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Sight to the blind

点击量:   时间:2019-02-26 12:01:01

By Ian Anderson THE discovery of two mutant genes in people suffering from an inherited disease of the retina may open up the way to a treatment. This could prevent as many as a million people worldwide from going blind, researchers say. The disease, retinitis pigmentosa (RP), causes the steady degeneration of the light-detecting cells of the retina. It normally strikes children and young adults, leading to night blindness, tunnel vision and eventually to total blindness in adulthood. Over the past eight years, research teams led by molecular geneticist Mike Denton of the University of Otago in New Zealand and Andreas Gal of the Institute for Human Genetics in Hamburg have collected blood samples from members of 20 Indian families that carry the disease. “The families are ideal for the genetic mapping of inherited diseases because of the tremendous amount of inbreeding,” says Denton. Marriages of first cousins and of uncle to niece are common in India. In one family from Kerala, Denton’s team found a mutation in a protein that normally binds to retinaldehyde, a small molecule that is derived from vitamin A. Because the mutated protein loses its ability to bind, less retinaldehyde is converted into a form that the photoreceptor cells can use to detect light. In two other families, from Bangalore and Madras, and three German families, Gal’s group found a mutation in the RPE65 protein, which is believed to be involved in the transport of vitamin A from the blood to the retina. Neither of the two mutations was found in families that are free of the disease. The results, which the teams report in a series of papers in this month’s Nature Genetics(vol 29, p 194), confirm that vitamin A supplements should be an effective treatment for the disease by helping the photoreceptor cells to function. “Night blindness has been treated for centuries with liver extracts containing vitamin A,” Denton says. “RP sufferers also have received vitamin A, but until now this has been done with limited scientific basis.” The researchers say that the best news, however, is that both mutations are only expressed in the epithelium. This is a layer of cells that coats the back of the eye. Until now, the only known genetic defects linked to RP have been expressed in the neuroretina, a more complex structure that contains the eye’s photoreceptor cells. This is much harder to treat than the epithelium, according to the researchers. “This is a very exciting result with a great deal of medical significance,” Denton says. “The epithelium is simple in structure and highly suitable for transplantation.” A research group in Hyderabad in India, using fetal cells, has already shown that it is possible to transplant epithelial cells, Denton adds. However, he does not expect transplantation to be available as a routine treatment for up to 10 years. Jane Farrar, a geneticist at Trinity College in Dublin who has studied RP for ten years, points out that the newly identified genes are likely to be involved in only a small proportion of cases of RP. Denton has estimated that the epithelial mutations are responsible in only between 5 and 25 per cent of the 4 million RP sufferers worldwide. However, Farrar says,