The role of endothelin in the pathophysiology of glaucoma

Importance of the field: Glaucoma is the second leading cause of blindness worldwide. To date, treatment of glaucoma has focused on lowering intraocular pressure (IOP) though there are other mechanisms that might damage the optic nerve, leading to characteristic visual field loss. Endothelin, a potent vasoconstrictor, is believed to play a role in the pathogenesis of glaucomatous optic neuropathy. Areas covered in this review: We review the evidence from the last 20 years exploring the action of endothelin in the eye, its association with the pathophysiology of glaucoma, as well as the potential therapeutic role of targeting the endothelin pathway to affect disease progression in glaucomatous eyes. What the reader will gain: The goal of this paper is to inform readers about endothelin structure, actions, and role in ocular pathology, pharmacology, and potential areas of future research. Take home message: Overall, we believe that the body of evidence supports the following conclusions; i) endothelin is a potent vasoconstrictor that plays a role in ocular physiology, ii) endothelin may play a role in the pathophysiology of glaucoma and iii) modulation of the endothelin system with newly discovered potent antagonists holds promise in treating glaucoma through both pressure-dependent and pressure-independent pathways.