Characterisation of the akimba mouse: a model of retinal neovascularisation on a hyperglycaemic background and the in vivo study of endothelin-2 in the development of neovascularisation

Ireni Ali Rahman

Research output: ThesisDoctoral Thesis

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Abstract

[Truncated abstract] Research on diabetic retinopathy (DR) has been hampered by the lack of an animal model that exhibits not only the early stages of background DR (neurodegenerative and mild vascular changes), but progresses to the proliferative and sight-threatening stage of DR with ischaemia, retinal neovascularisation (RNV) and retinal detachment. As there are no diabetic animal models that fulfill these criteria, models of oxygeninduced retinopathy or genetically modified mouse models overexpressing growth factors involved in the pathogenesis of human DR, including insulin-like growth factor or vascular endothelial growth factor (VEGF), have been used to study DR. However, these models were all developed on a normoglycaemic background and can only be considered as models for the study of RNV, not models of DR. In the current study, a new mouse model of diabetes with severe retinopathy was generated and characterised. The Ins2Akita (Akita) Type 1 diabetic mouse which carries a spontaneous insulin 2 gene mutation was crossed with the in-house developed trVEGF029 (Kimba) mouse, where RNV is driven by photoreceptor-targeted overexpression of human VEGF165 (hVEGF165) to produce the new Akimba mouse model. The first aim of this study was to characterise the ocular pathology in the newly developed Akimba mouse. The Akimba mice not only retained the characteristics of the parental strains, such as developing hyperglycaemia and RNV, but they also demonstrated enhanced photoreceptor and ganglion cell loss, thinning of the retina and more severe retinal vascular pathology, including more severe capillary non-iiperfusion, vessel constriction, venous beading, neovascularisation, fibroses and oedema, compared to the Kimba mouse model.
Original languageEnglish
QualificationDoctor of Philosophy
Publication statusUnpublished - 2011

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