mice, up to 44% of the rhodopsin gene product was successfully edited, resulting in restored rhodopsin production. Electroretinography tests revealed modest improvements in retinal function in mice treated within 15 days of birth. However, mice treated later in life, after significant retinal degeneration had occurred, showed limited improvement.

“This approach shows promise for treating inherited retinal diseases caused by rhodopsin mutations, which currently have no available treatments,” Dr. Palczewski, who collaborated with David R. Liu, PhD, of the Broad Institute of MIT and Harvard, stated in an NIH news release.

The researchers also observed that the gene-editing treatment prevented the loss of the retina's outer nuclear layer, which houses the nuclei of rod and cone photoreceptors. This preservation is critical, as rod photoreceptors support the health of cone photoreceptors, which are responsible for color vision and daytime sight.

The study suggests that further optimization of the dosing regimen and surgical technique could enhance treatment outcomes. The researchers noted that the findings pave the way for potential clinical applications, with the hope that correcting even a subset of rod photoreceptors might halt retinal degeneration and improve vision in patients.

This research was supported by NEI. For more details, the full study can be accessed at PNAS.