April 2009
Volume 50, Issue 13
ARVO Annual Meeting Abstract  |   April 2009
ADAMTS Expression in Trabecular Meshwork and the Effects on Outflow Facility
Author Affiliations & Notes
  • K. E. Keller
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon
  • J. M. Bradley
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon
  • T. S. Acott
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon
  • Footnotes
    Commercial Relationships  K.E. Keller, None; J.M. Bradley, None; T.S. Acott, None.
  • Footnotes
    Support  Supported by grants from the Glaucoma Research Foundation, by NIH grants EY003279, EY008247 and EY010572 and an unrestricted grant from Research to Prevent Blindness, New York, NY.
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 4850. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      K. E. Keller, J. M. Bradley, T. S. Acott; ADAMTS Expression in Trabecular Meshwork and the Effects on Outflow Facility. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4850.

      Download citation file:

      © ARVO (1962-2015); The Authors (2016-present)

  • Supplements

Purpose: : Matrix metalloproteinases (MMPs) degrade extracellular matrix and increase outflow facility in anterior segment perfusion culture. One subclass of MMPs is the ADAMTSs (a disintegrin and metalloproteinase with thrombospondin type 1 motifs). This study examines the effects of ADAMTSs in outflow facility and investigates their mRNA and protein expression in trabecular meshwork (TM) cells and tissue.

Methods: : Human and porcine anterior segments in perfusion culture were treated with recombinant ADAMTSs-1, -4, and -5. Outflow facility was constantly monitored. ADAMTS-1, -4, and -5 mRNA expression was quantitated by qRT-PCR in human TM cells treated for 12, 24, and 48 hrs with TNF, IL-1, their combination, and in response to mechanical stretch. ADAMTS-4 mRNA expression was assessed in normal and glaucomatous human anterior segments that were perfused at physiological or increased pressure (2x) for 24 hrs. Immunofluorescence and confocal microscopy was used to determine the localization of ADAMTS-4 and -5 in human TM cells and tissue.

Results: : Porcine eyes perfused with 1 µg or 0.5 µg ADAMTS-4 increased outflow facility approximately 2.6- or 2-fold in 48 hrs, respectively. ADAMTS-1 and -5 increased outflow facility 1.3 and 1.4-fold, respectively. Human eyes perfused with 1 µg ADAMTS-4 increased 2.2-fold in 24 hrs, whereas ADAMTS-1 did not increase outflow facility. Cytokine treatments, which increase outflow facility, increased mRNA expression of ADAMTS-4 and -5, especially at 12 and 24 hrs. Mechanical stretch increased ADAMTS-4 mRNA expression but conversely decreased ADAMTS-5 expression. In normal human eyes, ADAMTS-4 mRNA expression increased 2.3-fold in response to pressure. However, glaucoma eyes did not exhibit a similar response. Immunofluorescence and confocal microscopy showed that ADAMTS-4 was expressed in the juxtacanalicular region of the TM in human anterior segments perfused at increased pressure. In human TM cells, ADAMTS-4 co-localized with cortactin in podosome-like structures (PILS), but ADAMTS-5 did not.

Conclusions: : These results show differential responses and expression of ADAMTSs -1, -4 and -5 in human TM cells. Combined, these results suggest that ADAMTS-4 is an important regulator of outflow facility.

Keywords: extracellular matrix • trabecular meshwork • outflow: trabecular meshwork 

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.