Discovery of new genetic mutations associated with childhood blindness
The discovery of new genetic mutations associated with childhood blindness, achieved through a collaboration between teams led by Michel Cayouette at the IRCM, Robert K. Koenekoop at McGill University and Doris Kretzschmar at Oregon Health and Science University has recently been published. The researchers identified a novel link between retinal degeneration and lipid metabolism. Results of their study could pave the way to new treatments for retinal degenerative diseases like Olive McFarlane syndrome (OMS) and Leber’s congenital amaurosis (LCA).
By attempting to uncover the genetic causes of OMS, a rare disease characterized by a degeneration of the retina that causes vision loss at a very young age, the researchers identified mutations in the gene PNPLA6 that are involved in lipid metabolism.
“This breakthrough is important because it represents the first discovery of a genetic mutation associated with this disease,” says Michel Cayouette, PhD, Director of the Cellular Neurobiology research unit at the IRCM. “In addition, we discovered that this same gene also affects patients with LCA.”
“We found that the gene plays an important role in the survival of photoreceptors, a specialized type of light-sensing neurons found in the retina,” explains Vasanth Ramamurthy, PhD, co-first author of the study in Dr. Cayouette’s laboratory. “More specifically, our results show that mutations in the gene lead to photoreceptor death, which, in turn, causes blindness in children with OMS and LCA.”
The scientists also discovered the lipid metabolism was altered in photoreceptors, thereby identifying a potential new target for the development of drugs that could treat retinal degeneration in patients with OMS and LCA.
“At the IRCM, we started a new research project to produce a mouse model of the mutation in order to better understand the molecular causes of these pathologies,” adds Dr. Cayouette. “This model will also allow us to test different therapeutic approaches to determine, for example, whether manipulating lipid metabolism could prevent retinal degeneration.” IRCM
