Date of Award

Spring 5-15-2020

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Neurosciences)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

Retinal degenerative diseases are a major cause of morbidity in modern society because visual impairment significantly decreases the quality of life of patients. A significant challenge in treating retinal degenerative diseases is their genetic and phenotypic heterogeneity. Furthermore, limitations in our understanding of disease pathophysiology have led to reliance on therapies that often treat disease endpoints rather than addressing disease etiology and/or pathophysiology. The long-term goal of my thesis research was to provide molecular and cellular insights into the pathophysiology underlying diverse retinal degenerative diseases, which may lead to much-needed, novel therapeutic approaches. During the first part of my thesis research, I discovered that impaired NAD+ homeostasis is a central feature of diverse retinal degenerative diseases (Chapter 2). For the second part of my thesis research, I found that the central cellular phenotype of aged macrophages, which are known to promote age-related macular degeneration, is impaired cholesterol homeostasis (Chapter 3) and that the transition towards this disease-promoting, aged phenotype is regulated, in part, by microRNA-150 (Chapter 4). Although further research is necessary to translate these findings to the bedside, they have the potential to transform care for patients with retinal degenerative diseases.

Language

English (en)

Chair and Committee

Rajendra S. Apte

Committee Members

Aaron DiAntonio, Vladimir J. Kefalov, Daniel S. Ory, Rithwick Rajagopal,

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