Cellular and molecular pathways involved in Vascular Endothelial Growth Factor induced retinal angiogenesis

Pauline Van Eeden

    Research output: ThesisDoctoral Thesis

    243 Downloads (Pure)

    Abstract

    The increasing incidence of diabetes in our community is a significant health concern, the long term complications that will result from the rising number of cases will place a huge burden on the health system and financial burden on the community. Diabetic retinopathy is currently treated using laser therapy which, although moderately effective, is accompanied by detrimental side effects. Alternative treatments are therefore needed to improve patient outcomes. A significant problem is that the mechanisms of development of diabetic retinopathy are not well understood. In order to gain a better understanding of disease progression a common approach is to observe the changes which occur in animal models. However, to date animal models have failed to provide a fully appropriate comparison to human diabetic retinopathy. I have charted the progression of pathology in a novel murine transgenic model shows some key vascular developmental changes that mimic the changes seen in human diabetic retinopathy. The tr029VEGF model shows changes similar to non-proliferative diabetic retinopathy as well as early changes seen in proliferative diabetic retinopathy, including formation of microaneurysms, haemorrhage, oedema, neovascularisation and retinal detachment. This model is therefore useful for gaining an understanding of the mechanisms involved in the pathological progression of neovascularisation in the retina. This thesis focuses on the molecular changes in the retina of tr029VEGF model by charting the course of vascular changes during development and marrying this with molecular markers known to be involved either directly or indirectly with angiogenesis. My results show that Rhodopsin and VEGF transgene expression commences around day 5, and increase over time. Moreover, changes in retinal pathology such as reduction in photoreceptors are shown to additionally affect levels of expression of rhodopsin and VEGF.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Publication statusUnpublished - 2011

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