Cataracts cloud the vision of nearly everyone sooner or later. Finding out what goes wrong in the lens of the eye could help prevent this common problem, particularly for those who inherit an early onset of the condition. New research shows that without a certain DNA-chomping molecule in their eyes, mice develop cataracts. Defects in this molecule may also contribute to human cataracts.
Light can pass through the lens because the cells break down their internal structures during development. Even so, these cells aren't simply empty; they house a highly organized network of proteins called crystallins that transmit and focus the light passing through. Any disruption in this sophisticated scaffolding can cloud the lens, causing cataracts. Most often, this happens with age, but certain congenital conditions lead to cataracts early in life. Researchers have identified genetic mutations responsible for some of these youthful cases, but they didn't know exactly what the mutations did. In fact, no one even knew which enzymes are essential to ensuring a transparent lens.
Probing the cells of the lens, molecular geneticist Shigekazu Nagata of Osaka University, Japan, and his colleagues detected large amounts of an enzyme called DLAD, which chops up DNA. The researchers genetically engineered mice to lack DLAD. At first glance, the modified mice had apparently normal eyes: The lens cells had lost their nuclei and other internal structures. However, when the researchers looked closer, they found clumps of DNA in the animals' lens cells that clouded their lenses. The finding, reported in the 28 August issue of Nature, reveals that DNA alone can interfere with vision, even if the rest of the cells' innards disappear. Humans also make the DNA-munching enzyme, but it remains to be seen whether it serves the same purpose in our eyes as in mice.
Although additional molecules will certainly play a role in breaking down the nuclei, "this is clearly a key enzyme," says cell biologist Steven Bassnett of Washington University in St. Louis, Missouri. He calls the paper "a good demonstration" of what scientists have long supposed--that cataracts result when the cell's internal structures fail to disintegrate properly. This enzyme, Bassnett adds, will be an obvious candidate for investigating inherited cataracts in humans.