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UCLA researchers identify key enzyme linked to childhood blindness

In findings that could lead to curing some forms of congenital blindness through gene therapy, researchers at 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. The identity of this enzyme has long been a mystery to scientists.

The study, "Rpe65 is the Retinoid Isomerase in Bovine Retinal Pigment Epithelium," is published in the Aug. 12 issue of Cell magazine.

"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's Jules Stein Eye Institute and one of the researchers. "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 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 percep
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Source:University of California - Los Angeles


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