Could new gene-editing technique reverse vision loss?

The potential of gene-editing technology to prevent and treat illness has attracted enormous attention over the past decade. At the heart this new wave of research is CRISPR, a tool which is being studied for a wide range of conditions, including high cholesterol, HIV and muscle diseases.

However, human studies with this experimental tool are challenging given the potential to make lasting changes to the genome. Animal studies, meanwhile, have been progressing apace.

Researchers in China have successfully restored the vision of mice with retinitis pigmentosa, one of the major causes of blindness in humans. The study, published in the Journal of Experimental Medicine, uses a new, highly versatile form of CRISPR-based genome editing with the potential to correct a wide variety of disease-causing genetic mutations.

Researchers have previously used genome editing to restore the vision of mice with genetic diseases, such as Leber congenital amaurosis, that affect the retinal pigment epithelium, a layer of non-neuronal cells in the eye that supports the light-sensing rod and cone photoreceptor cells. However, most inherited forms of blindness, including retinitis pigmentosa, are caused by genetic defects in the neural 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,’ says Prof Kai Yao at the Wuhan University of Science and Technology.

Retinitis pigmentosa can be caused by mutations in over 100 different genes and is estimated to impair the vision of 1 in 4,000 people. It begins with the dysfunction and death of dim light-sensing rod cells, before spreading to the cone cells required for colour vision, eventually leading to severe, irreversible vision loss.

Yao and colleagues attempted to rescue the vision of mice with retinitis pigmentosa caused by a mutation in the gene encoding a critical enzyme called PDE6β. To do this, the team developed a new CRISPR system which can be programmed to correct many different types of genetic mutation, regardless of where they occur within the genome.

When programmed to target the mutant PDE6β gene, the system was able to efficiently correct the mutation and restore the enzyme’s activity in the retinas of mice. This prevented the death of rod and cone photoreceptors and restored their normal electrical responses to light.

The scientists performed a variety of behavioural tests to confirm that the gene-edited mice retained their vision even into old age. For example, the animals were able to find their way out of a visually guided water maze almost as well as normal, healthy mice and showed typical head movements in response to visual stimuli.

The authors caution that much work still needs to be done to establish both the safety and efficacy of the treatment in humans. ‘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 says.