Abstract

The long-term objective of this research is to provide a biochemical mechanism for cataract caused by an overdose of the essential trace mineral, selenium. Experiments will be performed to test our working hypothesis for the mechanism of selenite cataract. This hypothesis states that the association of selenium with critical lens proteins in the epithelium or lens bow region initiates a chain of events leading to accumulation of calcium in the nucleus and subsequent nuclear opacity. Four experiments will study: 1) the association of 75Se with lens proteins, 2) the effect of selenium on lens proteins, 3) the role of calcium in selenite cataractogenesis, and 4) the histological basis of selenite cataract. When possible, human lenses will be subjected to studies performed on rat lenses. Not only will these studies provide a biochemical basis for selenite cataract, but they will provide a study system for measuring the role of calcium in cataractogenesis, devoid of changes in lens sodium, potassium, and water. Hopefully, these model studies will help to understand and prevent cataractogenesis in man.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY003600-04
Application #
3257964
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1981-09-30
Project End
1987-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
4
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Oregon Health and Science University
Department
Type
Schools of Dentistry/Oral Hygn
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239

  Publications

Azuma, Mitsuyoshi; Tamada, Yoshiyuki; Kanaami, Sayaka et al. (2003) Differential influence of proteolysis by calpain 2 and Lp82 on in vitro precipitation of mouse lens crystallins. Biochem Biophys Res Commun 307:558-63
Kim, Yung Hae; Kapfer, Deborah M; Boekhorst, Jos et al. (2002) Deamidation, but not truncation, decreases the urea stability of a lens structural protein, betaB1-crystallin. Biochemistry 41:14076-84
Lampi, Kirsten J; Shih, Marjorie; Ueda, Yoji et al. (2002) Lens proteomics: analysis of rat crystallin sequences and two-dimensional electrophoresis map. Invest Ophthalmol Vis Sci 43:216-24
Nakajima, Takeshi; Nakajima, Emi; Fukiage, Chiho et al. (2002) Differential gene expression in the lens epithelial cells from selenite injected rats. Exp Eye Res 74:231-6
Lampi, Kirsten J; Kim, Yung H; Bachinger, Hans Peter et al. (2002) Decreased heat stability and increased chaperone requirement of modified human betaB1-crystallins. Mol Vis 8:359-66
Tamada, Y; Fukiage, C; Mizutani, K et al. (2001) Calpain inhibitor, SJA6017, reduces the rate of formation of selenite cataract in rats. Curr Eye Res 22:280-5
Shih, M; David, L L; Lampi, K J et al. (2001) Proteolysis by m-calpain enhances in vitro light scattering by crystallins from human and bovine lenses. Curr Eye Res 22:458-69
Nakamura, Y; Fukiage, C; Azuma, M et al. (2001) Calpain-induced light scattering in young rat lenses is enhanced by UV-B. J Ocul Pharmacol Ther 17:47-58
Lampi, K J; Oxford, J T; Bachinger, H P et al. (2001) Deamidation of human beta B1 alters the elongated structure of the dimer. Exp Eye Res 72:279-88
Shearer, T R; Ma, H; Shih, M et al. (2000) Calpains in the lens and cataractogenesis. Methods Mol Biol 144:277-85

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