Presbyopia and heat: changes associated with aging of the human lens suggest a functional role for the small heat shock protein, alpha-crystallin, in maintaining lens flexibility.
Presbyopia, the inability to focus up close, affects everyone by age 50 and is the most common eye condition. It is thought to result from changes to the lens over time making it less flexible. We present evidence that presbyopia may be the result of age-related changes to the proteins of the lens fibre cells. Specifically, we show that there is a progressive decrease in the concentration of the chaperone, alpha-crystallin, in human lens nuclei with age, as it becomes incorporated into high molecular weight aggregates and insoluble protein. This is accompanied by a large increase in lens stiffness. Stiffness increases even more dramatically after middle age following the disappearance of free soluble alpha-crystallin from the centre of the lens. These alterations in alpha-crystallin and aggregated protein in human lenses can be reproduced simply by exposing intact pig lenses to elevated temperatures, for example, 50 degrees C. In this model system, the same protein changes are also associated with a progressive increase in lens stiffness. These data suggest a functional role for alpha-crystallin in the human lens acting as a small heat shock protein and helping to maintain lens flexibility. Presbyopia may be the result of a loss of alpha-crystallin coupled with progressive heat-induced denaturation of structural proteins in the lens during the first five decades of life.
Heys
Karl R
KR
Save Sight Institute, University of Sydney, Sydney, NSW 2001, Australia.
Friedrich
Michael G
MG
Truscott
Roger J W
RJ
D000375:Aging / Q000378:metabolism*; D000818:Animals; D050888:Heat-Shock Proteins, Small / Q000032:analysis / Q000172:deficiency*; D006358:Hot Temperature; D006801:Humans; D007908:Lens, Crystalline / Q000737:chemistry / Q000378:metabolism*; D008875:Middle Aged; D018583:Pliability; D011305:Presbyopia / Q000209:etiology* / Q000378:metabolism; D013552:Swine; D038201:alpha-Crystallins / Q000032:analysis / Q000172:deficiency*
D050888:Heat-Shock Proteins, Small; D038201:alpha-Crystallins