Dimmed vision. In this three-dimensional rendering of a cone cell, red indicates that mTOR surplus phosphates, an indication that the cell dies of hunger.
Claudio Punzo
Rod cells in our eyes help us see in dim light. They also ensure that the cones, other light-sensitive cells on which we depend for vision, enough food, a new study reveals. The findings may shed light on a common cause of blindness.
Approximately 100,000 people in the United States have retinitis pigmentosa, a hereditary retinal incurable disease that leads to blindness. Over 40 genes may contribute to disease, often damaging important proteins in the cells of the retina. initial symptom loss, night vision disease, occurs when stems begin to die off. This attrition usually begins in childhood, and even if it is inconvenient, most people get by with their cones - the photoreceptor cells that operate in bright light. But when those affected reach adulthood, the cones begin to die, too, ultimately resulting in total blindness. This has confused the scientists, because defective genes are not active in the cones, as in the stems.
To crack this mystery, Constance Cepko biologist from Harvard University and his colleague Claudio Punzo, a postdoctoral researcher, first evaluated earlier theories. Some researchers believe that when the stems are dead, they produced a toxin that killed cones. Others have speculated that, because the stems use a lot of oxygen in the retina, their death could leave a large amount of oxygen that overloads and damages the remaining cones. But none of them seemed to match the trend, Cepko said, so he and Punzo decided to look for a new explanation.
The researchers measured the activity of genes in four different strains of mice with defective stem cells. They found more than 0 genes that are activated at about the same time, the cones began to die, many of them related to cell metabolism.
"That was our first clue that maybe the cells do not receive enough nutrients," says Cepko. Several of these genes were linked to a protein known as the mammalian target of rapamycin, or mTOR, which leaves the cell whether it has enough nutrients. - especially glucose But if the harsh famine long enough, mTOR directs the cell to digest is exactly what the cones were
[in determining whether a drop-off glucose was killing cones, the researchers injected abdominally some of the mice with insulin to increase their glucose levels. the shots do not cause the cones to hang on a little longer long, but they still died a few weeks later.
Cepko and Punzo think the cones could starve because of crumbling architecture of the retina. a thin layer of cells, known as name of the retinal pigment epithelium (RPE), covers the rods and cones like a circus tent and provides their nutrients. Rods outnumber cones in the retina significantly, so that when they die, most of the "tent poles" of RpEs die with them. Collapses tents, cones lose their nutrient connection, and they starve slowly. The study is published online this week in Nature Neuroscience .
"I think it's very exciting," said Rafael Caruso, an ophthalmologist with the US National Eye Institute in Bethesda, Md. "It's a new approach to the problem." Caruso said researchers "do a pretty convincing case for their conclusions," especially because the same mutations in mice tested are also found in humans.
Unfortunately, both Cepko Caruso and agree that the finding does little to researchers seeking treatments. But it suggests a new framework for thinking about the problem. Exploring different ways to get nutrients into the cones, Cepko said, researchers may one day be able to help people with retinitis pigmentosa retain their daytime vision for a longer period of time.
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