Ionic Dysregulatory Phenotyping of Pathologic Retinal Thinning with Manganese-Enhanced MRI

Abstract

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. Four hours after intraperitoneal MnCl(2) 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. 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. MEMRI and a nontoxic systemic dose of MnCl(2) 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.