Tesi etd-09192017-180654 |
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Tipo di tesi
Tesi di laurea magistrale
Autore
PESCE, NOEMI ANNA
URN
etd-09192017-180654
Titolo
Effects of Formyl Peptide Receptors Antagonism in humanized models of Iris Angiogenesis
Dipartimento
BIOLOGIA
Corso di studi
BIOLOGIA APPLICATA ALLA BIOMEDICINA
Relatori
relatore Dal Monte, Massimo
relatore Helder, André
relatore Helder, André
Parole chiave
- angiogenesis
- iris
Data inizio appello
23/10/2017
Consultabilità
Completa
Riassunto
Neovascular eye diseases are a major cause of blindness throughout life. The anterior eye contains one major microvascular bed: the iris microvasculature. Angiogenic diseases are characterised by the development of new blood vessels in the eye, as are the case of neovascular glaucoma (NG) and proliferative diabetic retinopathy (PDR), which can lead to rubeosis iridis, the clinical term for iris angiogenesis. These angiogenic conditions are coordinated by endothelial cells (ECs), pericytes and numerous other cellular components of the tissues. Disturbed balance of positive and negative regulatory factors secreted from these cells is the molecular basis for ocular pathologic angiogenesis. In the eye, as in many other organs, tissue hypoxia and ischemia have been suggested as major driving forces for this. Regulation of vascular factors as a response to hypoxia is mainly driven by hypoxia-inducible factor (HIF) molecules. HIF is a transcription factor which causes the activation of genes related to angiogenesis, including vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs), among several others. Moreover, regulation of angiogenesis has been suggested to differ in different tissues, which further implies the involvement of hypoxic responses of ECs, and consequently the release of stimulatory angiogenic factors. Currently, understanding similarities and divergencies in regulatory mechanisms of ECs is one of the main objectives to successfully overcome ocular angiogenic pathologies, such as NG and PDR, in the clinic. Due to their major role in the development of ocular angiogenic pathologies, ECs from affected tissues are obvious targets for research studies and drug therapies. A standard treatment for these blinding diseases involves biologic drugs (bevacizumab, ranibizumab and aflibercept) that target vascular endothelial growth factor (VEGF), the most dominant angiogenic mediator in the eye. Aims: isolation of endothelial cells from iris tissues, immortalization of those cell lines, and some characterization to elaborate molecular identity of iris endothelial cell (IEC) lines; moreover the use of organotypical cultures where ex vivo angiogenesis can be analyzed to test the angiogenic/antiangiogenic potential of different compounds, using an ex vivo model of microvascular angiogenesis.
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