Increased stiffness and flow resistance of the inner wall of Schlemm's canal in glaucomatous human eyes

Amir Vahabikashi, Ariel Gelman, Biqin Dong, Lihua Gong, Elliott D.K. Cha, Margit Schimmel, Ernst R. Tamm, Kristin Perkumas, W. Daniel Stamer, Cheng Sun, Hao F. Zhang, Haiyan Gong, Mark Johnson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

The cause of the elevated outflow resistance and consequent ocular hypertension characteristic of glaucoma is unknown. To investigate possible causes for this flow resistance, we used atomic force microscopy (AFM) with 10-μm spherical tips to probe the stiffness of the inner wall of Schlemm's canal as a function of distance from the tissue surface in normal and glaucomatous postmortem human eyes, and 1-μm spherical AFM tips to probe the region immediately below the tissue surface. To localize flow resistance, perfusion and imaging methods were used to characterize the pressure drop in the immediate vicinity of the inner wall using giant vacuoles that form in Schlemm's canal cells as micropressure sensors. Tissue stiffness increased with increasing AFM indentation depth. Tissues from glaucomatous eyes were stiffer compared with normal eyes, with greatly increased stiffness residing within ~1 μm of the inner-wall surface. Giant vacuole size and density were similar in normal and glaucomatous eyes despite lower flow rate through the latter due to their higher flow resistance. This implied that the elevated flow resistance found in the glaucomatous eyes was localized to the same region as the increased tissue stiffness. Our findings implicate pathological changes to biophysical characteristics of Schlemm's canal endothelia and/or their immediate underlying extracellular matrix as cause for ocular hypertension in glaucoma.

Original languageEnglish (US)
Pages (from-to)26555-26563
Number of pages9
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number52
DOIs
StatePublished - Dec 26 2019

Keywords

  • Biophysics
  • Extracellular matrix
  • Primary open-angle glaucoma

ASJC Scopus subject areas

  • General

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