The long range goal of the proposed studies is to elucidate the mechanism of radiation cataractogenesis. To do so the work will focus on three aspects of the problem. 1. The site of the initial injury. 2. The nature of the injury. 3. The manner in which the injury is expressed as cataract. The hypothesis to be tested assigns the initial insult to the genome of the lens epithelial cell. The cataract is the result of the expression of that injury during lens fiber differentiation. The studies directed at the first question will include preferential sensitization of the DNA of lens cell subpopulation using BrdU substitution techniques. Endocrinological intervention experiments are designed to dissect the roles of growth and differentiation in the radiation response. Investigations will be conducted to attempt to confirm that the bird lens, heretofore thought to be radioresistant, does develop radiocataracts. It appears that the unique anatomy, which accounts for the exaggerated period before lens epithelial cells become fibers, is responsible, thus corroborating the role of the epithelium in radiation cataract development. Radiation genotoxicity will be assayed by sister chromatid exchange and chromosomal aberration analyses. Both cytogenetic methods have been adapted by our laboratory to lens research. In addition the distinctive nature of heavy particle irradiation (500 MeV Argon) will be fully exploited to clarify the nature of other damage at the cellular and subcellular level. Cell kinetic and cytopathological studies willl aim at characterizing the nuances of the manner in which the affected epithelial cells transduce the injury into a clinically detectable opacity. The work will focus on perturbations in the lens epithelial cell cycle and differentiation. The latter aspect will be monitored by analyzing possible effects on the cytoskeleton and the crystallins within individual cells known to be damaged. The findings will contribute greatly to our understanding of cortical cataractogenesis of varying etiology, including age, and will have direct application in radiation risk assessments from radiation therapy, occupational exposure and in the space program.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY002648-09
Application #
3256956
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1978-09-01
Project End
1987-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
9
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027
Wu, B; Medvedovsky, C; Worgul, B V (1994) Non-subjective cataract analysis and its application in space radiation risk assessment. Adv Space Res 14:493-500
Holsclaw, D S; Rothstein, H; Medvedovsky, C et al. (1994) Modulating radiation cataractogenesis by hormonally manipulating lenticular growth kinetics. Exp Eye Res 59:291-6
Worgul, B V; Brenner, D J; Medvedovsky, C et al. (1993) Accelerated heavy particles and the lens. VII: The cataractogenic potential of 450 MeV/amu iron ions. Invest Ophthalmol Vis Sci 34:184-93
Brenner, D J; Medvedovsky, C; Huang, Y et al. (1993) Accelerated heavy particles and the lens. VIII. Comparisons between the effects of acute low doses of iron ions (190 keV/microns) and argon ions (88 keV/microns). Radiat Res 133:198-203
Tao, F; Medvedovsky, C; David, J et al. (1993) Accelerated heavy ions and the lens. IX. Late effects of LET and dose on cellular parameters in the murine lens. Int J Radiat Biol 64:103-11
Koniarek, J P; Worgul, B V (1992) Do heavy ions cause microlesions in cell membranes? Adv Space Res 12:417-20
Worgul, B V; David, J; Odrich, S et al. (1991) Evidence of genotoxic damage in human cataractous lenses. Mutagenesis 6:495-9
Brenner, D J; Medvedovsky, C; Huang, Y et al. (1991) Accelerated heavy particles and the lens. VI. RBE studies at low doses. Radiat Res 128:73-81
Medvedovsky, C; Worgul, B V (1991) Neutron effects on the lens. Radiat Res 128:S103-10
Krebs, W; Krebs, I; Worgul, B V (1990) Effect of accelerated iron ions on the retina. Radiat Res 123:213-9

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