Researchers at University of California Los Angeles ( UCLA ) have discovered that RPE65, a gene missing in infants born with the blinding disease Leber congenital amaurosis, is also a key enzyme in the visual cycle.
" 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 Gabriel Travis, at UCLA's Jules Stein Eye Institute and one of the researchers.
Leber congenital amaurosis is an inherited disease that is believed to cause up to 20 percent 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.
" 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," 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."
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.
Photo bleaching leaves the rhodopsin insensitive to light until the all trans retinaldehyde is converted, or "isomerized," back into 11 cis retinaldehyde, which completes the visual cycle. Scientists have for two decades been attempting to identify the retinoid isomerase enzyme that catalyzes this regeneration of 11 cis retinaldehyde. Scientists have also been stumped by the function of the Rpe65 protein .
The researchers are now studying the effects on retinoid isomerase activity of specific disease causing mutations in the RPE65 gene, which should provide more data on the cause of Leber congenital amaurosis and on how the Rpe65 protein works. The researchers are also examining the function of other proteins that work closely with Rpe65. Mutations in the genes for these interacting proteins are linked to other forms of human blindness.
Source: University of California Los Angeles, 2005