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

Publication ,  Journal Article
Vahabikashi, A; Gelman, A; Dong, B; Gong, L; Cha, EDK; Schimmel, M; Tamm, ER; Perkumas, K; Stamer, WD; Sun, C; Zhang, HF; Gong, H; Johnson, M
Published in: Proc Natl Acad Sci U S A
December 26, 2019

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.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

December 26, 2019

Volume

116

Issue

52

Start / End Page

26555 / 26563

Location

United States
 

Citation

APA
Chicago
ICMJE
MLA
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Vahabikashi, A., Gelman, A., Dong, B., Gong, L., Cha, E. D. K., Schimmel, M., … Johnson, M. (2019). Increased stiffness and flow resistance of the inner wall of Schlemm's canal in glaucomatous human eyes. Proc Natl Acad Sci U S A, 116(52), 26555–26563. https://doi.org/10.1073/pnas.1911837116
Vahabikashi, Amir, Ariel Gelman, Biqin Dong, Lihua Gong, Elliott D. K. Cha, Margit Schimmel, Ernst R. Tamm, et al. “Increased stiffness and flow resistance of the inner wall of Schlemm's canal in glaucomatous human eyes.Proc Natl Acad Sci U S A 116, no. 52 (December 26, 2019): 26555–63. https://doi.org/10.1073/pnas.1911837116.
Vahabikashi A, Gelman A, Dong B, Gong L, Cha EDK, Schimmel M, et al. Increased stiffness and flow resistance of the inner wall of Schlemm's canal in glaucomatous human eyes. Proc Natl Acad Sci U S A. 2019 Dec 26;116(52):26555–63.
Vahabikashi, Amir, et al. “Increased stiffness and flow resistance of the inner wall of Schlemm's canal in glaucomatous human eyes.Proc Natl Acad Sci U S A, vol. 116, no. 52, Dec. 2019, pp. 26555–63. Pubmed, doi:10.1073/pnas.1911837116.
Vahabikashi A, Gelman A, Dong B, Gong L, Cha EDK, Schimmel M, Tamm ER, Perkumas K, Stamer WD, Sun C, Zhang HF, Gong H, Johnson M. Increased stiffness and flow resistance of the inner wall of Schlemm's canal in glaucomatous human eyes. Proc Natl Acad Sci U S A. 2019 Dec 26;116(52):26555–26563.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

December 26, 2019

Volume

116

Issue

52

Start / End Page

26555 / 26563

Location

United States