title: Manganese-Enhanced MRI for Preclinical Evaluation of Retinal Degeneration Treatments.
abstract: OBJECTIVE
  Apply manganese-enhanced magnetic resonance imaging (MEMRI) to assess ion channel activity and structure of retinas from mice subject to light-induced retinal degeneration treated with prophylactic agents.
  
  
  METHODS
  Abca4(-/-)Rdh8(-/-) double knockout mice with and without prophylactic retinylamine (Ret-NH2) treatment were illuminated with strong light. Manganese-enhanced MRI was used to image the retina 2 hours after intravitreous injection of MnCl2 into one eye. Contrast-enhanced MRIs of the retina and vitreous humor in each experimental group were assessed and correlated with the treatment. Findings were compared with standard structural and functional assessments of the retina by optical coherence tomography (OCT), histology, and electroretinography (ERG).
  
  
  RESULTS
  Manganese-enhanced MRI contrast in the retina was high in nonilluminated and illuminated Ret-NH2-treated mice, whereas no enhancement was evident in the retina of the light-illuminated mice without Ret-NH2 treatment (P < 0.0005). A relatively high signal enhancement was also observed in the vitreous humor of mice treated with Ret-NH2. Strong MEMRI signal enhancement in the retinas of mice treated with retinylamine was correlated with their structural integrity and function evidenced by OCT, histology, and a strong ERG light response.
  
  
  CONCLUSIONS
  Manganese-enhanced MRI has the potential to assess the response of the retina to prophylactic treatment based on the measurement of ion channel activity. This approach could be used as a complementary tool in preclinical development of new prophylactic therapies for retinopathies.
authors.affiliation: Department of Biomedical Engineering School of Engineering, Case Western Reserve University, Cleveland, Ohio, United States.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Schur
authors.affiliation: Department of Biomedical Engineering School of Engineering, Case Western Reserve University, Cleveland, Ohio, United States.
authors.forename: Li
authors.initials: L
authors.lastname: Sheng
authors.affiliation: Department of Ophthalmology and Visual Sciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States.
authors.forename: Bhubanananda
authors.initials: B
authors.lastname: Sahu
authors.affiliation: Department of Biomedical Engineering School of Engineering, Case Western Reserve University, Cleveland, Ohio, United States.
authors.forename: Guanping
authors.initials: G
authors.lastname: Yu
authors.affiliation: Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States.
authors.forename: Songqi
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Biomedical Engineering School of Engineering, Case Western Reserve University, Cleveland, Ohio, United States.
authors.forename: Xin
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Ophthalmology and Visual Sciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States 3Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States.
authors.forename: Akiko
authors.initials: A
authors.lastname: Maeda
authors.affiliation: Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Palczewski
authors.affiliation: Department of Biomedical Engineering School of Engineering, Case Western Reserve University, Cleveland, Ohio, United States.
authors.forename: Zheng-Rong
authors.initials: ZR
authors.lastname: Lu
mesh_terms: D000818:Animals; D002712:Chlorides; D003623:Dark Adaptation; D004195:Disease Models, Animal; D004596:Electroretinography; D005260:Female; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D017895:Manganese Compounds; D051379:Mice; D018345:Mice, Knockout; D012160:Retina / Q000473:pathology* / Q000503:physiopathology; D012162:Retinal Degeneration / Q000175:diagnosis* / Q000503:physiopathology; D041623:Tomography, Optical Coherence / Q000379:methods
chemical_list: D002712:Chlorides; D017895:Manganese Compounds; C025340:manganese chloride