Sphingosine-1-phosphate effects on the inner wall of Schlemm's canal and outflow facility in perfused human eyes

W. Daniel Stamer, A. Thomas Read, Grant M. Sumida, C. Ross Ethier

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Previous work has shown that sphingosine 1-phosphate (S1P) decreases outflow facility in perfused porcine eyes while dramatically increasing giant vacuole density in the inner wall of the aqueous plexus, with no obvious changes in the trabecular meshwork (TM). Due to known effects of S1P on cell-cell junction assembly in vascular endothelia, we hypothesized that S1P would decrease outflow facility in human eyes by increasing the complexity of cell-cell junctions in Schlemm's canal (SC) inner wall endothelia. Perfusion of enucleated post mortem human eyes at 8 mmHg constant pressure in the presence or absence of 5 μM S1P showed that S1P decreased outflow facility by 36 ± 20% (n = 10 pairs; p = 0.0004); an effect likely mediated by activation of S1P1 and/or S1P3 receptor subtypes, which were found to be the principal S1P receptors expressed by both TM and SC cells by RT-PCR, confocal immunofluorescence microscopy and western blot analyses. Examination of SC's inner wall using confocal microscopy revealed no consistent differences in VE-cadherin, β-catenin, phosphotyrosine or filamentous actin abundance/distribution between S1P-treated eyes and controls. Moreover, morphological inspection of conventional outflow tissues by light and scanning electron microscopy showed no significant differences between S1P-treated and control eyes, particularly in giant vacuole density. Thus, unlike the situation in porcine eyes, we did not observe changes in inner wall morphology in human eyes treated with S1P, despite a significant and immediate decrease in outflow facility in both species. Regardless, S1P receptor antagonists represent novel therapeutic prospects for ocular hypertension in humans.

Original languageEnglish (US)
Pages (from-to)980-988
Number of pages9
JournalExperimental eye research
Volume89
Issue number6
DOIs
StatePublished - Dec 2009
Externally publishedYes

Keywords

  • aqueous humor
  • cadherin
  • glaucoma
  • intraocular pressure
  • lysophospholipid
  • trabecular meshwork

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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