The overall objective of this project is to elucidate the mechanisms governing wound repair in the corneal endothelium. The central hypothesis to be explored in the proposed studies, is that arachidonate derived lipid mediators synthesized in response to injury or to extracellular signals modulate the progression of the corneal endothelial cell through its cycle of mitosis and differentiation.
The aims of the proposed study are to: 1) identify the modulatory lipid mediators of the corneal endothelium, 2) characterize the production of such mediators by mitotic and differentiating endothelial cells, 3) determine if receptor-dependent signal transduction is regulated in mitotic and differentiated endothelial cells, 4) explore post-receptor signal signal effector pathways that govern lipid mediator regulation of mitosis and differentiation in corneal endothelial cells and 5) compare lipid mediated regulation of mitosis and differentiation in rabbit human corneal endothelial cells. These questions will be investigated using mitotic, differentiated and wound closure models of rabbit corneal endothelial cells grown in tissue culture, and using organ culture models of human corneal endothelium. Lipid mediators regulating mitosis and differentiation will be identified using cyctochemical detection of cell cycle and differentiation markers. Biosynthesis of mediators and regulation of receptor mediated events will be determined using biochemical tracers, immunoassay of biosynthetic enzymes and biochemical assay of second messengers. The involvement of intracellular effector pathways will be investigated using pharmacological probes to alter signal transduction pathways. Lipid mediators found to alter mitosis and differentiation of rabbit corneal endothelium will also be tested using organ culture models of and dystrophic human corneal endothelium. The results obtained from these studies will suggest therapeutic strategies for enhancing corneal endothelial wound repair subsequent to accidental or surgical trauma.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY009437-02
Application #
3266877
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1992-01-01
Project End
1996-12-31
Budget Start
1993-01-01
Budget End
1993-12-31
Support Year
2
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Louisville
Department
Type
Schools of Medicine
DUNS #
City
Louisville
State
KY
Country
United States
Zip Code
40292
Jumblatt, M M (1997) PGE2 synthesis and response pathways in cultured corneal endothelial cells: the effects of in vitro aging. Curr Eye Res 16:428-35
Jumblatt, M M; Willer, S S (1996) Corneal endothelial repair. Regulation of prostaglandin E2 synthesis. Invest Ophthalmol Vis Sci 37:1294-301
Jumblatt, M M (1994) Autocrine regulation of corneal endothelium by prostaglandin E2. Invest Ophthalmol Vis Sci 35:2783-90
Jumblatt, M M; Neltner, A A; Coca-Prados, M et al. (1994) EP2-receptor stimulated cyclic AMP synthesis in cultured human non-pigmented ciliary epithelium. Exp Eye Res 58:563-6