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Access Type
WSU Access
Date of Award
January 2025
Degree Type
Dissertation
Degree Name
Ph.D.
Department
Anatomy and Cell Biology
First Advisor
Ryan Thummel
Abstract
Humans have been fascinated by vision science and understanding how we perceive the world differently for centuries, with some of the earliest reports of inherited visual deficits in humans dating back to the 1700’s. Since that time, the exponential advancement of scientific knowledge has led us to a deep understanding of the molecular and cellular functionality of the visual system, from invertebrates to humans and everything in-between. One organism that has become the subject of intense research over the past two decades for its remarkable ability to regenerate its retina is the zebrafish. In response to acute damage in the zebrafish retina, a resident macroglia cell conserved in all vertebrate retinas, Müller glia, undergo a de-differentiation event and are capable of producing progenitor cells that will repopulate the entire adult retina. Müller glia have been studied in several contexts of retinal biology, in the context of maintaining retinal homeostasis and protecting the retina from insults, for their ability to regenerate the retina in some permissive species, and in their contributions to retinal pathology. With the original research described in this dissertation, I highlight three different research models that demonstrate the wide array of functionality and diversity of Müller glia in the retina, while also characterizing consequences of their activity on other resident cell types. I describe three properties of the Müller glia we have been characterizing in the Thummel Lab in which Müller glia “save the day” by regenerating in response to acute phototoxic lesion (Chapter 1), when they “fail to play” in response to a recently developed model of chronic low light exposure (Chapter 2), and when they “go astray” as demonstrated by their prominence in pathological epiretinal membrane specimens (Chapter 3). I then describe some of the ongoing characterization studies on the aging retina in the regenerative capable zebrafish, as well as future directions for functional studies to further characterize the pathways governing proper photoreceptor differentiation in the regeneration model. Lastly, future directions to elucidate the pathogenic mechanisms underlying human epiretinal membrane development is discussed.
Recommended Citation
Kramer, Ashley C., "From Bedside To Bench: Investigating Retinal Regeneration In Zebrafish And Employing New Techniques To Study Human Retinal Pathology" (2025). Wayne State University Dissertations. 4161.
https://digitalcommons.wayne.edu/oa_dissertations/4161