Abstract

The overall objective of the proposed research is to determine the mechanism underlying the age-related accumulation of the autofluorescent pigment lipofuscin in the retinal pigment epithelium (RPE) and whether lipofuscin plays a role in age-related retinal diseases. A central focus is to better understand how vitamin A participates in RPE lipofuscin generation, including the possibility that retinal modification of rod outer segment (ROS) proteins accounts for a significant fraction of RPE lipofuscin.
Three specific aims are proposed: (1) determine the molecular composition of human RPE lipofuscin; (2) determine whether RPE lipofuscin constituents turn over; and (3) determine whether light exposure to the retina promotes lipofuscin accumulation in the RPE.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY008813-06
Application #
2459126
Study Section
Visual Sciences C Study Section (VISC)
Project Start
1991-01-01
Project End
1999-07-31
Budget Start
1997-08-01
Budget End
1999-07-31
Support Year
6
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
University of Missouri-Columbia
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
112205955
City
Columbia
State
MO
Country
United States
Zip Code
65211

  Publications

Robison Jr, W G; Jacot, J L; Katz, M L et al. (2000) Retinal vascular changes induced by the oxidative stress of alpha-tocopherol deficiency contrasted with diabetic microangiopathy. J Ocul Pharmacol Ther 16:109-20
Riis, R C; Jackson, C; Rebhun, W et al. (1999) Ocular manifestations of equine motor neuron disease. Equine Vet J 31:99-110
Katz, M L; Rice, L M; Gao, C L (1999) Reversible accumulation of lipofuscin-like inclusions in the retinal pigment epithelium. Invest Ophthalmol Vis Sci 40:175-81
Katz, M L; Gao, C L; Rice, L M (1999) Long-term variations in cyclic light intensity and dietary vitamin A intake modulate lipofuscin content of the retinal pigment epithelium. J Neurosci Res 57:106-16
Liou, G I; Matragoon, S; Chen, D M et al. (1998) Visual sensitivity and interphotoreceptor retinoid binding protein in the mouse: regulation by vitamin A. FASEB J 12:129-38
Katz, M L; Gao, C L; Rice, L M (1996) Formation of lipofuscin-like fluorophores by reaction of retinal with photoreceptor outer segments and liposomes. Mech Ageing Dev 92:159-74
Prabhakaram, M; Katz, M L; Ortwerth, B J (1996) Glycation mediated crosslinking between alpha-crystallin and MP26 in intact lens membranes. Mech Ageing Dev 91:65-78
Katz, M L; Gao, C L (1995) Vitamin A incorporation into lipofuscin-like inclusions in the retinal pigment epithelium. Mech Ageing Dev 84:29-38
Katz, M L; Christianson, J S; Norbury, N E et al. (1994) Lysine methylation of mitochondrial ATP synthase subunit c stored in tissues of dogs with hereditary ceroid lipofuscinosis. J Biol Chem 269:9906-11
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

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