Pituitary Adenylate Cyclase Activating Polypeptide and Its Receptor as Novel Therapeutic Targets for Opioid Induced Hyperalgesia

Date of Award

3-5-2025

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

Inflammation is an essential response to injury as it clears necrotic tissue or pathogens. The acute inflammatory response is followed by repair mechanisms that regenerate the injured tissue such that normal function can be restored. Though the eye is normally a site of immune privilege, in some pathologic contexts immune cells gain access to the eye and can cause irreversible vision loss. The overarching goal of this work is to better understand the mechanisms underlying ocular inflammation and tissue regeneration to identify novel therapeutic targets to treat blinding diseases. In the first part of my thesis research, I elucidated the cellular consequences of macrophage deficiency of stearoyl-CoA desaturase 2, a fatty acid enzyme whose downregulation in aging could contribute to inflammation in age-related macular degeneration (Chapter 2). In the second part of my thesis research, I identified that CYR61 signaling could contribute to immune cell recruitment & activation in age-related macular degeneration (Chapter 3). In the final part of my thesis work, I characterized the stem cells that accomplish renewal and repair of the corneal epithelium (Chapter 4). The findings enclosed provide a roadmap for therapeutic development for blinding diseases.

Language

English (en)

Chair and Committee

Rajendra Apte

Committee Members

Andrew Huang; Indira Mysorekar; Kory Lavine; Philip Williams; Todd Margolis

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