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Title: Molecular and cellular factors affecting vascular patterning during retinal vascular plexus development
Author: Donaldson, Graeme
Awarding Body: Ulster University
Current Institution: Ulster University
Date of Award: 2012
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The murine retinal vasculature consists of three co-planar plexi, which develop in the first three weeks of postnatal life (PO-P20). The first to form is the superficial plexus: blood vessels migrate radially outwards from the optic nerve head (ONH) region and along the surface of the retina, guided by a template of astrocytes. This plexus reaches the retinal periphery at around P7, at which time, vertical vascular sprouts begin to project into the deep layers of the retina. Two further plexi then ramify around the inner and outer surfaces of the inner nuclear layer (INL), the deeper of which is the first to form (P7-PI2), whereas the intermediate plexus forms last (PI4-P20). During development, an immature, high calibre capillary-only plexus undergoes differentiation and remodelling to become a mature, low calibre, adult plexus with identifiable arteries and veins. In the first experimental chapter of this project, immunohistochemical (IHC) techniques were used to discover that arteriovenous differentiation is linked to a tightly-patterned process of capillary pruning by caspase-dependent endothelial cell apoptosis. IHC using EFs showed that specific spatio-temporal patterning of hypoxia occurs within the neuroblast layer during deep and intermediate plexus development. Muller glial cell (MGC) and R-Cadherin imaging showed that vertical sprouting of the plexus occurs under the guidance of MGC processes and that the spatio-temporal expression of R-Cadherin defines the locations of the plexi. The second experimental chapter showed that transgenic overexpression of vascular endothelial growth factor 188 (VEGF 188) in the eye ameliorates the vaso-obliteration and pathological neovascularisation associated with oxygen-induced retinopathy (OIR). In the third experimental chapter a novel transgenic mouse strain was created, which over-expresses the VEGFI6Sb isoform in the eye using the same promoter as the aforementioned transgenic mouse. Despite positive identification as transgenics, no ocular perturbations were found in this novel strain.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available