title: Evidence for diffuse central retinal edema in vivo in diabetic male Sprague Dawley rats.
abstract: BACKGROUND
  Investigations into the mechanism of diffuse retinal edema in diabetic subjects have been limited by a lack of animal models and techniques that co-localized retinal thickness and hydration in vivo. In this study we test the hypothesis that a previously reported supernormal central retinal thickness on MRI measured in experimental diabetic retinopathy in vivo represents a persistent and diffuse edema.
  
  
  RESULTS
  In diabetic and age-matched control rats, and in rats experiencing dilutional hyponatremia (as a positive edema control), whole central retinal thickness, intraretinal water content and apparent diffusion coefficients (ADC, 'water mobility') were measured in vivo using quantitative MRI methods. Glycated hemoglobin and retinal thickness ex vivo (histology) were also measured in control and diabetic groups. In the dilutional hyponatremia model, central retinal thickness and water content were supernormal by quantitative MRI, and intraretinal water mobility profiles changed in a manner consistent with intracellular edema. Groups of diabetic (2, 3, 4, 6, and 9 mo of diabetes), and age-matched controls were then investigated with MRI and all diabetic rats showed supernormal whole central retinal thickness. In a separate study in 4 mo diabetic rats (and controls), MRI retinal thickness and water content metrics were significantly greater than normal, and ADC was subnormal in the outer retina; the increase in retinal thickness was not detected histologically on sections of fixed and dehydrated retinas from these rats.
  
  
  CONCLUSIONS
  Diabetic male Sprague Dawley rats demonstrate a persistent and diffuse retinal edema in vivo, providing, for the first time, an important model for investigating its pathogenesis and treatment. These studies also validate MRI as a powerful approach for investigating mechanisms of diabetic retinal edema in future experimental and clinical investigations.
authors.affiliation: Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States of America. baberko@med.wayne.edu
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Berkowitz
authors.forename: David
authors.initials: D
authors.lastname: Bissig
authors.forename: Yongquan
authors.initials: Y
authors.lastname: Ye
authors.forename: Puja
authors.initials: P
authors.lastname: Valsadia
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Kern
authors.forename: Robin
authors.initials: R
authors.lastname: Roberts
mesh_terms: D000818:Animals; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D004058:Diffusion; D006442:Glycated Hemoglobin / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D010211:Papilledema / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000473:pathology / Q000503:physiopathology
chemical_list: D006442:Glycated Hemoglobin