Many epidemiological studies implicate increased exposure to sunlight as a risk factor for cataract. Initial data argued that UVB light was the damaging element in sunlight, which was confirmed by animal studies. UVA light, while having no effect on rodent lenses, is increasingly being implicated in human cataract. This discrepancy arises from the fact that human lenses accumulate """"""""yellow"""""""" protein modifications with aging, and these modified amino acids absorb UVA light. UVA light, which is completely absorbed by the human lens, has the potential to produce damaging oxygen free radicals. This is not a problem in young lenses due to the low oxygen content, but appears to be a significant damaging reaction in cataract lenses. There have been almost no investigations on the effects of UVA light on the lens constituents. Several candidate compounds will be analyzed for their ability to produce oxygen free radicals and for the oxidation of lens antioxidants. We have isolated and determined the structure of several novel """"""""yellow"""""""" compounds from human lens. These compounds are photo-bleached by UVA light. The structure of the bleached compounds and the levels of these bleached compounds in human lens and cataracts will be determined. This will be a direct demonstration of UVA effects in lens tissue. Brunescent cataracts are characterized by intense browning and are a major cataract pathology tropical countries. This is likely due to an accumulation of tryptophan oxidation products in the lens proteins. Since we know that the tryptophan content of the lens is decreased in brunescent cataract, we will also determine the structure of the trp oxidation products in vitro by the UVA irradiation of human lens proteins. The content of these oxidation products will be analyzed in brunescent lenses from India to also document UVA damage in these lenses. Direct measurements of the various tryptophan oxidation products formed due to the exposure of lens proteins to singlet oxygen and to hydrogen peroxide will be made in order to identify which is the major damaging reactive oxygen species in brunescent cataract.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY002035-28
Application #
6817029
Study Section
Special Emphasis Panel (ZRG1-AED (01))
Program Officer
Liberman, Ellen S
Project Start
1982-09-30
Project End
2007-07-31
Budget Start
2004-08-01
Budget End
2005-07-31
Support Year
28
Fiscal Year
2004
Total Cost
$245,396
Indirect Cost
Name
University of Missouri-Columbia
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
153890272
City
Columbia
State
MO
Country
United States
Zip Code
65211
Ortwerth, Beryl J; Bhattacharyya, Jaya; Shipova, Ekaterina (2009) Tryptophan metabolites from young human lenses and the photooxidation of ascorbic acid by UVA light. Invest Ophthalmol Vis Sci 50:3311-9
Linetsky, Mikhail; Shipova, Ekaterina; Cheng, Rongzhu et al. (2008) Glycation by ascorbic acid oxidation products leads to the aggregation of lens proteins. Biochim Biophys Acta 1782:22-34
Bhattacharyya, Jaya; Shipova, Ekaterina V; Santhoshkumar, Puttur et al. (2007) Effect of a single AGE modification on the structure and chaperone activity of human alphaB-crystallin. Biochemistry 46:14682-92
Argirov, O K; Lin, B; Ortwerth, B J (2005) Phototransformations of advanced glycation end products in the human eye lens due to ultraviolet A light irradiation. Ann N Y Acad Sci 1043:166-73
Cheng, Rongzhu; Feng, Qi; Argirov, Ognyan K et al. (2005) K2P--a novel cross-link from human lens protein. Ann N Y Acad Sci 1043:184-94
Linetsky, Mikhail; Chemoganskiy, Vitaliy G; Hu, Fang et al. (2003) Effect of UVA light on the activity of several aged human lens enzymes. Invest Ophthalmol Vis Sci 44:264-74
Ortwerth, Beryl J; Chemoganskiy, Vitaliy; Mossine, Valeri V et al. (2003) The effect of UVA light on the anaerobic oxidation of ascorbic acid and the glycation of lens proteins. Invest Ophthalmol Vis Sci 44:3094-102
Ortwerth, Beryl J; Chemoganskiy, Vitaliy; Olesen, P R (2002) Studies on singlet oxygen formation and UVA light-mediated photobleaching of the yellow chromophores in human lenses. Exp Eye Res 74:217-29
Linetsky, M; LeGrand, R D; Mossine, V V et al. (2001) Sugar-mediated crosslinking of alpha-biotinylated-Lys to cysteamine-agarose support: a method to isolate Maillard Lys-Lys-like crosslinks. Appl Biochem Biotechnol 94:71-96
Linetsky, M; James, H L; Ortwerth, B J (1999) Spontaneous generation of superoxide anion by human lens proteins and by calf lens proteins ascorbylated in vitro. Exp Eye Res 69:239-48

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