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Optical Techniques for Visualization and Modification of Ocular Biomechanics

Lee, Po-Yi (2023) Optical Techniques for Visualization and Modification of Ocular Biomechanics. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Glaucoma is the second leading cause of blindness worldwide. Glaucomatous vision loss starts with damage to the retinal ganglion cell axons, which exit the globe through the lamina cribrosa (LC), a structure within the optic nerve head (ONH) in the posterior pole of the eye. The causes for the axonal damage at the LC are still unclear, although much evidence points to mechanical insult as a primary damage trigger. Determining how the LC resists mechanical insult remains a major challenge, largely due to the lack of imaging techniques capable of visualizing the LC with high-resolution, wide field-of-view and high-speed, and the associated experimental techniques that allow evaluating LC biomechanics and the effects of load. Hence, this project aimed to develop novel approaches for imaging and experimental testing to enable a better understanding of the ONH architecture and biomechanics.
This dissertation encompasses three parts: leveraging improved polarized light imaging methods to characterize ONH collagen architecture and biomechanics, developing techniques to modify the mechanical properties of ONH collagen, and visualizing and analyzing the ONH vasculature. Firstly, polarized light imaging techniques were developed to visualize and quantify collagen microstructure and orientation in real-time, without labeling or stains. These techniques were integrated with a customized micro-stretcher to characterize the deformations and nonlinear mechanical behavior of the ONH. Secondly, femtosecond laser techniques were introduced to modify the mechanical properties of the LC with micrometer precision, without the need for photosensitizers. By varying the laser parameters, it is possible to induce collagen crosslinking to stiffen tissues or collagen degradation to soften tissues. Lastly, to understand LC blood perfusion, and avoid damaging LC vessels within the LC beams when using laser-induced treatments, a workflow was demonstrated to reconstruct 3D vascular networks of ONH from a monkey’s eye and analyze the geometrical parameters.
In summary, this dissertation presents the successful development of two novel polarized light microscopy techniques for ONH characterization, near-infrared femtosecond laser irradiation for collagen modification, and a workflow for reconstructing and analyzing the ONH vasculature. These advances in imaging and experimental testing represent promising approaches for further research on ocular biomechanics and glaucoma.

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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Lee, Po-Yi
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairSigal, Ian A.ian@ocularbiomechanics.comian.sigal
Committee CoChairAmini, Rouzbehr.amini@northeastern.edu
Committee MemberDavidson, Lancelad43@pitt.edulad43
Committee MemberKim, Kangkangkim@upmc.edukangkim
Committee MemberYang, Binyangb1@duq.edu
Date: 28 September 2023
Date Type: Publication
Defense Date: 30 May 2023
Approval Date: 28 September 2023
Submission Date: 31 May 2023
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 227
Institution: University of Pittsburgh
Schools and Programs: Swanson School of Engineering > Bioengineering
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: polarized light, collagen, biomechanics, optical microscopy, glaucoma, optic nerve head
Date Deposited: 14 Feb 2025 15:56
Last Modified: 14 Feb 2025 15:56
URI: http://d-scholarship.pitt.edu/id/eprint/45131

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  • Optical Techniques for Visualization and Modification of Ocular Biomechanics. (deposited 14 Feb 2025 15:56) [Currently Displayed]

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