High-resolution manganese-enhanced MRI of experimental retinopathy of prematurity.
OBJECTIVE
To test the hypothesis that in experimental retinopathy of prematurity (ROP), retinal neovascularization (NV) and vessel tortuosity have distinct spatial and temporal links with receptor and postreceptor ion demand.


METHODS
Newborn rats were raised in either room air (controls) or variable oxygen (50%/10% [50/10]). After 14 days, 50/10 rats were recovered in room air until postnatal day (P) 19 or P22. Peripheral retinal NV severity and incidence and panretinal arteriole and venule tortuosity indexes (TI(a), TI(v)) were measured from ADPase-stained retinal wholemounts. Intraretinal ion demand and retinal thickness were measured from high-resolution manganese-enhanced MRI (MEMRI). In separate experiments, intraretinal manganese uptake was also measured in adult rats pretreated with diltiazem, a Ca(2+) channel antagonist.


RESULTS
In 50/10 rats, peripheral retinal NV severity was significantly greater than in controls at P19 and was decreased by P22. Panretinal TI(a) and TI(v) were increased over control values at P19, but only TI(v) decreased by P22. Unlike control retinas at P19 that had a centroperipheral total retinal thickness gradient, 50/10 retinas had similar central and peripheral total retinal thickness. The 50/10 group also demonstrated a correlation between peripheral retinal NV and TI(a) and TI(v). Peripheral intraretinal uptake of manganese was significantly supernormal at P19 and decreased by P22. Increased peripheral intraretinal retinal manganese uptake was associated with peripheral NV severity and panretinal TI(a). In contrast, ion demand of central postreceptor, but not receptor, retina was significantly associated with peripheral NV severity and panretinal TI(a). Panretinal TI(v) was not correlated with intraretinal ion demand in any case. In adult rats, diltiazem suppressed (P < 0.05) intraretinal manganese uptake.


CONCLUSIONS
The present data raise the possibility that altered retinal layer-specific ion demand causes retinal circulation abnormalities in experimental ROP.
Berkowitz
Bruce A
BA
Department of Anatomy and Cell Biology, Wayne State University, Detroit, Michigan 48201, USA. baberko@med.wayne.edu
Roberts
Robin
R
Penn
John S
JS
Gradianu
Marius
M
D000818:Animals; D000831:Animals, Newborn; D001081:Apyrase / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008345:Manganese / Q000378:metabolism*; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015861:Retinal Neovascularization / Q000378:metabolism* / Q000503:physiopathology; D012178:Retinopathy of Prematurity / Q000378:metabolism* / Q000503:physiopathology
D002121:Calcium Channel Blockers; D008345:Manganese; D001081:Apyrase; D004110:Diltiazem