Activation of a tissue-specific stress response in the aqueous outflow pathway of the eye defines the glaucoma disease phenotype

The glaucomas are a group of optic neuropathies comprising the leading caus e of irreversible blindness worldwide. Elevated intraocular pressure due to a reduction in normal aqueous outflow is a major causal risk factor. We fo und that endothelial leukocyte adhesion molecule-1 (ELAM-1), the earliest m arker for the atherosclerotic plaque in the vasculature, was consistently p resent on trabecular meshwork (TM) cells in the outflow pathways of eyes wi th glaucomas of diverse etiology. We determined expression of ELAM-1 to be controlled by activation of an interleukin-1 (IL-1) autocrine feedback loop through transcription factor NF-kappaB, and activity of this signaling pat hway was shown to protect TM cells against oxidative stress. These findings characterize a protective stress response specific to the eye's aqueous ou tflow pathways and provide the first known diagnostic indicator of glaucoma tous TM cells. They further indicate that common mechanisms contribute to t he pathophysiology of the glaucomas and vascular diseases.