The effects of systemic endotoxaemia on the retina of the Ins2Akita mouse model type 1 diabetes

Nermina Nina Vagaja

Research output: ThesisDoctoral Thesis

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[Truncatd abstract] Retinal inflammation is an important underlying mechanism of chronic glucotoxic injury in diabetic retinopathy (DR), which also involves neurodegeneration, microglial activation and remodeling of the microvasculature. In the central nervous system (CNS), acute systemic exposure to pathogens or their byproducts accelerates neurodegeneration via excessive activation and cytotoxicity of "primed" microglia, classically MHC class It, which are reprogrammed for abnormal responses by the underlying pathology. Although diabetes predisposes to some infections, the impact of peripheral infections on the onset and progression of DR is presently unknown, as it is not clear whether diabetes can reprogram retinal microglia and other resident macrophages to cause excessive or cytotoxic responses to systemic pathogens. If a detrimental effect of peripheral infections on the diabetic retina was confirmed, this could have clinical significance for diabetic subjects exposed to pathogens. It may also accelerate the progression and increase the severity of DR in diabetic mice, where pathology is usually restricted to very early disease. This study evaluated for the first time whether differences exist in activation responses of retina-associated microglia, vitreal hyalocytes, and related tissue injury between a diabetic mouse without detectable retinopathy (Ins2Akita mouse) and its non-diabetic littermates (C57BLl6; WT). Acute (single injection at seven weeks of age) and chronic (three fortnightly injections between 12-18 weeks of age) activation responses following intraperitoneal injection of ultra-pure Toll-like receptor 4 (TLR4) agonist Escherichia coli lipopolysaccharide (LPS, 91lg/g body weight) were assessed and compared to PBS-injected controls...
Original languageEnglish
QualificationDoctor of Philosophy
Publication statusUnpublished - 2011


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