A gene-editing experiment that restored the vision of mice might one day be used to treat a major cause of human blindness.
Scientists in China reported they used the CRISPR-based gene-editing technique to bring back vision in mice with retinitis pigmentosa.
Genome editing has previously been used to restore the vision of mice with genetic diseases such as Leber congenital amaurosis, which affect a layer of cells in the eye that supports the light-sensing rod and cone photoreceptor cells.
Most of these conditions are caused by genetic defects in the photoreceptors themselves.
“The ability to edit the genome of neural retinal cells, particularly unhealthy or dying photoreceptors, would provide much more convincing evidence for the potential applications of these genome-editing tools in treating diseases such as retinitis pigmentosa,” said researcher Kai Yao, a professor at Wuhan University of Science and Technology.
For the study, Yao's team set out to restore the vision of mice with retinitis pigmentosa caused by a flaw in a gene encoding a critical enzyme called PDE6B. For the task, they developed a more versatile CRISPR system called PESpRY. It can be programmed to correct many types of genetic mutation, no matter where they occur within the genome.
When programmed to target the mutant gene, PESpRY efficiently corrected the mutation, according to the study. It restored the enzyme’s activity in the retinas of mice.
This prevented the death of rod and cone photoreceptors and restored their normal response to light, researchers said.
Study findings were published March 17 in the Journal of Experimental Medicine.
Retinitis pigmentosa can be caused by mutations in more than 100 genes, leaving about 1 in 4,000 people with vision damage.
It starts with the failure of dim light-sensing rod cells, then spreads to the cone cells required for color vision, eventually leading to severe, irreversible vision loss.
After restoring the vision of mice, researchers conducted behavioral tests to confirm that their sight persisted even into old age. For example, the animals were able to find their way through a visually guided water maze almost as well as normal, healthy mice. They showed typical head movements in response to visual stimuli.
Yao said much work is needed to establish both the safety and efficacy of the PESpRY system in humans. Results of animal studies are often different in people.
“However, our study provides substantial evidence for the in vivo applicability of this new genome-editing strategy and its potential in diverse research and therapeutic contexts, in particular for inherited retinal diseases such as retinitis pigmentosa,” Yao said in a journal news release.
The U.S. National Institutes of Health has more on retinitis pigmentosa.
SOURCE: Journal of Experimental Medicine, news release, March 17, 2023