Author ORCID Identifier
https://orcid.org/0000-0001-5887-5959
Date Available
12-13-2024
Year of Publication
2024
Document Type
Doctoral Dissertation
Degree Name
Doctor of Philosophy (PhD)
College
Arts and Sciences
Department/School/Program
Biology
Advisor
Dr. Ann C. Morris
Abstract
The retina is a complex tissue with six types of neurons, supported by an intrinsic glia cell, that work in concert to input a visual stimulus and relay a visual message to the brain. Efficient communication between neurons is vital to this process and each neuron plays a significant role in vision. When retinal neurons degenerate, that visual signal is lost. Degenerative eye diseases affect the neurons of the retina in millions of people world-wide and can ultimately lead to blindness. While treatments are evolving, most are designed to prevent further damage; the field has yet to piece together how to reverse the damage or regenerate lost neurons. Unlocking the key to neuron regeneration could restore vision. Decades of research have been dedicated to studying the mechanisms of retinal regeneration, but much is unknown. The current animal models have contributed significantly towards this goal, however, currently there is no published reports of a mammal that can regenerate retinal neurons. Identifying a mammal with a propensity for regeneration might help further the goal of restoring vision loss in retinal regenerative disease.
Spiny mice (genus Acomys) include over 15 species and are small desert rodents residing throughout Africa, the Middle East, and Southwest Asia. Several Acomys species have been reported to have regenerative abilities, a rare trait in mammals. Studies report their ability to regenerate each layer of skin, as well as the kidney, heart, and importantly, the spinal cord. This raises the question of whether they can regenerate retinal neurons. Accordingly, this dissertation describes the retinal neuroanatomy of the spiny mouse and investigates their response to retinal damage.
Chapter 1 of this dissertation is an overview of retinal biology, disease and repair. Chapter 2 focuses on characterizing Acomys retinal neuroanatomy. In this work, I described their retinal organization and cell type composition for the first time, and established a panel of antibodies that reliably detect retinal cell types in Acomys. Chapter 3 focuses on the regenerative potential of Acomys. I show that after damage to retinal neurons, Acomys mounts a pro-regenerative response that is characterized by increased cell proliferation, reduced fibrosis, and expression of factors associated with retinal regeneration. Finally, Chapter 4 provides an in-depth discussion of my results, ideas for future studies, and places my work within the broader context of the retinal regeneration field.
Digital Object Identifier (DOI)
https://doi.org/10.13023/etd.2024.501
Funding Information
National Science Foundation Graduate Research Fellowship. 2020-2025
Retina Research Foundation Pilot Study Grant, 2021-2024
Biology Department Ribble Pilot Grant 2020, 2022, 2023
Biology Department Morgan Fellowship, 2023
Recommended Citation
Bills, Jessica D., "All eyes on the spiny mouse: an investigation into Acomys dimidiatus as a model for retinal biology and regeneration" (2024). Theses and Dissertations--Biology. 110.
https://uknowledge.uky.edu/biology_etds/110
