Current understanding of conventional outflow dysfunction in glaucoma

W. Daniel Stamer, Ted Acott

Research output: Contribution to journalArticle

117 Citations (Scopus)

Abstract

PURPOSE OF REVIEW: Regulation of intraocular pressure by the conventional (trabecular) outflow pathway is complicated, involving a myriad of mechanical and chemical signals. In most, intraocular pressure is maintained within a tight range over a lifetime. Unfortunately in some, dysfunction results in ocular hypertension and open-angle glaucoma. In the context of established knowledge, this review summarizes recent investigations of conventional outflow function, with the goal of identifying areas for future inquiry and therapeutic targeting. RECENT FINDINGS: Mechanical stimulation of conventional outflow cells due to intraocular pressure fluctuations impacts contractility, gene expression, pore formation, enzyme activity, and signaling. Numerous local signaling mediators in the conventional pathway such as bioactive lipids, cytokines, nitric oxide, and nucleotides participate in the regulation of outflow. Interestingly outflow through the conventional pathway is not uniform, but segmental, with passageways constantly changing due to focal protease activity of trabecular cells clearing extracellular matrix materials. The relationship between extracellular matrix expression and trabecular meshwork contractility appears to coordinately impact outflow resistance and is the target of a new class of drugs, the Rho kinase inhibitors. SUMMARY: The conventional outflow pathway is a dynamic, pressure-sensitive tissue that is vulnerable to pathology on many fronts, each representing a therapeutic opportunity.

Original languageEnglish (US)
Pages (from-to)135-143
Number of pages9
JournalCurrent Opinion in Ophthalmology
Volume23
Issue number2
DOIs
StatePublished - Mar 2012

Fingerprint

Intraocular Pressure
Glaucoma
Extracellular Matrix
Trabecular Meshwork
rho-Associated Kinases
Ocular Hypertension
Open Angle Glaucoma
Nitric Oxide
Peptide Hydrolases
Nucleotides
Pathology
Cytokines
Lipids
Gene Expression
Pressure
Enzymes
Therapeutics
Pharmaceutical Preparations

Keywords

  • Intraocular pressure
  • Outflow facility
  • Schlemm's canal
  • Trabecular meshwork

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Current understanding of conventional outflow dysfunction in glaucoma. / Stamer, W. Daniel; Acott, Ted.

In: Current Opinion in Ophthalmology, Vol. 23, No. 2, 03.2012, p. 135-143.

Research output: Contribution to journalArticle

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