Inflammatory biomarkers in the eye

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.