Bruce Berkowitz

Personal Information
Title Professor
Expertise Retinopathy
Institution Wayne State University
Data Summary
Grants/SubContracts 1
Progress Reports 1
Publications 15
Protocols 0
Committees 1


MRI Phenotyping of Murine Diabetic Retinopathy
Prognostic imaging biomarkers are a powerful non-destructive approach for characterizing pathophysiology linked with retinal complications of type 1 diabetes in both mice and humans. We have already validated a clinically-relevant MRI biomarker, oxygenation response during a provocation (i.e., DeltaP02), as a measure of retinal vascular function. Retinal DeitaP02 is altered before the appearance of microangiopathy in both preclinical and clinical studies, and is prognostic in preclinical studies of drug treatments which correct vascular histopathology. However, it has not yet been possible to use MRI to monitor functional abnormalities in vision-critical non-vascular receptoral (i.e., outer) retina and post-receptoral (inner) retina, which are also a feature of diabetic retinopathy. Our long term goal is to use prognostic MRI biomarkers to quantitatively phenotype vascular and non-vascular retinal dysfunction associated with diabetes. Healthy vision is-linked with proper cellular demand for ions. Perturbed ion homeostasis occurs early in the course of diabetic retinopathy but imaging methods that can simultaneously measure retinal layer thickness and intraretinal ion demand have not yet been available. We have developed a new functional MRI method for measuring non-vascular layer-specific retinal thickness and ion demand during light and dark adaptation in rodents. This new method, manganese-enhanced MRI (MEMRI), takes advantage of the facts that manganese (Mn2+) ion acts as a surrogate for cellular demand for ions, including calcium, and is a strong MRI contrast agent. The availability of an FDA-approved manganese-based contrast agent raises the possibility of future clinical applications of MEMRI. We confirmed that type 1 diabetes-induced MEMRI and DeitaP02 defects in rats are important endpoints because both abnormalities were corrected with alpha-lipoic acid treatment, a drug which inhibits the appearance of vascular histopathology. Our overlying hypothesis is that early in the course of type 1 diabetes, abnormal ion demand in non-vascular retina (as assessed by MEMRI), appears before that of dysfunctional oxygenation response (measured by DeltaP02). Aim 1: To test the prediction that diabetes-induced abnormalities in retinal ion demand are present before perturbations in oxygenation response. At various times after conversion to diabetes, we will compare MEMRI-based structural and functional patterns in inner and outer retina, and retinal DeitaP02 in mouse models of diabetic retinopathy.

Progress Reports

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MRI Phenotyping of Murine Diabetic Retinopathy (Berkowitz, Bruce)
10/31/2008View Progress Report Document

Annual Reports

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Year: 2015; Items: 5

MRI of Rod Cell Compartment-specific Function in Disease and Treatment In Vivo.
Berkowitz BA, Bissig D, Roberts R
Progress in retinal and eye research, 2015
In press
Oxidative stress and light-evoked responses of the posterior segment in a mouse model of diabetic retinopathy.
Berkowitz BA, Grady EM, Khetarpal N, Patel A, Roberts R
Investigative ophthalmology & visual science, 2015 (56), 606 - 15
Catalase Therapy Corrects Oxidative Stress-induced Pathophysiology in Incipient Diabetic Retinopathy.
Giordano C, Roberts R, Krentz K, Bissig D, Talreja D, Kumar A, Terlecky S, Berkowitz BA
Investigative ophthalmology & visual science, 2015
Photoreceptors in diabetic retinopathy.
Kern TS, Berkowitz BA
Journal of diabetes investigation, 2015 (6), 371 - 380
Systemic Retinaldehyde Treatment Corrects Retinal Oxidative Stress, Rod Dysfunction, and Impaired Visual Performance in Diabetic Mice.
Berkowitz BA, Kern TS, Bissig D, Patel P, Bhatia A, Kefalov VJ, Roberts R
Investigative ophthalmology & visual science, 2015 (56), 6294 - 303

Year: 2014; Items: 1

Development of an MRI biomarker sensitive to tetrameric visual arrestin 1 and its reduction via light-evoked translocation in vivo.
Berkowitz BA, Gorgis J, Patel A, Baameur F, Gurevich VV, Craft CM, Kefalov VJ, Roberts R
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2014 (29), 554 - 564

Year: 2013; Items: 1

MRI biomarkers for evaluation of treatment efficacy in preclinical diabetic retinopathy.
Berkowitz BA, Bissig D, Dutczak O, Corbett S, North R, Roberts R
Expert opinion on medical diagnostics, 2013 (7), 393 - 403
Submitted Externally

Year: 2012; Items: 2

Evidence for diffuse central retinal edema in vivo in diabetic male sprague dawley rats.
Berkowitz BA, Bissig D, Ye Y, Valsadia P, Kern TS, Roberts R
PLoS ONE, 2012 (7), e29619
Acute systemic 11-cis-retinal intervention improves abnormal outer retinal ion channel closure in diabetic mice.
Berkowitz BA, Bissig D, Patel P, Bhatia A, Roberts R
Molecular vision, 2012 (18), 372 - 376
Submitted Externally

Year: 2010; Items: 2

Evidence for a critical role of panretinal pathophysiology in experimental ROP.
Berkowitz BA, Roberts R
Documenta ophthalmologica. Advances in ophthalmology, 2010 (120), 13 - 24
Validation of structural and functional lesions of diabetic retinopathy in mice.
Kern TS, Tang J, Berkowitz BA
Molecular vision, 2010 (16), 2121 - 31

Year: 2008; Items: 3

MRI retinovascular studies in humans: research in patients with diabetes.
Trick GL, Edwards PA, Desai U, Morton PE, Latif Z, Berkowitz BA
NMR in biomedicine, 2008 (21), 1003 - 1012
Retinal Ion Regulation in a Mouse Model of Diabetic Retinopathy: Natural History and the Effect of Cu/Zn Superoxide Dismutase Overexpression
Bruce A. Berkowitz, Marius Gradianu, David Bissig, Timothy S. Kern, Robin Roberts
Investigative ophthalmology & visual science, 2008

Year: 2007; Items: 1

Impaired apparent ion demand in experimental diabetic retinopathy: correction by lipoic Acid.
Berkowitz BA, Roberts R, Stemmler A, Luan H, Gradianu M
Investigative ophthalmology & visual science, 2007 (48), 4753 - 4758
Submitted Externally

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No protocols found.

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