Usha P. Andley Pages 887 - 892 ( 6 )
The development of cataracts is a debilitating eye condition which is common in elderly patients and afflicts millions worldwide. Cataracts result from the deposition of aggregated proteins in the eye which causes clouding of the lens, light scattering, and obstruction of vision. Non-syndromic, hereditary human cataract development is linked to point mutations in the CRYAA and CRYAB genes which encode αA and αB-crystallin. The α-crystallins are small heat shock proteins which play central roles in maintaining lens transparency and refractive properties. The discovery in 1992 that these proteins possess chaperone-like activity has led most researchers to focus on the ability of α-crystallins to prevent protein aggregation in vitro. While the ability of α- crystallins to efficiently trap aggregation-prone denatured proteins in vitro is thought to delay the development of age-related cataracts in vivo, α-crystallins have additional functions which may also contribute to cataract pathology. In addition to chaperone activity, α-crystallins are known to protect cells from stress-induced apoptosis, regulate cell growth, and enhance genomic stability. They also physically and functionally interact with both the cell membrane and cytoskeleton. Functional changes in α-crystallin have been shown to modify membrane and cell-cell interactions and lead to lens cell pathology in vivo. This article focuses on the multiple diverse roles of αA-crystallin in the maintenance of lens function and cataract development in vivo.
Alpha-crystallin, lens, protein aggregation, cataracts, mutation, hereditary cataract
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, 660 S. Euclid Avenue, Campus Box 8096, St. Louis,Missouri 63110, USA.