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Biomechanical strain as a trigger for pore formation in Schlemm's canal endothelial cells.

Publication ,  Journal Article
Braakman, ST; Pedrigi, RM; Read, AT; Smith, JAE; Stamer, WD; Ethier, CR; Overby, DR
Published in: Exp Eye Res
October 2014

The bulk of aqueous humor passing through the conventional outflow pathway must cross the inner wall endothelium of Schlemm's canal (SC), likely through micron-sized transendothelial pores. SC pore density is reduced in glaucoma, possibly contributing to obstructed aqueous humor outflow and elevated intraocular pressure (IOP). Little is known about the mechanisms of pore formation; however, pores are often observed near dome-like cellular outpouchings known as giant vacuoles (GVs) where significant biomechanical strain acts on SC cells. We hypothesize that biomechanical strain triggers pore formation in SC cells. To test this hypothesis, primary human SC cells were isolated from three non-glaucomatous donors (aged 34, 44 and 68), and seeded on collagen-coated elastic membranes held within a membrane stretching device. Membranes were then exposed to 0%, 10% or 20% equibiaxial strain, and the cells were aldehyde-fixed 5 min after the onset of strain. Each membrane contained 3-4 separate monolayers of SC cells as replicates (N = 34 total monolayers), and pores were assessed by scanning electron microscopy in 12 randomly selected regions (∼65,000 μm(2) per monolayer). Pores were identified and counted by four independent masked observers. Pore density increased with strain in all three cell lines (p < 0.010), increasing from 87 ± 36 pores/mm(2) at 0% strain to 342 ± 71 at 10% strain; two of the three cell lines showed no additional increase in pore density beyond 10% strain. Transcellular "I-pores" and paracellular "B-pores" both increased with strain (p < 0.038), however B-pores represented the majority (76%) of pores. Pore diameter, in contrast, appeared unaffected by strain (p = 0.25), having a mean diameter of 0.40 μm for I-pores (N = 79 pores) and 0.67 μm for B-pores (N = 350 pores). Pore formation appears to be a mechanosensitive process that is triggered by biomechanical strain, suggesting that SC cells have the ability to modulate local pore density and filtration characteristics of the inner wall endothelium based on local biomechanical cues. The molecular mechanisms of pore formation and how they become altered in glaucoma may be studied in vitro using stretched SC cells.

Duke Scholars

Published In

Exp Eye Res

DOI

EISSN

1096-0007

Publication Date

October 2014

Volume

127

Start / End Page

224 / 235

Location

England

Related Subject Headings

  • Vacuoles
  • Tissue Donors
  • Stress, Mechanical
  • Sclera
  • Porosity
  • Ophthalmology & Optometry
  • Microscopy, Electron, Scanning
  • Limbus Corneae
  • Intracellular Space
  • Humans
 

Citation

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Braakman, S. T., Pedrigi, R. M., Read, A. T., Smith, J. A. E., Stamer, W. D., Ethier, C. R., & Overby, D. R. (2014). Biomechanical strain as a trigger for pore formation in Schlemm's canal endothelial cells. Exp Eye Res, 127, 224–235. https://doi.org/10.1016/j.exer.2014.08.003
Braakman, Sietse T., Ryan M. Pedrigi, A Thomas Read, James A. E. Smith, W Daniel Stamer, C Ross Ethier, and Darryl R. Overby. “Biomechanical strain as a trigger for pore formation in Schlemm's canal endothelial cells.Exp Eye Res 127 (October 2014): 224–35. https://doi.org/10.1016/j.exer.2014.08.003.
Braakman ST, Pedrigi RM, Read AT, Smith JAE, Stamer WD, Ethier CR, et al. Biomechanical strain as a trigger for pore formation in Schlemm's canal endothelial cells. Exp Eye Res. 2014 Oct;127:224–35.
Braakman, Sietse T., et al. “Biomechanical strain as a trigger for pore formation in Schlemm's canal endothelial cells.Exp Eye Res, vol. 127, Oct. 2014, pp. 224–35. Pubmed, doi:10.1016/j.exer.2014.08.003.
Braakman ST, Pedrigi RM, Read AT, Smith JAE, Stamer WD, Ethier CR, Overby DR. Biomechanical strain as a trigger for pore formation in Schlemm's canal endothelial cells. Exp Eye Res. 2014 Oct;127:224–235.
Journal cover image

Published In

Exp Eye Res

DOI

EISSN

1096-0007

Publication Date

October 2014

Volume

127

Start / End Page

224 / 235

Location

England

Related Subject Headings

  • Vacuoles
  • Tissue Donors
  • Stress, Mechanical
  • Sclera
  • Porosity
  • Ophthalmology & Optometry
  • Microscopy, Electron, Scanning
  • Limbus Corneae
  • Intracellular Space
  • Humans