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Pigment epithelium-derived factor decreases outflow facility.

Morgan E Rogers1, Iris D Navarro, Kristin M Perkumas

  • 1Department of Ophthalmology, Duke University, Durham, North Carolina.

Investigative Ophthalmology & Visual Science
|September 14, 2013
PubMed
Summary

Pigment epithelium-derived factor (PEDF) enhances barrier function in Schlemm's canal (SC) cells and reduces aqueous humor outflow facility in mouse eyes. This suggests PEDF signaling could be a therapeutic target for managing intraocular pressure.

Keywords:
PEDFSchlemm's canalVEGFaqueous humorglaucomagrowth factorsoutflow facilitytrabecular meshwork

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Area of Science:

  • Ophthalmology
  • Cell Biology
  • Physiology

Background:

  • Pigment epithelium-derived factor (PEDF) is known to regulate blood-retinal barrier function.
  • The role of PEDF in the conventional aqueous humor outflow pathway is not well understood.
  • Schlemm's canal (SC) endothelium forms the inner wall of the conventional outflow pathway.

Purpose of the Study:

  • To investigate the effects of PEDF on the barrier function of cultured SC endothelial cells.
  • To determine the impact of PEDF on aqueous humor outflow facility in mouse eyes in situ.

Main Methods:

  • Transendothelial electrical resistance (TEER) was measured in human SC and porcine angular aqueous plexus (AAP) cells to assess barrier function.
  • Enucleated mouse eyes were perfused with varying concentrations of PEDF (0.1 and 1 μg/mL) using a computer-controlled system.
  • Outflow facility was calculated by measuring aqueous humor flow rate at different perfusion pressures.

Main Results:

  • PEDF significantly increased TEER in porcine AAP cells in a dose-dependent manner.
  • PEDF (1 μg/mL) stabilized TEER in human SC monolayers over 48 hours.
  • Perfusion with PEDF resulted in a significant decrease in outflow facility in mouse eyes, with a 43.7% reduction at 1 μg/mL and 19.9% at 100 ng/mL.

Conclusions:

  • PEDF enhances the barrier function of SC endothelial cells in both in vitro and in situ models.
  • Modulating PEDF signaling in SC cells offers potential therapeutic strategies for ocular hypertension and hypotony.
  • Targeting PEDF may help manage intraocular pressure by altering aqueous humor outflow.