Presbyopia and heat:: changes associated with aging of the human lens suggest a functional role for the small heat shock protein, α-crystallin, in maintaining lens flexibility

被引:109
作者
Heys, Karl R.
Friedrich, Michael G.
Truscott, Roger J. W. [1 ]
机构
[1] Univ Sydney, Save Sight Inst, Sydney, NSW 2001, Australia
[2] Univ Wollongong, Dept Chem, Wollongong, NSW 2522, Australia
关键词
aging; alpha-crystallin; lens stiffness; presbyopia; protein denaturation; thermal aggregation;
D O I
10.1111/j.1474-9726.2007.00342.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:807 / 815
页数:9
相关论文
共 54 条
[1]   RISE IN LENS TEMPERATURE ON EXPOSURE TO SUNLIGHT OR HIGH AMBIENT-TEMPERATURE [J].
ALGHADYAN, AA ;
COTLIER, E .
BRITISH JOURNAL OF OPHTHALMOLOGY, 1986, 70 (06) :421-426
[2]  
Augusteyn RC, 2006, MOL VIS, V12, P740
[3]  
BORCHMAN D, 1994, INVEST OPHTH VIS SCI, V35, P3938
[4]   AGE-RELATED-CHANGES IN WATER AND CRYSTALLIN CONTENT OF THE FETAL AND ADULT HUMAN LENS, DEMONSTRATED BY A MICROSECTIONING TECHNIQUE [J].
BOURS, J ;
FODISCH, HJ ;
HOCKWIN, O .
OPHTHALMIC RESEARCH, 1987, 19 (04) :235-239
[5]   CHANGE IN SHAPE AND INTERNAL FORM OF LENS OF EYE ON ACCOMMODATION [J].
BROWN, N .
EXPERIMENTAL EYE RESEARCH, 1973, 15 (04) :441-459
[6]  
BRUCKNER R, 1986, DOC OPHTHALMOL, V64, P235
[7]   Structure elucidation of a novel yellow chromophore from human lens protein [J].
Cheng, RZ ;
Feng, Q ;
Argirov, OK ;
Ortwerth, BJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (44) :45441-45449
[8]   CHANGES IN DISTRIBUTION OF PROTEINS IN AGING HUMAN LENS [J].
COGHLAN, SD ;
AUGUSTEYN, RC .
EXPERIMENTAL EYE RESEARCH, 1977, 25 (06) :603-611
[9]   UNIFIED MODEL FOR ACCOMMODATIVE MECHANISM [J].
COLEMAN, DJ .
AMERICAN JOURNAL OF OPHTHALMOLOGY, 1970, 69 (06) :1063-&
[10]   α-crystallin as a molecular chaperone [J].
Derham, BK ;
Harding, JJ .
PROGRESS IN RETINAL AND EYE RESEARCH, 1999, 18 (04) :463-509