Multiple studies have shown a direct correlation between exposure to sunlight and cataract formation. The solar-induced cataract,or brunescent cataract, is characterized by increased browning of the lens, which progressively removes a greater portionof the visible spectrum from reaching the retina. While this is the major cause of blindness in the world today, the mechanisms involved are poorly understood. The protein-bound chromophores present in aged human lenses are capable of absorbing UVA light (320-400 nm) and causing extensive protein damage due to the generation of reactive oxygen species (ROS). The work here proposes to quantitatively determine the ability of these isolated proteins to generate ROS and to document the increase in the formation of each of these ROS, and to document the increase in the formationof each of these ROS during aging and brunescent cataract formation. Since UVA irradiationcasues the oxidation of Trp and His residues and protein corsslinking, these properties will be determined in brunescent lenses to confirm the extend of UVA damage already extant inthese lenses. Further, the ability of specific scavengers and quenchers willbe employed in vitro to determine their ability to penetrate into the protein aggregates isolated from the lenses, as they may be effective as preventative agents inthe formation of solar cataracts.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY002035-21
Application #
2372508
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1982-09-30
Project End
2001-07-31
Budget Start
1997-08-01
Budget End
1998-07-31
Support Year
21
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Missouri-Columbia
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
112205955
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
Ortwerth, B J; James, H L (1999) Lens proteins block the copper-mediated formation of reactive oxygen species during glycation reactions in vitro. Biochem Biophys Res Commun 259:706-10

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