The trabecular meshwork of the eye is the principal site of outflow resistance to the aqueous humor. We are looking at the effects of prostaglandin derivatives, latanoprost acid and prostamide, on the trabecular meshwork. These compounds, which are very similar in structure, cause reductions in intraocular pressure and are medications currently used for glaucoma treatment. It is thought that latanoprost acid works on the uvealscleral outflow pathway but not on the trabecular meshwork. The prostamide is reported to work on both outflow pathways. The exact mechanisms by which these compounds work are not known and the long-term effects on the anterior segment of the eye are unclear. Gene array technology has been used to investigate the changes that these two drugs cause within the trabecular meshwork and the ciliary muscle. The effects of the two drugs are different in the cells from the two tissues. In both cell types, however, the expressions of two genes are changed in ways which would increase facility. Verification of the gene arrays is being done. Our long-term goal is to develop a selective gene transfer system to assist cells in the outflow pathway reduce the resistance to aqueous humor outflow and thereby stop visual field loss. Two components from the trabecular meshwork that might be important in regulating outflow both in normal and in diseased conditions have been identified and studied. These proteins are migration inhibitory factor, MIF, and SPARC. These proteins influence extracellular matrix turnover. We believe overexpression of some of these proteins might be beneficial in the trabecular meshwork to reduce intraocular pressure.We are studying the effects of the expression of these two proteins on human trabecular meshwork cells and ciliary muscle cells. These candidates should be useful in gene therapy of glaucoma.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Intramural Research (Z01)
Project #
1Z01EY000303-08
Application #
6672755
Study Section
(LMOD)
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2002
Total Cost
Indirect Cost
Name
U.S. National Eye Institute
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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