Ocular neovascularization (NV) associated with corneal NV, ischemic retinopathies and age-related macular degeneration is a leading cause of severe vision loss. While numerous contributing factors have been identified, the potential role of the CD36 scavenger receptor has been largely overlooked notwithstanding its crucial involvement in normal retinal function. Accordingly, the central aim of this work was to elucidate the contribution and regulation of CD36 during ocular NV using the cornea as a model. / Initial work investigating the role of CD36 10 maintaining corneal avascularity, an important feature of the normal cornea, revealed that genetic ablation of CD36 elicits age-related corneal NV. Subsequent studies using a pathophysiologically relevant model of inflammatory corneal NV showed constitutive expression of CD36 in the normal cornea with marked induction in the neovascularized cornea. Importantly, activation of CD36 suppressed and induced regression of corneal NV, effects that proceeded via concerted inhibition of VEGFA, JNK-1, and cJun. / Because hypoxia is a fundamental stimulus for angiogenesis, it was pertinent to explore the role and regulation of CD36 during hypoxia. We demonstrate that CD36 expression was significantly elevated in hypoxia-exposed corneal and retinal tissue and in hypoxic retinal pigment epithelial cells. Essential contributions of hypoxia-inducible factor (HIF)-1 and reactive oxygen species were also established. Functional consequences were depicted by augmentations in CD36 phagocytic and anti-angiogenic activities. / Collectively, data disclose CD36 as an important modulator of corneal avascularity and inflammatory corneal NV; this imparts several interesting avenues for future research on the involvement of CD36 in neovascular diseases of the eye. Novel data further identify CD36 as a hypoxia and HIF-1 regulated gene thus creating a framework for future elucidation of the regulatory aspects of this receptor.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.115899 |
| Date | January 2008 |
| Creators | Mwaikambo, Bupe Rose. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Pharmacology & Therapeutics.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002827134, proquestno: AAINR66689, Theses scanned by UMI/ProQuest. |
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