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Title: The therapeutic potential of erythropoietin for ischaemic retinopathies
Author: O'Leary, Olivia Eileen
ISNI:       0000 0004 5992 6537
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2015
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Ischaemic retinopathies are characterised by dysfunction and degeneration of retinal vascular networks, leading to the compensatory development of sight-threatening vasoproliferative pathology. The scope for treating these diseases is limited and, as such, they continue to represent a significant cause of visual impairment globally. Erythropoietin (EPO) has demonstrated tissue-protective abilities in ischaemic injury, settings, but its clinical use is precluded by concerns that it could lead to thromboembolic events or exacerbate pathological retinal angiogenesis. ARA 290, a peptide based on the B helix of EPO, is non-erythropoietic whilst maintaining tissue-protective properties. We hypothesised that ARA 290 could be used as a novel therapeutic to target multiple facets of ischaemic retinopathies. To test this hypothesis, we investigated the potential of ARA 290 for use either as a stand-alone pharmacotherapy to prevent vasodegeneration, or to stimulate microvascular repair, in conjunction with endothelial colony forming cells (ECFCs), a vasculogenic endothelial progenitor cell subpopulation. The vasoprotective potential of ARA 290 in the context of retinopathy of prematurity was investigated in a preventive paradigm, using a murine model of hyperoxia-induced retinal vasodegeneration. In this context, ARA 290 was found to be unsuitable as a vasoprotective monotherapy. In the STZ-induced diabetic mouse ARA 290 administered three times weekly for the duration of hyperglycaemia was associated with preservation of retinal function and reduction in retinal inflammation, as evidenced by reduced Müller gliosis and the reduced gene expression of a panel of inflammatory markers. ECFCs were isolated from human umbilical cord blood monocytes cultured on collagen. In the murine oxygen-induced retinopathy (OIR) model of retinal ischaemia, vasorepair by ECFCs was enhanced in the presence of ARA 290. These studies provide important insight into the potential application of ARA 290 as a novel therapeutic for the ischaemic retina.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available