The goal of the proposed work is to define the molecular mechanisms underlying age pigment accumulation in the mammalian retinal pigment epithelium (RPE). This goal will be achieved by determining the chemical structures of the molecules responsible for age pigment autofluorescence. In addition, it will be determined whether experimental manipulations can affect composition and rates of autofluorescent pigment deposition in the RPE. The latter experiments will reveal the significance of various physiological factors in determining the extent of age pigment accumulation in the RPE. Chemical characterization of age pigment will be performed on pigment granules isolated from the RPE of human donor eyes. The fluorophores will be extracted from these granules, separated and purified by various chromatographic techniques, and structurally identified using standard analytical techniques including mass, nuclear magnetic resonance, uv-vis and ir absorbance and corrected fluorescence spectroscopic techniques. Spectral and chromatographic behaviors will be utilized in the development of qualitative and quantitative assays for specific fluorescent components of the lipofuscin granules. Animal experiments will be conducted to determine whether antioxidant nutrient status, vitamin A intake, light exposure, and phagocytosis influence the chemical composition and rates of deposition of lipofuscin in the RPE. The effects of the latter manipulations will be evaluated by quantitative microscopic and chemical assay procedures. It is possible that age pigment accumulation or the reactions leading to its formation may be detrimental to RPE function. Such effects may ultimately lead to senile macular degeneration. Understanding the mechanisms underlying age pigment accumulation may suggest means by which to prevent development of the latter disease.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY006458-02
Application #
3262586
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1986-04-01
Project End
1989-03-31
Budget Start
1987-04-01
Budget End
1988-03-31
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Missouri-Columbia
Department
Type
Schools of Medicine
DUNS #
112205955
City
Columbia
State
MO
Country
United States
Zip Code
65211
Katz, M L; Christianson, J S; Gao, C L et al. (1994) Iron-induced fluorescence in the retina: dependence on vitamin A. Invest Ophthalmol Vis Sci 35:3613-24
Katz, M L; Stientjes, H J; Gao, C L et al. (1993) Iron-induced accumulation of lipofuscin-like fluorescent pigment in the retinal pigment epithelium. Invest Ophthalmol Vis Sci 34:3161-71
Katz, M L; White, H A; Gao, C L et al. (1993) Dietary restriction slows age pigment accumulation in the retinal pigment epithelium. Invest Ophthalmol Vis Sci 34:3297-302
Katz, M L; Gao, C L; Stientjes, H J (1993) Regulation of the interphotoreceptor retinoid-binding protein content of the retina by vitamin A. Exp Eye Res 57:393-401
Katz, M L; Norberg, M (1992) Influence of dietary vitamin A on autofluorescence of leupeptin-induced inclusions in the retinal pigment epithelium. Exp Eye Res 54:239-46
Katz, M L; Kutryb, M J; Norberg, M et al. (1991) Maintenance of opsin density in photoreceptor outer segments of retinoid-deprived rats. Invest Ophthalmol Vis Sci 32:1968-80
Katz, M L; Rodrigues, M (1991) Juvenile ceroid lipofuscinosis. Evidence for methylated lysine in neural storage body protein. Am J Pathol 138:323-32
Katz, M L; Shanker, M J (1989) Development of lipofuscin-like fluorescence in the retinal pigment epithelium in response to protease inhibitor treatment. Mech Ageing Dev 49:23-40
Katz, M L; Eldred, G E (1989) Retinal light damage reduces autofluorescent pigment deposition in the retinal pigment epithelium. Invest Ophthalmol Vis Sci 30:37-43
Katz, M L (1989) Incomplete proteolysis may contribute to lipofuscin accumulation in the retinal pigment epithelium. Adv Exp Med Biol 266:109-16;discussion 116-8

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