Endothelin: Is It a Contributor to Glaucoma Pathophysiology?

Abstract

Endothelin is a vasoactive peptide that has been shown to play an important role in vascular homeostasis. Recently, endothelin and its receptors have been found in ocular tissues where it appears to have a regulatory function. Endothelin is found in both the aqueous and vitreous humors and its concentration is elevated in glaucoma patients and in animal models of glaucoma. In the current review, the authors present information about the distribution of endothelin and endothelin receptors in the eye and the ocular actions of endothelins. Specifically, endothelin/aqueous humor dynamics, endothelin/nitric oxide interactions, endothelin and ischemia, and endothelin/optic nerve head effects. Observations concerning the potential role of endothelin in glaucoma pathophysiology is presented and discussed relative to its effects on the optic nerve head and in relation to glaucoma theories.

PAX6 Expression and Retinal Cell Death in a Transgenic Mouse Model for Acute Angle-Closure Glaucoma

“…37 Activation of proinflammatory IL-1b might be involved in the etiology of glaucoma 35,38,39 and increased endothelin-2 expression occurs in human glaucoma during glial activation. 40 Late down-regulation of the caspase inhibitor XIAP and of Bcl-X L and Bcl-2 was observed in CLR SMaA mice on p82, similar to observations in degenerating retinas. [41][42][43] As transgenic expression of XIAP was shown to increase survival of cells in the inner retina in mouse models of ischemia, 44 it seems likely that the reduced expression of this inhibitor of apoptosis contributes to the retinal pathology and the observed loss of neuronal cells.…”

A virtual-system coupled multicanonical molecular dynamics simulation: Principles and applications to free-energy landscape of protein–protein interaction with an all-atom model in explicit solvent

“…ET1, which is a potent and long-lasting vasoconstrictor on smooth muscles of a vessel, [28][29][30][31] is thought to be an important drug target because it is related to many human diseases. [32][33][34][35][36] Because of its two intra-peptide disulfide bonds, ET1 has a compact tertiary structure in solution. In both the NMR [37][38][39] and X-ray 40 structures, the N-terminal region of ET1 adopts a somewhat distorted strand and the middle region forms a helix.…”

Optic Nerve Head Blood Flow in Glaucoma

“…Several reports have suggested a larger diurnal fluctuation of parameters for ocular blood flow including ONH blood flow in patients with POAG or NTG (Claridge & Smith, 1994;Chung et al, 1999;Okuno T et al, 2004;Pemp et al, 2009). There has also been some evidence that endothelin (ET)-1 and nitric oxide may play roles in the dysregulation of ocular blood flow in glaucoma (Yorio et al, 2002;Flammer et al, 2007;Polak et al, 2007;Nicolela, 2008;Venkataraman et al, 2010). There have been some studies on the effects of anti-glaucoma medication on ONH blood flow.…”