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Published on: July 22, 2014
Ionic dysregulatory phenotyping of pathologic retinal thinning with manganese-enhanced MRI
Bruce A Berkowitz1, Marius Gradianu, Stephen Schafer
1Department of Anatomy and Cell Biology, Wayne State University, Detroit, Michigan 48201, USA. baberko@med.wayne.edu
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 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.
Insights
Manganese-enhanced MRI (MEMRI) detects ionic changes in retinal thinning, aiding early diagnosis of neurodegenerative diseases. This noninvasive technique shows promise for monitoring treatment effectiveness.
Area of Science:
- Neuroscience
- Ophthalmology
- Medical Imaging
Background:
- Retinal thinning is linked to ionic dysregulation.
- Current diagnostic methods may lack sensitivity for early detection.
Purpose of the Study:
- To evaluate manganese-enhanced MRI (MEMRI) as a sensitive measure of retinal ionic dysregulation in pathologic retinal thinning.
- To test MEMRI's robustness in detecting specific ionic phenotypes.
Main Methods:
- High-resolution MEMRI was performed on rats at different developmental and degeneration stages after MnCl2 injection.
- Retinal thickness and intraretinal ion activity were measured.
- Histology confirmed retinal damage; ischemia/reperfusion models were also used.
Main Results:
- MEMRI detected significant changes in intraretinal ion regulation in neurodegenerative models before and during pathologic retinal thinning.
- These ionic changes were not observed during normal development.
- A neuroprotective preconditioning protocol altered the observed ionic phenotype.
Conclusions:
- MEMRI offers a noninvasive, objective method to measure ionic dysregulation in the retina.
- This technique can potentially improve early diagnosis and treatment prognosis for neurodegenerative diseases affecting the retina.
