• Login
    View Item 
    •   Home
    • UA Graduate and Undergraduate Research
    • UA Theses and Dissertations
    • Dissertations
    • View Item
    •   Home
    • UA Graduate and Undergraduate Research
    • UA Theses and Dissertations
    • Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UA Campus RepositoryCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsPublisherJournalThis CollectionTitleAuthorsIssue DateSubmit DateSubjectsPublisherJournal

    My Account

    LoginRegister

    About

    AboutUA Faculty PublicationsUA DissertationsUA Master's ThesesUA Honors ThesesUA PressUA YearbooksUA CatalogsUA Libraries

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Prostaglandin Involvement in the Conventional Outflow Pathway

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    azu_etd_11335_sip1_m.pdf
    Size:
    1.695Mb
    Format:
    PDF
    Download
    Author
    Millard, Lindsey Highstrom
    Issue Date
    2010
    Keywords
    Glaucoma
    Outflow facility
    Prostaglandins
    Advisor
    Stamer, William D.
    
    Metadata
    Show full item record
    Publisher
    The University of Arizona.
    Rights
    Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
    Abstract
    Prostaglandins (PG) play a major role in many endogenous processes including inflammation, labor, reproduction, and blood clotting. In the last two decades, these lipid signaling molecules have shown great potential as ocular hypotensive agents. Intraocular pressure (IOP) is a major risk factor in primary open-angled glaucoma (POAG), the second leading cause of blindness world-wide. Currently, prostaglandin F(2α) analogues are the most widely prescribed medications used to treat ocular hypertension. Studies have identified that almost all prostaglandin analogues exhibit anti-hypertensive effects in the eye, although they are not clinically available. Initial studies attributed the decrease in IOP observed to changes in hydraulic conductivity across the pressure-independent or uveoscleral pathway. More recent studies have shown that prostaglandin F(2α) analogues also lower IOP by affecting the pressure-dependent or trabecular pathway--the diseased tissue in POAG. Little is currently known about PG endogenous function, or the etiology of POAG. However, these studies suggest prostaglandin involvement in the maintenance of IOP in humans and identify the potential of PG analogues to treatment ocular hypertension. The research and findings presented in this dissertation address three specific aims designed to test the hypothesis that Endogenous prostaglandins, prostaglandin enzymes and prostaglandin receptors are involved in regulating conventional outflow facility. Specific aim 1 characterizes the distribution and activity of prostamide/prostaglandin F synthase (PM/PGFS) in the mouse and human eye using immunohistochemistry, western blot analysis and thin layer chromatography. Using techniques in biochemistry, molecular biology and physiology, specific aim 2, identifies the presence of the PG-EP₄ receptor within the outflow pathways, and the efficacy of a selective PG-EP₄ agonist, 3,7-dithiPGE₁, is also determined. Finally, specific aim 3 identifies PG-EP4 receptor coupling and downstream signaling using in vitro assays of transfected and primary cell lines to measure cAMP accumulation after treatment with a PG-EP₄ agonist. Collectively, these studies reveal the importance of PGE₂ synthesis and signaling to the conventional outflow pathway. They identify the PG-EP₄ receptor as a regulator of aqueous outflow and provide more specific therapeutic targets for the treatment of POAG.
    Type
    Electronic Dissertation
    text
    Degree Name
    Ph.D.
    Degree Level
    doctoral
    Degree Program
    Graduate College
    Medical Pharmacology
    Degree Grantor
    University of Arizona
    Collections
    Dissertations

    entitlement

     
    The University of Arizona Libraries | 1510 E. University Blvd. | Tucson, AZ 85721-0055
    Tel 520-621-6442 | repository@u.library.arizona.edu
    DSpace software copyright © 2002-2017  DuraSpace
    Quick Guide | Contact Us | Send Feedback
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.