
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.09.05.609208
preprint
1
Article
Impact of elevated IOP on lamina cribrosa oxygenation; A combined experimental-computational study on monkeys
Lu Yuankai
Hua Yi
Wang Bingrui
Zhong Fuqiang
Theophanous Andrew
Tahir Shaharoz
Lee Po-Yi
Sigal Ian A. http://orcid.org/0000-0002-0790-7911

10 9 2024
2024.09.05.609208https://creativecommons.org/licenses/by-nc/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.09.05.609208
nihpp-2024.09.05.609208.pdf
Purpose

Our goal is to evaluate how lamina cribrosa (LC) oxygenation is affected by the tissue distortions resulting from elevated IOP.

Design

Experimental study on monkeys

Subjects

Four healthy monkey eyes with OCT scans with IOP of 10 to 50 mmHg, and then with histological sections of LC.

Methods

Since in-vivo LC oxygenation measurement is not yet possible, we used 3D eye-specific numerical models of the LC vasculature which we subjected to experimentally-derived tissue deformations. We reconstructed 3D models of the LC vessel networks of 4 healthy monkey eyes from histological sections. We also obtained in-vivo IOP-induced tissue deformations from a healthy monkey using OCT images and digital volume correlation analysis techniques. The extent that LC vessels distort under a given OCT-derived tissue strain remains unknown. We therefore evaluated two biomechanics-based mapping techniques: cross-sectional and isotropic. The hemodynamics and oxygenations of the four vessel networks were simulated for deformations at several IOPs up to 60mmHg. The results were used to determine the effects of IOP on LC oxygen supply, assorting the extent of tissue mild and severe hypoxia.

Main Outcome Measures

IOP-induced deformation, vasculature structure, blood supply, and oxygen supply for LC region

Result

IOP-induced deformations reduced LC oxygenation significantly. More than 20% of LC tissue suffered from mild hypoxia when IOP reached 30 mmHg. Extreme IOP(>50mmHg) led to large severe hypoxia regions (>30%) in the isotropic mapping cases.

Conclusion

Our models predicted that moderately elevated IOP can lead to mild hypoxia in a substantial part of the LC, which, if sustained chronically, may contribute to neural tissue damage. For extreme IOP elevations, severe hypoxia was predicted, which would potentially cause more immediate damage. Our findings suggest that despite the remarkable LC vascular robustness, IOP-induced distortions can potentially contribute to glaucomatous neuropathy.
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