Researchers at the University of California San Diego (UCSD) School of Medicine and the Shiley Eye Institute have collaborated with researchers in China to discover a way to reverse the effects of retinitis pigmentosa (RP) in mice.
RP is a chronic inherited genetic eye disorder caused by mutations in more than 60 genes that eventually lead to permanent blindness. It affects about one in every 4,000 people worldwide and about 100,000 people in America.
Within eyes there are two different types of photoreceptors: rods and cones. Rods are responsible for scotopic vision, or vision in the dark. They also handle peripheral vision and as a result, they do produce dull images. Cones, on the other hand, are responsible for phototopic vision, or colored vision. They have the ability to detect light at varying wavelengths and produce sharp images. Rods and cones lie along the retina in the back of the eye.
RP causes degeneration in rods and cones. This affects the optic nerve’s ability to convert light into electrical signals to send to the brain for processing.
In the early stages, the rod cells degenerate, making it hard to see in the dark. This gradually produces a loss of peripheral vision. As the disorder progresses, those with RP begin to notice averse changes in their cone cells. The process eventually leads to permanent blindness.
Dr. Kang Zhang, professor of ophthalmology at UCSD, and his team used CRISPR/Cas9 to deactivate a master switch gene called Nrl and a downstream transcription factor called Nr2e3. By manipulating the activation of these genes, Zhang is able to program rod cells to become cone cells.
“Cone cells are less vulnerable to the genetic mutations that cause RP,” Zhang said in a press release. “Our strategy was to use gene therapy to make the underlying mutations irrelevant, resulting in the preservation of tissue and vision.”
CRISPR/Cas9 stands for “clustered regularly interspaced short palindromic repeats” and is known to be a powerful tool in genetic technology because it allows researchers to edit the genome by changing parts of the DNA sequence.
CRISPR/Cas9 is made up of two molecules: the enzyme Cas9 and gRNA, or guide RNA. The function of the gRNA is to find the specific location to be edited and bind to that sequence in the DNA.
Cas9 then comes along to cut the strands to create an opening for the DNA sequence to be altered. gRNA begins to add the complementary bases to the altered DNA sequence.
Zhang and his team’s experiment on mice affected by RP showed improvements in their rod and cone receptors. A similar study done by the National Eye Institute at the National Institutes of Health and presented similar results.
“Human clinical trials could be planned soon after completion of preclinical study. There is no treatment for RP so the need is great and pressing,” Zhang said, according to Science Daily. “In addition, our approach of reprogramming mutation-sensitive cells to mutation-resistant cells may have broader application to other human diseases, including cancer.”