A major goal of the proposed project is to elucidate the role of lens electrolytes, particularly the cations calcium and magnesium, in cataract development. Studies of causes and consequences of alterations in the ionic composition of the lens will focus on both the aging and cataractous lens since human cataract is chiefly an age related disease. It remains particularly important therefore to continue investigations which identify and characterize those biochemical alterations common to cataractous and mature noncataractous lenses. The influence of ions on physiologic processes susceptible to modification or known to undergo alterations in cataract will be investigated in normal cultured lenses as well as in the cell free system to thoroughly investigate the synergistic effects of the ions on each process. If the content of lens calcium and GSH are altered, for example, the potentially cytotoxic effects of calcium on GSH synthesis will be determined under conditions in which ion levels are carefully controlled and selectively altered. The direct contribution of ionic alterations to opacification will be assessed by monitoring lens opacities of experimental cataracts using a laser scanning system. Parameters such as degree or location of opacity can be correlated with changes in biochemical properties such as ion, substrate, or GSH levels to determine whether calcium elevation, for instance, is a unique or sufficient requirement for opacification or whether additional alterations are required. Experiments are also necessary to determine the effect of altering the ionic environment of lens proteins on the conformation of the crystallins since high molecular weight aggregates are potential light scattering centers. The process of aggregation in opaque regions of the intact lens as well as modification of tertiary protein structure prior to aggregation will be investigated using HPLC and difference absorption spectroscopy techniques.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY003681-06
Application #
3258102
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1981-05-01
Project End
1987-04-30
Budget Start
1986-05-01
Budget End
1987-04-30
Support Year
6
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Oakland University
Department
Type
Schools of Arts and Sciences
DUNS #
City
Rochester
State
MI
Country
United States
Zip Code
48309
Hightower, K; McCready, J (1997) The role of calcium in UVB-induced damage in irradiated ocular lenses. Photochem Photobiol 65:155-60
Hightower, K R (1995) The role of the lens epithelium in development of UV cataract. Curr Eye Res 14:71-8
Hightower, K R; McCready, J P; Borchman, D (1994) Membrane damage in UV-irradiated lenses. Photochem Photobiol 59:485-90
Hightower, K R (1994) A review of the evidence that ultraviolet irradiation is a risk factor in cataractogenesis. Doc Ophthalmol 88:205-20
Hightower, K; McCready, J (1994) Selenite-induced damage to lens membranes. Exp Eye Res 58:225-9
Hightower, K R; Reddan, J R; McCready, J P et al. (1994) Lens epithelium: a primary target of UVB irradiation. Exp Eye Res 59:557-64
Hightower, K; McCready, J (1993) Comparative effect of UVA and UVB on cultured rabbit lens. Photochem Photobiol 58:827-30
Hightower, K; McCready, J (1992) Physiological effects of UVB irradiation on cultured rabbit lens. Invest Ophthalmol Vis Sci 33:1783-7
Hightower, K; McCready, J (1992) Mechanisms involved in cataract development following near-ultraviolet radiation of cultured lenses. Curr Eye Res 11:679-89
Hightower, K R; McCready, J P (1991) Effect of selenite on epithelium of cultured rabbit lens. Invest Ophthalmol Vis Sci 32:406-9

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