Endothelin and Its Suspected Role in the Pathogenesis and Possible Treatment of Glaucoma

Abstract

Purpose: To review the role of endothelin in intraocular pressure control, its effect on the trabecular meshwork (TM) and the outflow facility, effect on ocular blood flow and vascular regulation and the potential role of endothelin-1 (ET-1) antagonism in the therapeutic paradigm of glaucoma.

Methods: A thorough review of the medical literature and a meta-analysis on the level of ET-1 in OAG patients in an attempt to demonstrate the evolving importance of endothelin in glaucoma.

Results: ET-1 has been identified in the plasma in concentrations that are markedly increased in a number of systemic as well as ocular pathologies such as glaucoma where underlying vascular dysfunction and pathology play a role. It has been shown that ET-1 induces human TM cell contraction in culture and that it can affect the outflow facility. Evidence indicates that systemic ET-1 regulatory mechanisms and vascular responses to it are also altered in glaucoma. Recently, several endothelin antagonists have been shown to have a potential role in glaucoma therapy. In our meta-analysis, only patients with normal tension glaucoma (NTG) (as opposed to patients with high tension glaucoma (HTG)) had significantly higher plasma ET-1 levels compared to non-glaucomatous control. High tension glaucomaHTG patients had significant higher levels of ET-1 in the aqueous humor.

Conclusions: The potential role of ET-1 antagonism in the therapeutic paradigm of glaucoma is an exciting possible new approach in the treatment of OAG patients. In NTG, ET-1 may have both a local and systemic component of vascular dysregulation, while whereas in HTG, the role of ET-1 may be dominantly localized to ocular tissue.

Keywords::

• Endothelin
• Glaucoma
• Vascular dysregulation
• Ocular blood flow
• Treatment

Declaration of interest: Supported in part by an unrestricted grant from Research to Prevent Blindness. Alon Harris is a consultant for Merck, Allergan and Sucampo Pharmaceuticals, and serves as lecturer for MSD and Alcon. Barbara Wirostko is a consultant for Altheos and Merck & Co. and Pfizer.