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Crimp, Microstructure, and Biomechanics: Analyzing the Eye Using Polarized Light Microscopy

Jan, Ning-Jiun (2018) Crimp, Microstructure, and Biomechanics: Analyzing the Eye Using Polarized Light Microscopy. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Glaucoma is the second leading cause of irreversible blindness worldwide. Elevated intraocular pressure (IOP) is the main risk factor for glaucoma, though sensitivity to IOP varies widely. A leading theory states that the breadth of sensitivity is due to the biomechanical variability between eyes. According to this theory, biomechanically weak eyes suffer glaucoma at lower IOPs whereas robust eyes withstand higher IOPs without glaucomatous neural tissue damage. Therefore, in order to prevent, diagnose, and treat glaucoma, we need to have a better understanding of ocular biomechanics.

Ocular biomechanics are intimately tied to the anisotropy and nonlinearity of eye tissue. Both of these macroscale properties are largely determined by the organization of collagen, the main load-bearing component of the eye. The anisotropy is related to the mesoscale collagen structure, whereas the nonlinearity is related to the microstructural collagen fiber waviness or crimp. Although many have studied the collagen anisotropy, few studies of ocular crimp exist. Hence, the microstructural basis for eye biomechanics remains unclear, precluding a mechanistic assessment and understanding of individual sensitivity to IOP. The main goal of this project was to characterize the collagen crimp in the eye.

The lack of information on ocular crimp stems largely from the absence of a suitable imaging technique that can quantify ocular crimp with high resolution over a wide field-of-view. We established a method using polarized light microscopy (PLM) to quantify collagen fiber orientation in the eye and characterized the accuracy, repeatability, and robustness of our method. We then used PLM to characterize the crimp distribution in the eye. We also characterized how the crimp differed in eyes fixed at different IOPs and tracked how ocular crimp changed with stretch. Our studies revealed many complex aspects of collagen architecture in the eye, including the existence of fibers that are arranged radially around the optic nerve head and highly uniform crimp in the lamina cribrosa and cornea. Our findings helped elucidate the role of crimp in determining eye biomechanics and provided insight into collagen patterns that play a central role in the pathophysiology of glaucoma.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Jan, Ning-Jiunnij14@pitt.edunij140000-0001-7197-891X
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairSigal, Ian A.ian@ocularbiomechanics.comian.sigal0000-0002-0790-7911
Committee MemberLathrop, Kiralathropkl@upmc.edukll210000-0003-0686-8831
Amini, Rouzbehramini@uakron.edu0000-0003-3632-6195
Loewen, Nilsloewen.nils@gmail.comnal580000-0001-7167-1213
Geest, Jonathan Vandejpv20@pitt.edujpv200000-0003-2444-1751
Date: 25 September 2018
Date Type: Publication
Defense Date: 15 June 2018
Approval Date: 25 September 2018
Submission Date: 3 July 2018
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 206
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: Crimp, Collagen, Optic Nerve Head, Lamina Cribrosa, Peripapillary Sclera, Glaucoma, IOP, Eye
Date Deposited: 25 Sep 2018 14:10
Last Modified: 25 Sep 2019 05:15

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