IOVS Archives of Disease in Childhood
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Originally published In Press as doi:10.1167/iovs.08-1720 on March 24, 2008
 (Investigative Ophthalmology and Visual Science. 2008;49:3178-3184.)
© 2008 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.08-1720
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Ionic Dysregulatory Phenotyping of Pathologic Retinal Thinning with Manganese-Enhanced MRI

Bruce A. Berkowitz,1,2 Marius Gradianu,1 Stephen Schafer,1 Ying Jin,1 Andre Porchia,1 Raymond Iezzi,2 and Robin Roberts1

1From the Departments of Anatomy and Cell Biology and 2Ophthalmology, Wayne State University, Detroit, Michigan.

PURPOSE. To test the hypothesis that manganese-enhanced MRI (MEMRI) provides a sensitive and robust measure of an important retinal ionic dysregulatory phenotype in pathologic retinal thinning.

METHODS. Four hours after intraperitoneal MnCl2 injection, high-resolution MEMRI data were collected from overnight dark-adapted male control Sprague–Dawley and albino Royal College of Surgeons rats before (at development stage postnatal day [P] 17) and during photoreceptor degeneration (P36 and P57). In separate experiments, control rats, with and without repetitive hypoxic preconditioning, were subjected to high IOP (100 mm Hg) for 60 minutes followed by 24 hours or 7 days of reperfusion (e.g., ischemia/reperfusion). Central retinal thickness and intraretinal ion activity were measured from the MEMRI data. Histology examination was also performed to confirm retinal damage.

RESULTS. In two different neurodegenerative models, MEMRI revealed first-time evidence for changes (P < 0.05) in intraretinal ion regulation before and during pathologic, but not (P > 0.05) developmental, retinal thinning. This phenotype was significantly altered by a neuroprotective repetitive hypoxic preconditioning protocol.

CONCLUSIONS. MEMRI and a nontoxic systemic dose of MnCl2 provided an objective, noninvasive measure of an ionic deregulatory phenotype that appears useful for improved early diagnosis and treatment prognosis in a range of neurodegenerative diseases and their treatment.






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