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The Mechanobiology of the Crystalline Lens

Kumar, Bharat
http://orcid.org/0000-0003-1024-0748
http://rave.ohiolink.edu/etdc/view?acc_num=osu1587649113548924

Abstract Details

2020, Doctor of Philosophy, Ohio State University, Biomedical Engineering.
The lens is a pivotal organ in the eye; playing a crucial role in the process of accommodation, by which the eye is able to alter its focal distance. The lens continuously grows in size throughout the lifetime, unlike the globe which maintains a constant size from adulthood. This growth is a result of lens epithelial cell (LEC) proliferation, which ultimately leads to an increase in the number of fiber cells. Changes in the size, stiffness, and shape of the lens contribute to the etiology of age-related refractive issues in the lens, namely presbyopia, and cataracts. Additionally understanding the forces that control the proliferation of LECs has implications in developing therapies for posterior capsule opacification (PCO) and translational research in clinical applications for lens regeneration. The processes governing the growth of the lens are therefore of great clinical interest; however, they are not fully understood. This dissertation considers the broadest context of the translational utility of understanding lens growth, beginning with the long-term goal of regenerating a lens following cataract extraction. This review is followed by the first basic science studies investigating mechanobiological regulation of lens growth. This represents a significant step towards understanding lens biology since, to date, all such studies have been conducted without consideration for the refractive state of the lens. In the first study, and for the first time, LECs were found to be mechanosensitive in vitro using a bespoke stretching device. The LEC proliferation rate was found to depend strongly on the amplitude and frequency of stretching. This dependence was effectively eliminated via chemical inhibition of yes-associated protein (YAP) activation using verteporfin. These findings suggest that zonular tension is a major driving force for lens growth. The second study investigated the localization of proliferative activity. This spatial distribution of proliferating LECs was altered significantly depending on whether static or cyclic strains were applied. Prior studies on cellular mechanisms of lens growth have used non-accommodating species (i.e. mouse), finding that adult lens growth is driven by LEC proliferation in the “germinative zone” near the equator. When lenses were not stretched or stretched to a fixed extent, proliferation was observed primarily in the equatorial region. When oscillatory stretching was performed, proliferation was more uniform across the epithelium. The strong influence of equatorial stretching therefore must be considered when considering the growth and morphogenesis of the human lens. These novel findings have a significant impact in the understanding of the lens growth and are foundational in the field of lens mechanobiology. By demonstrating that the LECs are mechanosensitive, that YAP is involved in this mechanosensation, and that location of these changes depends on the dynamic nature of the applied stretching, many new research questions are available and may be studied using the methods described herein.
Matthew Reilly, PhD (Advisor)
Cynthia Roberts, PhD (Committee Member)
Heather Chandler, PhD (Committee Member)
107 p.
Biomedical Engineering; Ophthalmology
Lens, Mechanobiology, Crystalline Lens, Ophthalmology, Presbyopia

Recommended Citations

Citations

  • Kumar, B. (2020). The Mechanobiology of the Crystalline Lens [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1587649113548924

    APA Style (7th edition)

  • Kumar, Bharat. The Mechanobiology of the Crystalline Lens. 2020. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1587649113548924.

    MLA Style (8th edition)

  • Kumar, Bharat. "The Mechanobiology of the Crystalline Lens." Doctoral dissertation, Ohio State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu1587649113548924

    Chicago Manual of Style (17th edition)

osu1587649113548924
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This open access ETD is published by The Ohio State University and OhioLINK.