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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.

Additional file 1.

The Drosophila larval nervous system is radically restructured during metamorphosis to produce adult specific neural circuits and behaviors. Genesis of new neurons, death of larval neurons and remodeling of those neurons that persistent collectively act to shape the adult nervous system. Here, we examine the fate of a subset of larval motor neurons during this restructuring process. We used a dHb9 reporter, in combination with the FLP/FRT system to individually identify abdominal motor neurons in the larval to adult transition using a combination of relative cell body location, axonal position, and muscle targets. We found that segment specific cell death of some dHb9 expressing motor neurons occurs throughout the metamorphosis period and continues into the post-eclosion period. Many dHb9 > GFP expressing neurons however persist in the two anterior hemisegments, A1 and A2, which have segment specific muscles required for eclosion while a smaller proportion also persist in A2-A5. Consistent with a functional requirement for these neurons, ablating them during the pupal period produces defects in adult eclosion. In adults, subsequent to the execution of eclosion behaviors, the NMJs of some of these neurons were found to be dismantled and their muscle targets degenerate. Our studies demonstrate a critical continuity of some larval motor neurons into adults and reveal that multiple aspects of motor neuron remodeling and plasticity that are essential for adult motor behaviors. (C) 2016 Wiley Periodicals, Inc.