Diabetic retinopathy (DR) is the leading cause of blindness in working age Americans. The early stages of DR pathogenesis include chronic inflammation, which can eventually lead to the development of later stages of the disease characterized by pathologic pre-retinal neovascularization. The first goal of this dissertation was to determine diabetes-relevant culture conditions for which to test the effect of a novel class of anti-inflammatory lipids, the epoxygenated fatty acids. Epoxygenated fatty acids of the epoxyeicosatrienoic acid (EET) family and epoxydocosapentaenoic acid (EDP) family are generated by cytochrome P450 epoxygenase enzymes. EET and EDP have been shown to be anti-inflammatory, but their levels are limited by the hydrolysis to diol products by the soluble epoxide hydrolase enzyme (sEH). Thus, the second goal of this dissertation was to determine whether restoration of epoxide levels through exogenous addition and inhibition of their metabolism by sEH was able to inhibit retinal vascular inflammation. However, EETs have been shown to exert pro-angiogenic activities, which would be contraindicated for the late stages of DR. Therefore, the final goal was to determine whether EETs were involved in hypoxia-induced retinal neovascularization.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-12152016-114704 |
| Date | 15 December 2016 |
| Creators | Capozzi, Megan Elise |
| Contributors | Ann Richmond, Milam A. Brantley Jr., Ambra Pozzi, John S. Penn, Roger J. Colbran |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-12152016-114704/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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