title: Retinal ion regulation in a mouse model of diabetic retinopathy: natural history and the effect of Cu/Zn superoxide dismutase overexpression.
abstract: OBJECTIVE
  To test the hypotheses that manganese-enhanced MRI (MEMRI) is useful in evaluating intraretinal ion dysregulation in wild-type (WT) and Cu/Zn superoxide dismutase (SOD1) overexpressor mice.
  
  
  METHODS
  Central intraretinal ion activity and retinal thickness were measured from high-resolution data of light- and dark-adapted WT C57BL/6 mice (to gauge MEMRI sensitivity to normal visual processing in mice) and dark-adapted diabetic and nondiabetic WT and Cu/Zn superoxide dismutase overexpressor (SOD1OE) mice. Glycated hemoglobin and retinal vascular histopathology were also determined.
  
  
  RESULTS
  In WT mice, light adaptation reduced outer retinal manganese uptake compared with that in dark adaptation; no effect on inner retinal uptake was found. In diabetic WT mice, intraretinal manganese uptake became subnormal between 1.5 and 4 months of diabetes onset and then relatively increased. Central retinal thickness, as determined with MEMRI, decreased as a function of age in diabetic mice but remained constant in control mice. Nondiabetic SOD1OE mice had normal retinal manganese uptake but subnormal retinal thickness and supernormal acellular capillary density. At 4.2 months of diabetes, SOD1OE mice had normal manganese uptake and no further thinning; acellular capillaries frequency did not increase by 9 to 10 months of diabetes.
  
  
  CONCLUSIONS
  In emerging diabetic retinopathy, MEMRI provided an analytic measure of an ionic dysregulatory pattern that was sensitive to SOD1 overexpression. The potential benefit of SOD1 overexpression to inhibit retinal abnormality in this model is limited by the retinal and vascular degeneration that develops independently of diabetes.
authors.affiliation: Department of Anatomy and Cell Biology, Wayne State University, Detroit, Michigan 48201, USA. baberko@med.wayne.edu
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Berkowitz
authors.forename: Marius
authors.initials: M
authors.lastname: Gradianu
authors.forename: David
authors.initials: D
authors.lastname: Bissig
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Kern
authors.forename: Robin
authors.initials: R
authors.lastname: Roberts
mesh_terms: D000818:Animals; D001693:Biological Transport, Active; D003623:Dark Adaptation; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D007473:Ion Channels / Q000378:metabolism*; D017136:Ion Transport; D008027:Light; D008279:Magnetic Resonance Imaging; D008297:Male; D008345:Manganese / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012160:Retina / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1
chemical_list: D007473:Ion Channels; D008345:Manganese; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1