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T.W. Chang, S. Koevary; Ocular Expression of mRNA for Adrenomedullin and its Receptor in Normal and Short-Term Diabetic Rats . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3475.
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Purpose: Adrenomedullin (AM) is a vasodilating peptide produced by vascular endothelial and smooth muscle cells. Though one of its many effects is to down-regulate islet expression of insulin, studies have demonstrated that hyperglycemia increases vascular AM expression. It has also been reported that the levels of circulating AM in poorly controlled diabetics rise significantly in a pattern correlated with the development of systemic diabetic complications, suggesting that AM might play a role in diabetic disease. Since diabetic ocular disease is characterized by abnormalities in vascular endothelial cells, the principal source of AM, we set out to map AM and AM receptor (AMR) gene expression level in the eyes of normal and diabetic rats. Methods: Female Lewis rats were rendered diabetic by injection with 85 mg/kg of streptozotocin, and type 2 diabetes was confirmed by urine analysis and by blood glucose determination (>300 mg%). AM and AMR mRNA gene expression profiles were analyzed via rtPCR in the following ocular tissues: cornea, aqueous humor, iris and ciliary body, lens, vitreous humor, retina, optic nerve, and combined RPE, choroid, and sclera. Profiles from each tissue group were mapped temporally during the progression of unregulated type 2 diabetes from day 1 to day 16 and at 13 months. Results: Control rats expressed AM and AMR mRNA in their iris, ciliary body, lens, retina, and combined RPE, choroid, and sclera. However, in a change that may influence local AM function, AMR mRNA fell below detection limits in all of these tissues except the lens within 5 days of diabetes onset. Only the lens continued to express detectable levels of mRNA for both AM and AMR in rats that had unregulated type 2 diabetes for 13 months. Conclusions: These data suggest that local expression of mRNA for AM and AMR in the diabetic eye diminishes during the early course of the disease, with mRNA expression for the receptor dropping out first. However, the role of AM during development of diabetic ocular complications remains to be determined.
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