November 14, 1997
Researchers find gene causing vision loss
TORONTO - An international team of researchers, led by Dr. Roderick McInnes of The Hospital for Sick Children (SickKids), has identified a gene in which mutations cause inherited retinal degeneration. The work was done in collaboration with Drs. Shomi Bhattacharya of University College, London, Constance Cepko of Harvard Medical School, and Samuel Jacobson of the University of Pennsylvania. The research is published in today's issue of the scientific journal Cell.
The research team has found that a mutation in the new gene, called CRX, causes cone-rod dystrophy, a condition which leads to the degeneration of the retina's light-sensing cells, the photoreceptors. Photoreceptors convert light energy into nerve impulses. Cones are the cells responsible for colour perception and fine vision; rods govern vision in low light.
Cone-rod dystrophy takes many years to develop, but ultimately causes total blindness. The CRX gene mutations were found in two familes, one from the United States and the other from Greece.
"While cone-rod dystrophy is relatively rare, as in many genetic discoveries the identification of the gene has broad significance," explains Dr. McInnes, Director of the Developmental Biology research program at The Hospital for Sick Children and Professor of Paediatrics at the University of Toronto. "It's a major step along the road to understanding how photoreceptors develop and are maintained. We suspect that this gene may also be involved in other inherited diseases which lead to the degeneration of cones and rods, such as Retinitis Pigmentosa."
Dr. McInnes also suspects that CRX may be a modifier gene. "Modifier genes regulate the severity of genetic diseases," he explains. Thus, the action of the CRX gene may explain why two individuals in the same family, each with the same inherited disease of the retina, may have very different rates of visual loss.
In an accompanying paper in the same issue of Cell, Dr. Cepko and her colleagues demonstrated that the CRX gene controls many other important genes in the photoreceptors, and that without a functioning CRX gene, the photoreceptors don't develop normally.
The current research builds on the discovery by Dr. McInnes last year of an eye development gene in the mouse, called CHX10. The discovery of the mouse gene led them to the CRX gene in humans. Dr. McInnes and his colleagues reasoned that since CHX10 was important for the normal development and function of the retina, that a search for new genes related to CHX10 might identify additional important eye disease genes. CRX was one of the CHX10 relatives discovered by this search. Dr. Cepko and her colleagues independently discovered the CRX gene using a similar strategy.
Collaborators in the research at The Hospital for Sick Children included Drs. Carol Freund, Stephen Scherer, and Lap-Chee Tsui.
This research is supported by grants from the Foundation Fighting Blindness, the RP Foundation of Canada and the Canadian Genetic Diseases Network.
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