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Marta Ugarte, Garth J. Cooper, Paul N. Bishop; TETA, A Selective Cu2+ Chelator, Prevents Neurovascular Injury In Streptozotocin-Induced Diabetic Rats. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5966.
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© ARVO (1962-2015); The Authors (2016-present)
TETA (Triethylenetetramine) is a copper chelator that is currently used as a therapeutic to treat Wilson’s disease. Recent studies have shown that TETA can ameliorate nephropathy and heart failure in diabetic rats, and diabetes-induced left-ventricular hypertrophy in a small clinical trial. The purpose of the current study was to investigate, using a rodent model, whether TETA can slow down the progression of diabetic retinopathy.
All experimental procedures were carried out in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. Diabetes was induced in rats using streptozotocin. Diabetic and non-diabetic rats were given oral TETA (20 mg/once day) by gavage. Control diabetic and non-diabetic rats were not treated with TETA, but otherwise maintained under identical conditions. After 6 weeks of diabetes ERGs were performed under general anaesthesia. After 12 weeks of diabetes, the animals were sacrificed. Retinal vascular permeability was assessed by measuring the concentration of IgG in the retina, and of fluorescein-labelled BSA two hours after intravenous injection. The total retinal content of copper and zinc was quantified using inductively coupled plasma mass spectrometry (ICP-MS).
TETA treatment resulted in decreased ERG b-wave and oscillatory potentials amplitudes in non-diabetic animals; this was statistically significant in the case of the oscillatory potentials (p=0.009, multivariate ANOVA). Diabetes produced a much larger decrease in these ERG parameters (p=0.0001), but this was prevented by TETA treatment (p=0.05) i.e. levels were restored to those of TETA-treated, non-diabetic animals. TETA significantly decreased diabetes-induced leakage of fluorescein-BSA and IgG into the retina, so that there was no statistical difference between non-diabetic and TETA-treated diabetic animals (p=0.015, multivariate ANOVA). TETA did not influence the levels of glycaemic control in the diabetic rats. Diabetes resulted in an increase in copper and zinc in the retina, which was partially ameliorated by TETA.
These data suggest that TETA can prevent diabetic retinopathy in the rat and has potential applications as a therapeutic to treat diabetic complications including retinopathy.
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