April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Dexamethasone Administration Decreases SPARC Expression in Human Trabecular Meshwork and Increases IOP in SPARC-null Mice
Author Affiliations & Notes
  • Ramez I. Haddadin
    Ophthalmology - Glaucoma Service, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts
  • Dong-Jin Oh
    Ophthalmology - Glaucoma Service, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts
  • E. H. Sage
    Benaroya Research Institute at Virginia Mason, Seattle, Washington
  • Douglas J. Rhee
    Ophthalmology - Glaucoma Service, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  Ramez I. Haddadin, None; Dong-Jin Oh, None; E. H. Sage, None; Douglas J. Rhee, None
  • Footnotes
    Support  NIH Grant EY019654, NIH Grant EY014104, Massachusetts Lions Eye Research
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 5920. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Ramez I. Haddadin, Dong-Jin Oh, E. H. Sage, Douglas J. Rhee; Dexamethasone Administration Decreases SPARC Expression in Human Trabecular Meshwork and Increases IOP in SPARC-null Mice. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5920.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: : SPARC is a matricellular protein associated with profibrotic states that is located within a known primary open-angle glaucoma (POAG) locus, 5q22.1-q32 (GLC1M). SPARC-null mice exhibit a 15-20% lower intraocular pressure (IOP). Steroid-induced glaucoma and POAG both result from increased outflow resistance. SPARC may be part of the pathophysiology of steroid-induced glaucoma as well. We studied the effect of dexamethasone (DEX) on the IOP of SPARC-null (KO) and wild-type (WT) mice as well as on SPARC protein and mRNA levels in vitro.

Methods: : Five to six week-old WT and KO mice were fed ad lib and given drinking water containing 10 mg/L of dexamethasone sodium phosphate. IOPs were measured with the TonoLab tonometer prior to starting treatment, weekly during treatment, and 4 days after stopping treatment. We also incubated trabecular meshwork (TM) and ciliary body smooth muscle (CBSM) cells with DEX for 1, 3, and 7 days. Expression of SPARC mRNA, cell/extracellular matrix (ECM)-bound protein, and soluble protein secreted into the culture media were measured by real-time RT-PCR, western blotting, and ELISA, respectively.

Results: : Average IOP measurements of WT mice treated with DEX and control were 21.3, 22.4, 24.5, 19.7, 20.7, 19.5 mm Hg; and 21.2, 20.5, 22.7, 19.6, 19.4, 18.9 mm Hg at 0, 1, 2, 3, 4, and 4.5 weeks, respectively (n=22, 20; p>0.05 at all time points). Average IOP measurements of SPARC-null mice treated with DEX and control were 17.7, 19.6, 20.8, 20.5, 19.2, 18.5 mm Hg; and 16.9, 16.4, 17.8, 17.9, 16.9, 17.9 mm Hg at 0, 1, 2, 3, 4, and 4.5 weeks, respectively (n=20, 18; p<0.05 at 1, 2, 3 and 4 weeks). KO mice exhibited proportionally greater peak elevations in IOP at 1 week (19.2% versus 9.7%). Compared to control-treated TM cells, cells incubated with DEX showed a significant decrease in SPARC mRNA levels at 3- and 7-days, by 0.323- and 0.372-fold, respectively (p <0.05). Cell/ECM-bound SPARC protein in TM cells was decreased at 1-, 3-, and 7-days, by 30.8, 20.1, and 17.6% (p <0.05). Soluble, secreted SPARC protein was unchanged at all time points. CBSM cells exhibited no significant changes in SPARC mRNA, or protein levels.

Conclusions: : Administration of DEX resulted in statistically significant IOP elevations in SPARC-null mice but not in WT mice. Incubation with DEX lowered cell/ECM-bound SPARC protein and mRNA levels in TM but not CBSM cells. SPARC may play a counter-regulatory role in steroid-induced glaucoma.

Keywords: intraocular pressure • trabecular meshwork • corticosteroids 
×
×

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.

×