Researchers have achieved dynamic, atomic-scale views of a protein needed to maintain the transparency of the lens in the human eye. The work, funded in part by the National Institutes of Health, could lead to new insights and drugs for treating cataract and a variety of other health conditions.
Aquaporin proteins form water channels between cells and are found in many tissues, but aquaporin zero (AQP0) is found only in the mammalian lens, which focuses light onto the retina, at the back of the eye. The lens is primarily made up of unique cells called lens fibers that contain little else besides water and proteins called crystallins. Tight packing of these fibers and of the crystallin proteins within them helps create a uniform medium that allows light to pass through the lens, almost as if it were glass.
Abnormal development or age-related changes in the lens can lead to cataracta clouding of the lens that causes vision loss. Besides age, other risk factors for cataract include smoking, diabetes, and genetic factors. Mutations in the AQP0 gene can cause congenital cataract and may increase the risk of age-related cataract.
"The AQP0 channel is believed to play a vital role in maintaining the transparency of the lens and in regulating water volume in the lens fibers, so understanding the molecular details of how water flows through the channel could lead to a better understanding of cataract," said Dr. Houmam Araj, who oversees programs on lens, cataract and oculomotor systems at NIH's National Eye Institute (NEI), which helped fund the research.
Closing of AQP0 channels is regulated by a calcium-sensitive protein called calmodulin, but the precise mechanism has been unclear. Some models have suggested that calmodulin simply acts as a plug to fill the open channel. The new study, published in Nature Structural and Molecular Biology, reveals a more nuanced process in which calmodulin essentially grasps the open channe
|Contact: Jean Horrigan|
NIH/National Eye Institute