Dissertation
Inflammatory biomarkers in the eye
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Spring 2022
DOI: 10.25820/etd.006532
Abstract
Inflammation within the eye (intraocular inflammation) is a major cause of disability and blindness worldwide and is directly or indirectly associated with many eye diseases. However, treatment options for intraocular inflammation are very limited, often relying on imprecise therapies, such as corticosteroid management, with high risks of ocular and systemic side effects with limited effectiveness. These treatment difficulties are reflected in the high cost of medical care for patients suffering from intraocular inflammation, which can be comparable to the costs of cancers, diabetes, and cardiovascular diseases. A poor understanding of the complex and nuanced relationship between the immune system and the eye, particularly at the molecular level, is a major impediment to developing improved, targeted therapies for intraocular inflammation. One powerful approach to address this unmet need is through the careful identification, study, and characterization of protein biomarkers in the eye. The discovery of new inflammatory protein biomarkers in the eye can lead to the development of better, more effective therapeutics to treat intraocular inflammation, as well as improve our understanding of inflammatory disease processes in the eye and elsewhere in the body. In this thesis, I discuss my work aimed at identifying and studying inflammatory protein biomarkers in the eye. In chapter two, I discuss my findings related to a fundamental inflammatory biomarker, the antibody, and demonstrate how the study of intraocular antibodies is important to ongoing human CRISPR/Cas9 gene editing clinical trials in the eye. In chapter three, I broaden my approach to inflammatory protein biomarker identification and characterization, applying proteomics (the large-scale study of proteins) to the inflammatory eye disease Age Related Macular Degeneration. In chapter four, I describe the discovery of the novel CAPN5-IRX3 interaction in the context of inflammatory eye disease and demonstrate how biomarker discovery can be taken a step further through detailed biochemical and mechanistic analyses. My scientific discoveries and contributions described herein improve our understanding of intraocular inflammation and lay the groundwork for better medical care for patients suffering from inflammation within the eye.
Details
- Title: Subtitle
- Inflammatory biomarkers in the eye
- Creators
- Marcus A Toral
- Contributors
- Vinit B. Mahajan (Advisor)Alexander G. Bassuk (Advisor)John D Colgan (Committee Member)Robert A Cornell (Committee Member)Polly J Ferguson (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Biomedical Science (Molecular Medicine)
- Date degree season
- Spring 2022
- Publisher
- University of Iowa
- DOI
- 10.25820/etd.006532
- Number of pages
- xii, 123 pages
- Copyright
- Copyright 2020 Marcus A. Toral
- Language
- English
- Description illustrations
- color illustrations
- Description bibliographic
- Includes bibliographical references (pages 111-123).
- Public Abstract (ETD)
This thesis is about discovering new ways to understand and treat eye diseases, especially those eye diseases which can cause blindness. We all value our ability to see, but often we do not realize just how important it is to us until it is taken away through blindness. One of the most difficult to treat, and even incurable, ways people can become blind is when white blood cells and other parts of the immune system cause damage inside of the eye. While our immune systems are usually helpful in our bodies, they are not perfect and can become broken and make errors--just like other parts of our bodies. When this happens inside of the eye, it can cause blindness. However, one of the ways we can fix a broken immune system is by creating new drugs that make the immune system work correctly. But not all drugs work equally well. The best drugs are those that fix only the medical problem that they are being used for without causing new medical problems. These drugs are very specific in what they do inside the body, and in order to create them we need to know exactly how the body works. My thesis discusses new and specific ways that the eye works, and how that information can be used to make new and better drugs to fix a broken immune system inside of the eye.
- Academic Unit
- Biomedical Science Program
- Record Identifier
- 9984271356202771
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