Cell penetrating peptide for ocular drug delivery

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dc.contributor.advisor Rupenthal, ID en
dc.contributor.advisor Green, CR en
dc.contributor.advisor Acosta, ML en
dc.contributor.author Coutinho, Frazer en
dc.date.accessioned 2019-03-13T19:25:08Z en
dc.date.issued 2018 en
dc.identifier.uri http://hdl.handle.net/2292/45981 en
dc.description.abstract Background and Aim: Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in the ageing population of the developed world. Choroidal neovascularisation (CNV), the hallmark of neovascular AMD, results in the loss of sharp central vision due to breakdown of the blood retinal barrier (BRB), unregulated blood vessel proliferation and vascular leak, particularly into the macula of the retina. The inflammatory and hypoxic pathology of neovascular AMD has been linked to uncontrolled Connexin43 (Cx43) hemichannel (HC) opening in the retina and the vasculature of the eye, leading to cell death, vascular permeability and vision loss. Cx43 HC block has proven to be effective in inhibiting the inflammatory cascade in various in vitro and in vivo ocular models. Gap19 is an intracellularly acting connexin mimetic peptide, said to be Cx43 HC specific without effecting cell-to-cell communication. Gap19, however, has low cell permeability. To improve cell uptake, Gap19 was fused with the cell penetrating peptide, Xentry, which specifically binds to cell surface expressed Syndecan-4 receptors that are upregulated in inflammatory and hypoxic injury. Therefore, the overall hypothesis of this thesis is that the fusion peptide Xentry-Gap19 (XG19) is targeted specifically to injured cells in neovascular AMD to restore vascular normality and repair the BRB without affecting healthy cells. en
dc.publisher ResearchSpace@Auckland en
dc.relation.ispartof PhD Thesis - University of Auckland en
dc.relation.isreferencedby UoA99265133711402091 en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/3.0/nz/ en
dc.title Cell penetrating peptide for ocular drug delivery en
dc.type Thesis en
thesis.degree.discipline Biomedical Sciences en
thesis.degree.grantor The University of Auckland en
thesis.degree.level Doctoral en
thesis.degree.name PhD en
dc.rights.holder Copyright: The author en
dc.rights.accessrights http://purl.org/eprint/accessRights/OpenAccess en
pubs.elements-id 766179 en
pubs.record-created-at-source-date 2019-03-14 en


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