Combining the expertise of several different labs, University of Iowa researchers have found a new genetic cause of the blinding eye disease retinitis pigmentosa (RP) and, in the process, discovered an entirely new version of the message that codes for the affected protein.
The study, which was published online August 8 in the Proceedings of the National Academy of Sciences (PNAS) Early Edition, suggests that the mutation may be a significant cause of RP in people of Jewish descent. The findings also lay the groundwork for developing prevention and treatment for this form of RP using a combination of genetic testing, gene therapy and cell replacement approaches.
Using the latest DNA sequencing techniques to analyze the protein-coding regions of a single RP patient’s genome, the researchers found a mutation in a gene called MAK (male germ cell associated kinase). This gene had not previously been associated with eye disease in humans. However, examining tissue from donated eyes showed that MAK protein was located in the parts of the retina that are affected by the disease.
The researchers then generated induced pluripotent stem cells (iPSCs) from the patient’s own skin cells and coaxed these immature cells to develop into retinal tissue. Analyzing this tissue showed that the gene mutation caused the loss of the MAK protein in the retina.
“These new technologies have greatly enhanced our ability to find and validate disease-causing mutations, which is critical to our ability to progress to the next step of actually treating diseases like RP,” said Budd Tucker, PhD, UI assistant professor of ophthalmology and visual science and lead study author.
Based on the new work, the UI team hopes to explore gene therapy and cell replacement strategies as potential therapies for this form of RP.