Ionic dysregulatory phenotyping of pathologic retinal thinning with manganese-enhanced MRI.
OBJECTIVE
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 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.


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 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.
Berkowitz
Bruce A
BA
Department of Anatomy and Cell Biology, Wayne State University, Detroit, Michigan 48201, USA. baberko@med.wayne.edu
Gradianu
Marius
M
Schafer
Stephen
S
Jin
Ying
Y
Porchia
Andre
A
Iezzi
Raymond
R
Roberts
Robin
R
D000818:Animals; D002712:Chlorides / Q000008:administration & dosage; D005260:Female; D000860:Hypoxia / Q000150:complications; D007089:Image Enhancement; D007274:Injections, Intraperitoneal; D007477:Ions / Q000378:metabolism*; D019194:Ischemic Preconditioning; D008279:Magnetic Resonance Imaging; D008297:Male; D008345:Manganese; D017895:Manganese Compounds / Q000008:administration & dosage; D010641:Phenotype; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012162:Retinal Degeneration / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D012171:Retinal Vessels; D012680:Sensitivity and Specificity
D002712:Chlorides; D007477:Ions; D017895:Manganese Compounds; D008345:Manganese; C025340:manganese chloride