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L. Arneson, M. Gleeson, V. Connaughton; Induction of Hyperglycemia and Microvascular Retinal Complications in Zebrafish, Danio rerio . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1739.
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Diabetes mellitus affects over 16 million Americans yearly, resulting in hyperglycemia and microvascular complications including retinopathy, neuropathy and nephropathy. Animal models have been developed to examine the immunological aspects of type I diabetes and the pathogenic mechanisms associated with diabetic retinopathy, but the methods of diabetes induction raise concerns regarding these models. The zebrafish, Danio rerio, has been an important animal model in developmental biology and is increasingly being used in the study of human disease.
We are currently developing zebrafish as a model system to be used to study onset, course and pharmacological therapy of diabetic retinopathy.
We have induced hyperglycemia in zebrafish by alternately immersing the fish in a glucose solution or in water. This protocol results in repeated blood glucose spikes, mimicking those experienced by an individual with diabetes. Whole eyes have been dissected from fish at various time points (days) following initial immersion in glucose solutions. Eyes were then sectioned and analyzed by immunocytochemistry to examine retinal layer thickness and induction of apoptosis.
Immersion of zebrafish in 2% to 2.5% glucose solutions results in induction of hyperglycemia, defined as a blood glucose level three times normal levels. We are currently examining the retina of hyperglycemic fish for increased rates of apoptosis resulting in decreased thickness of retinal layers.
The visual system of zebrafish is very similar to that of mammals and has been extensively studied. Therefore, zebrafish may serve as an excellent model system in which to study retinal disease associated with diabetes–induced hyperglycemia. Our work in developing this model may facilitate its future use to examine the efficacy of new pharmaceutical treatments.
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