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Trabecular Meshwork Response to Pressure Elevation in the Living Human Eye
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Trabecular Meshwork Response to Pressure Elevation in the Living Human Eye

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Differential effects of ADAMTS-1, -4, and -5 in the trabecular meshwork

Kate E Keller1, John M Bradley, Ted S Acott

  • 1Casey Eye Institute, Oregon Health and Science University, Portland, Oregon 97239-4197, USA.

Investigative Ophthalmology & Visual Science
|June 26, 2009
PubMed
Abstract

Insights

ADAMTS-4, a protein in the trabecular meshwork, increases aqueous humor outflow facility. This study found ADAMTS-4 expression and function differ from ADAMTS-1 and -5, suggesting its role in regulating intraocular pressure.

Area of Science:

  • Ophthalmology
  • Biochemistry
  • Extracellular Matrix Biology

Background:

  • Matrix metalloproteinases (MMPs) degrade extracellular matrix (ECM) and influence ocular outflow.
  • ADAMTSs (a disintegrin and metalloproteinase with thrombospondin type 1 motifs) are a subgroup of MMPs.
  • The role of specific ADAMTS members in regulating trabecular meshwork (TM) function and aqueous humor outflow is not fully understood.

Purpose of the Study:

  • To investigate the effects of ADAMTS-1, ADAMTS-4, and ADAMTS-5 on outflow facility.
  • To examine the mRNA levels and protein expression of ADAMTS-1, -4, and -5 in the human trabecular meshwork (TM).

Main Methods:

  • Quantification of ADAMTS mRNA in TM cells using qRT-PCR following stimulation with cytokines or mechanical stretch.
  • Assessment of ADAMTS-4 mRNA in human anterior segments under varying perfusion pressures.
  • Immunofluorescence localization of ADAMTS proteins in human TM cells and tissues.
  • Perfusion culture of anterior segments treated with recombinant ADAMTS proteins to measure outflow facility.

Main Results:

  • Cytokines increased mRNA for all three ADAMTSs; mechanical stretch differentially affected ADAMTS-4 (increased) versus ADAMTS-1 and -5 (decreased).
  • ADAMTS-4 mRNA and protein levels were elevated in response to increased pressure and in glaucomatous eyes, localizing to the juxtacanalicular region.
  • Recombinant ADAMTS-4, but not ADAMTS-1 or -5, significantly increased outflow facility in anterior segment cultures.

Conclusions:

  • ADAMTS-1, -4, and -5 exhibit distinct expression patterns and responses in human TM cells.
  • ADAMTS-4 plays a significant role in modulating trabecular meshwork outflow facility.
  • ADAMTS-4 is identified as a potential therapeutic target for managing intraocular pressure.

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