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Pigment epithelium-derived factor decreases outflow facility.

Publication ,  Journal Article
Rogers, ME; Navarro, ID; Perkumas, KM; Niere, SM; Allingham, RR; Crosson, CE; Stamer, WD
Published in: Invest Ophthalmol Vis Sci
October 11, 2013

PURPOSE: Pigment epithelium-derived factor (PEDF) regulates blood-retinal barrier function. As a constituent of aqueous humor, the role of PEDF in conventional outflow function is unknown. The goals of the study were to examine the effects of PEDF on barrier function of cultured Schlemm's canal (SC) endothelia and outflow facility in mouse eyes in situ. METHODS: To model the inner wall of SC, transendothelial electrical resistance (TEER) of human SC and porcine angular aqueous plexus (AAP) cells was monitored. To examine an intact conventional outflow pathway, enucleated eyes from culled C57BL/6 mice were perfused with PEDF using a computer-controlled system. Purified PEDF (0.1 and 1 μg/mL) was perfused at four different pressure steps (4, 8, 15, 20 mm Hg), measuring flow to determine outflow facility (slope of flow/pressure relationship). RESULTS: Pigment epithelium-derived factor increased TEER of porcine AAP cells in a dose-dependent fashion (0.3-3 μg/mL), and 1 μg/mL recombinant PEDF or conditioned media from pigmented retinal pigment epithelial monolayers stabilized TEER of human SC monolayers over time (0-48 hours). In perfusion experiments, we observed a 43.7% decrease in outflow facility (0.016 vs. 0.029 μL/min/mm Hg, P = 4.5 × 10⁻⁵) in eyes treated with 1 μg/mL PEDF compared to vehicle-perfused controls, and a 19.9% decrease (0.021 vs. 0.027 μL/min/mm Hg, P = 0.003) at 100 ng/mL PEDF. CONCLUSIONS: Pigment epithelium-derived factor increased barrier function in both the in vitro and in situ models of the inner wall of SC. Modification of PEDF signaling in SC cells may be therapeutically exploited to increase outflow facility in people with ocular hypertension or decrease outflow facility in those with hypotony.

Duke Scholars

Published In

Invest Ophthalmol Vis Sci

DOI

EISSN

1552-5783

Publication Date

October 11, 2013

Volume

54

Issue

10

Start / End Page

6655 / 6661

Location

United States

Related Subject Headings

  • Trabecular Meshwork
  • Swine
  • Serpins
  • Ophthalmology & Optometry
  • Nerve Growth Factors
  • Microscopy, Electron, Scanning
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Rogers, M. E., Navarro, I. D., Perkumas, K. M., Niere, S. M., Allingham, R. R., Crosson, C. E., & Stamer, W. D. (2013). Pigment epithelium-derived factor decreases outflow facility. Invest Ophthalmol Vis Sci, 54(10), 6655–6661. https://doi.org/10.1167/iovs.13-12766
Rogers, Morgan E., Iris D. Navarro, Kristin M. Perkumas, Shannon M. Niere, R Rand Allingham, Craig E. Crosson, and W Daniel Stamer. “Pigment epithelium-derived factor decreases outflow facility.Invest Ophthalmol Vis Sci 54, no. 10 (October 11, 2013): 6655–61. https://doi.org/10.1167/iovs.13-12766.
Rogers ME, Navarro ID, Perkumas KM, Niere SM, Allingham RR, Crosson CE, et al. Pigment epithelium-derived factor decreases outflow facility. Invest Ophthalmol Vis Sci. 2013 Oct 11;54(10):6655–61.
Rogers, Morgan E., et al. “Pigment epithelium-derived factor decreases outflow facility.Invest Ophthalmol Vis Sci, vol. 54, no. 10, Oct. 2013, pp. 6655–61. Pubmed, doi:10.1167/iovs.13-12766.
Rogers ME, Navarro ID, Perkumas KM, Niere SM, Allingham RR, Crosson CE, Stamer WD. Pigment epithelium-derived factor decreases outflow facility. Invest Ophthalmol Vis Sci. 2013 Oct 11;54(10):6655–6661.

Published In

Invest Ophthalmol Vis Sci

DOI

EISSN

1552-5783

Publication Date

October 11, 2013

Volume

54

Issue

10

Start / End Page

6655 / 6661

Location

United States

Related Subject Headings

  • Trabecular Meshwork
  • Swine
  • Serpins
  • Ophthalmology & Optometry
  • Nerve Growth Factors
  • Microscopy, Electron, Scanning
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Humans