A recent study has shown that infants born with the blinding disease Leber congenital amaurosis are missing the gene known as RPE65. The importance of this well known gene was also finally realized as scientists demonstrated that the gene is also the retinoid isomerase enzyme key to the visual cycle.
It has taken nearly two decades for scientists to identify this enzyme and the function of the RPE65 protein. The researchers from the University of California in Loss Angeles (UCLA) hope the findings could lead to a cure for some forms of congenital blindness through gene therapy.
“We were amazed when we discovered the function for RPE65, and that RPE65 is the retinoid isomerase. It is a protein that all of us had known about for years,” said Dr Gabriel Travis, professor of ophthalmology and biological chemistry at UCLA. “It’s like searching the world for a treasure, then discovering it in your own back yard.”
Leber congenital amaurosis is an inherited disease that is believed to cause up to 20% of all cases of childhood blindness. It is caused by mutations in several different genes including RPE65. An important characteristic of this disease is that the light sensitive rod and cone cells remain intact in the retinas of Leber patients for a long time.
The newly identified isomerase enzyme plays a crucial role in the regeneration of rhodopsin visual pigment in the retina after light exposure. Rhodopsin contains a light absorbing molecule called 11 cis retinaldehyde, related to vitamin A, which is converted upon light absorption to all trans retinaldehyde in a process called photo bleaching. This conversion is the first step in visual perception.
“This suggests that replacement of RPE65 by gene therapy should correct the blindness in these children, as was observed in mice and dogs with RPE65 mutations,” Dr Travis said. “This is a major breakthrough in understanding the visual cycle. It has ramifications for several inherited blinding diseases caused by mutations in visual cycle genes.”