Near-ultraviolet light from sunlight is known to increase the risk of formation of human cortical cataracts. The mechanism of action of different wavelengths of near-UV radiation on the lens is unknown at present. The focus of this study is to quantitate the biological effectiveness of specific wavelengths of radiation between 297 and 400 nm on the lens and lens constituents. Action spectra for lens opacification by monochromatic wavelengths in UVB (297-320nm) and UVA (320-400 nm) will be determined under biologically meaningful conditions. Intact bovine and human lenses and homogenates will be used. Spectroscopic techniques and protein crosslinking will be used to assess the damage. Quantitative studies on the generation of specific reactive oxygen species will be done, to assess their role in photodamage at different wavelengths. Less than ten percent of UVB and 60 percent of UVA reaches the human lens epithelium in vivo. However, UVB and not UVA increased the risk of cortical cataract formation in a recent human epidemiological study. The biological effects of UVB and UVA radiation on lens epithelial cells are unknown at present. Quantitative action spectrum studies on the cell survival, synthesis of newly synthesized proteins and DNA damage in lens epithelial cells are planned in this study. These data will provide quantitative information on the biological effects of near-UV wavelengths on the epithelium. Normal human lenses of different ages (infant, young and old), and cataractous lens epithelia will be investigated to determine the mechanism of action of near-UV radiation of the human lens in vivo. The long-term objective of this proposal is to define a molecular mechanism for the changes in lens constituents and obtain a better understanding of the link between photodamage and human cataract formation.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY005681-14
Application #
2019501
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1984-05-01
Project End
2001-03-31
Budget Start
1997-04-01
Budget End
1998-03-31
Support Year
14
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Washington University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Hamilton, Paul D; Andley, Usha P (2018) In vitro interactions of histones and ?-crystallin. Biochem Biophys Rep 15:7-12
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Andley, Usha P; Goldman, Joshua W (2016) Autophagy and UPR in alpha-crystallin mutant knock-in mouse models of hereditary cataracts. Biochim Biophys Acta 1860:234-9
Makley, Leah N; McMenimen, Kathryn A; DeVree, Brian T et al. (2015) Pharmacological chaperone for ?-crystallin partially restores transparency in cataract models. Science 350:674-7
Andley, Usha P; Malone, James P; Townsend, R Reid (2014) In vivo substrates of the lens molecular chaperones ?A-crystallin and ?B-crystallin. PLoS One 9:e95507
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Andley, Usha P; Malone, James P; Hamilton, Paul D et al. (2013) Comparative proteomic analysis identifies age-dependent increases in the abundance of specific proteins after deletion of the small heat shock proteins ?A- and ?B-crystallin. Biochemistry 52:2933-48
Andley, Usha P; Hamilton, Paul D; Ravi, Nathan et al. (2011) A knock-in mouse model for the R120G mutation of *B-crystallin recapitulates human hereditary myopathy and cataracts. PLoS One 6:e17671
Andley, Usha P; Malone, James P; Townsend, R Reid (2011) Inhibition of lens photodamage by UV-absorbing contact lenses. Invest Ophthalmol Vis Sci 52:8330-41
Reilly, Matthew A; Andley, Usha P (2010) Quantitative biometric phenotype analysis in mouse lenses. Mol Vis 16:1041-6

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