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      Impaired apparent ion demand in experimental diabetic retinopathy: correction by lipoic Acid.

      Investigative ophthalmology & visual science

      Animals, Antioxidants, therapeutic use, Blood-Retinal Barrier, Capillary Permeability, Diabetes Mellitus, Experimental, complications, metabolism, Diabetic Retinopathy, drug therapy, etiology, Female, Hyperglycemia, Magnetic Resonance Imaging, Male, Manganese, Rats, Rats, Inbred Lew, Rats, Sprague-Dawley, Retina, drug effects, pathology, Spectrometry, Mass, Electrospray Ionization, Thioctic Acid

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          Abstract

          To test the hypothesis that early in the course of diabetes, apparent ion demand within the retina is impaired and may be corrected by alpha-lipoic acid (LPA), a drug that inhibits vascular histopathology. Intraretinal manganese ion uptake and retinal thickness were measured from high-resolution manganese-enhanced MRI (MEMRI) data of control and streptozocin diabetic male Sprague-Dawley (SD) rats and of control and diabetic female Lewis rats with and without treatment with LPA. In a subgroup of male SD rats, blood-retinal barrier (BRB) integrity was also assessed with dynamic contrast-enhanced MRI. In addition, ion-coupled plasma-mass spectrometry (ICP-MS) was used to measure baseline whole manganese levels from retinas of control and diabetic rats. Manganese ion uptake by receptor and postreceptor retina was subnormal in each untreated diabetic groups, and these deficiencies could be corrected with LPA treatment. ICP-MS studies found no differences in baseline retinal manganese concentration between control and diabetic rats. In 3-month-old diabetic male SD rats, total and postreceptor retinal thickness increased (P < 0.05) without loss of BRB integrity. In contrast, in untreated and treated diabetic female Lewis rats, retinal thicknesses were normal. The present results support the hypothesis that LPA can correct the impaired apparent ion demand in experimental diabetic retinopathy.

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          Journal
          17898301
          10.1167/iovs.07-0433

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