The vital role for nitric oxide in intraocular pressure homeostasis.

Journal Article (Journal Article;Review)

Catalyzed by endothelial nitric oxide (NO) synthase (eNOS) activity, NO is a gaseous signaling molecule maintaining endothelial and cardiovascular homeostasis. Principally, NO regulates the contractility of vascular smooth muscle cells and permeability of endothelial cells in response to either biochemical or biomechanical cues. In the conventional outflow pathway of the eye, the smooth muscle-like trabecular meshwork (TM) cells and Schlemm's canal (SC) endothelium control aqueous humor outflow resistance, and therefore intraocular pressure (IOP). The mechanisms by which outflow resistance is regulated are complicated, but NO appears to be a key player as enhancement or inhibition of NO signaling dramatically affects outflow function; and polymorphisms in NOS3, the gene that encodes eNOS modifies the relation between various environmental exposures and glaucoma. Based upon a comprehensive review of past foundational studies, we present a model whereby NO controls a feedback signaling loop in the conventional outflow pathway that is sensitive to changes in IOP and its oscillations. Thus, upon IOP elevation, the outflow pathway tissues distend, and the SC lumen narrows resulting in increased SC endothelial shear stress and stretch. In response, SC cells upregulate the production of NO, relaxing neighboring TM cells and increasing permeability of SC's inner wall. These IOP-dependent changes in the outflow pathway tissues reduce the resistance to aqueous humor drainage and lower IOP, which, in turn, diminishes the biomechanical signaling on SC. Similar to cardiovascular pathogenesis, dysregulation of the eNOS/NO system leads to dysfunctional outflow regulation and ocular hypertension, eventually resulting in primary open-angle glaucoma.

Full Text

Duke Authors

Cited Authors

  • Reina-Torres, E; De Ieso, ML; Pasquale, LR; Madekurozwa, M; van Batenburg-Sherwood, J; Overby, DR; Stamer, WD

Published Date

  • July 2021

Published In

Volume / Issue

  • 83 /

Start / End Page

  • 100922 -

PubMed ID

  • 33253900

Pubmed Central ID

  • PMC8160027

Electronic International Standard Serial Number (EISSN)

  • 1873-1635

Digital Object Identifier (DOI)

  • 10.1016/j.preteyeres.2020.100922


  • eng

Conference Location

  • England