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Full text release has been delayed at the author's request until November 07, 2027

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Towards the induction of lens regeneration: Lessons learned from newts

Tsissios, Georgios Dimitrios
http://orcid.org/0000-0002-5219-616X
http://rave.ohiolink.edu/etdc/view?acc_num=miami1668254165740229

Abstract Details

2022, Doctor of Philosophy, Miami University, Cell, Molecular and Structural Biology (CMSB).
Lens regeneration in newts is a unique and astounding biological phenomenon that has fascinated scientists for centuries. During this process, the terminally differentiated iris pigmented epithelial cells (iPECs) of the dorsal iris, lose their differentiation status, and convert into an entirely new cell type to regenerate the missing lens. Interestingly, even though the iris epithelium is a homogenous tissue, only cells from the dorsal iris possess the capacity to regenerate a lens. The ventral iris pigmented epithelial cells never participate in this process. Therefore, this system presents a unique opportunity to compare regenerating competent and incompetent tissues at the cellular and molecular levels. This dissertation consists of four individual studies with a common goal of delineating the mechanisms that drive lens regeneration. In the first study (Chapter 2) we established and validated optical coherence tomography as a powerful tool to study lens regeneration. In the second study (Chapter 3), we evaluated the effects of aging on the lens regeneration process. We characterized in detailed the kinetics of lens regeneration in three different age groups. We found that young animals regenerated much faster than older ones and suggested that this phenomenon is due to delays in cell cycle re-entry and ECM remodeling. In the third study (Chapter 4), we investigated the role of macrophages during different stages of the newt lens regeneration process. We identified that macrophages play an important role to promote iPECs cell cycle re-entry, resolve inflammation, prevent fibrosis, and remodel extracellular matrix (ECM). Furthermore, we showed that exogenous addition of FGF2 or reintroduction of an injury can rescue regeneration in macrophage depleted eyes. This paper is finalized and will be submitted for publication soon. In the fourth and last study (Chapter 5), we explored the role of Ephrin:Eph pathway signaling during lens regeneration. Remarkably, we found that blocking the phosphorylation of EphA 4 and 5 receptors, caused an induction of regeneration from the ventral iris both in vivo and in ex vivo explant cultures. This is the first report that shows an in vivo induction of lens regeneration from the, previously thought incompetent, ventral iris by inhibition of a single pathway. Overall, this dissertation provides a detailed and comprehensive description of different processes that occur during lens regeneration. Novel findings are presented in all three papers. In addition, we developed and validated new tools that have already enhanced our understanding of lens regeneration.
Katia Del Rio-Tsonis, Dr. (Advisor)
194 p.
Biology
Regeneration, lens, newts

Recommended Citations

Citations

  • Tsissios, G. D. (2022). Towards the induction of lens regeneration: Lessons learned from newts [Doctoral dissertation, Miami University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=miami1668254165740229

    APA Style (7th edition)

  • Tsissios, Georgios. Towards the induction of lens regeneration: Lessons learned from newts. 2022. Miami University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=miami1668254165740229.

    MLA Style (8th edition)

  • Tsissios, Georgios. "Towards the induction of lens regeneration: Lessons learned from newts." Doctoral dissertation, Miami University, 2022. http://rave.ohiolink.edu/etdc/view?acc_num=miami1668254165740229

    Chicago Manual of Style (17th edition)

miami1668254165740229
© 2022, some rights reserved.Creative Commons License Towards the induction of lens regeneration: Lessons learned from newts by Georgios Dimitrios Tsissios is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by Miami University and OhioLINK.