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 language | English (US) |
|---|---|
| Pages (from-to) | 26555-26563 |
| Number of pages | 9 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 116 |
| Issue number | 52 |
| DOIs | |
| State | Published - Dec 26 2019 |
Funding
We thank Dr. Thomas Read, then in the laboratory of Dr. John Flanagan at Toronto Western Hospital and now at Georgia Tech, who taught one of us (A.V.) the extraction procedure for removal of the inner wall of Schlemm's canal. We also gratefully acknowledge helpful conversations with Prof. Ross Ethier at Georgia Tech, and support from NIH EY019696 and EY022634 and The Massachusetts Lions Eye Research Fund. ACKNOWLEDGMENTS. We thank Dr. Thomas Read, then in the laboratory of Dr. John Flanagan at Toronto Western Hospital and now at Georgia Tech, who taught one of us (A.V.) the extraction procedure for removal of the inner wall of Schlemm’s canal. We also gratefully acknowledge helpful conversations with Prof. Ross Ethier at Georgia Tech, and support from NIH EY019696 and EY022634 and The Massachusetts Lions Eye Research Fund.
Keywords
- Biophysics
- Extracellular matrix
- Primary open-angle glaucoma
ASJC Scopus subject areas
- General