Endothelin1 and Nitric Oxide Synthase: Role in Glaucoma

Project Summary

Endothelin-1 (ET-1) is a small peptide molecule that causes blood vessels to constrict. It is elevated in the aqueous humor of people with primary open angle glaucoma and in the blood plasma of people with normal tension glaucoma. Chronic low-dose administration of the peptide to primates produces optic nerve damage that mirrors the damage found in glaucoma. ET-1 may also regulate another vessel-constricting molecule called nitric oxide (NO). The excess production of NO, through enzymes called NO synthases (NOS), in ocular cells also causes optic nerve damage. It has been found that in rats with glaucoma, inhibitors of the NOS-2 enzyme prevent damage to the retinal ganglion cells. In earlier research, Dr. Prasanna found evidence that ET-1 increases the amount of NOS-2 in human pigmented ciliary epithelial cells, and is now utilizing the rat model of glaucoma to examine the role of ET-1 in regulating NOS-2 gene expression. The knowledge gained from this study could help provide a basis for the use of molecules that inhibit the activity of ET-1 as a possible treatment of glaucoma.