title: Oxidative stress and light-evoked responses of the posterior segment in a mouse model of diabetic retinopathy.
abstract: OBJECTIVE
  To test the hypothesis that in a mouse model of diabetic retinopathy, oxidative stress is linked with impaired light-evoked expansion of choroidal thickness and subretinal space (SRS).
  
  
  METHODS
  We examined nondiabetic mice (wild-type, wt) with and without administration of manganese, nondiabetic mice deficient in rod phototransduction (transducin alpha knockout; GNAT1(-/-)), and diabetic mice (untreated or treated with the antioxidant α-lipoic acid [LPA]). Magnetic resonance imaging (MRI) was used to measure light-evoked increases in choroidal thickness and the apparent diffusion coefficient (ADC) at 88% to 100% depth into the retina (i.e., the SRS layer).
  
  
  RESULTS
  Choroidal thickness values were similar (P > 0.05) between all untreated nondiabetic dark-adapted groups and increased significantly (P < 0.05) with light; this expansion was subnormal (P < 0.05) in both diabetic groups. Apparent diffusion coefficient values in the SRS layer robustly increased (P < 0.05) in a light duration-dependent manner, and this effect was independent of the presence of Mn(2+). The light-stimulated increase in ADC at the location of the SRS was absent in GNAT1(-/-) and diabetic mice (P > 0.05). In diabetic mice, the light-dependent increase in SRS ADC was significantly (P < 0.05) restored with LPA.
  
  
  CONCLUSIONS
  Apparent diffusion coefficient MRI is a sensitive method for evaluating choroid thickness and its light-evoked expansion together with phototransduction-dependent changes in the SRS layer in mice in vivo. Because ADC MRI exploits an endogenous contrast mechanism, its translational potential is promising; it can also be performed in concert with manganese-enhanced MRI (MEMRI). Our data support a link between diabetes-related oxidative stress and rod, but not choroidal, pathophysiology.
authors.affiliation: Department of Anatomy and Cell Biology, Wayne State University, Detroit, Michigan, United States Department of Ophthalmology, Wayne State University, Detroit, Michigan, United States.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Berkowitz
authors.affiliation: Department of Anatomy and Cell Biology, Wayne State University, Detroit, Michigan, United States.
authors.forename: Edmund Michael
authors.initials: EM
authors.lastname: Grady
authors.affiliation: Department of Anatomy and Cell Biology, Wayne State University, Detroit, Michigan, United States.
authors.forename: Nikita
authors.initials: N
authors.lastname: Khetarpal
authors.affiliation: Department of Anatomy and Cell Biology, Wayne State University, Detroit, Michigan, United States.
authors.forename: Akshar
authors.initials: A
authors.lastname: Patel
authors.affiliation: Department of Anatomy and Cell Biology, Wayne State University, Detroit, Michigan, United States.
authors.forename: Robin
authors.initials: R
authors.lastname: Roberts
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002829:Choroid / Q000473:pathology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003930:Diabetic Retinopathy / Q000503:physiopathology*; D005260:Female; D008027:Light; D008279:Magnetic Resonance Imaging; D008297:Male; D008345:Manganese / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009929:Organ Size; D018384:Oxidative Stress / Q000502:physiology*; D012160:Retina / Q000473:pathology*; D008063:Thioctic Acid / Q000494:pharmacology; D014785:Vision, Ocular / Q000502:physiology*
chemical_list: D000975:Antioxidants; D008345:Manganese; D008063:Thioctic Acid
keywords: MRI; choroid; choroidal thickness; diffusion; phototransduction; retina; water