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High-Resolution Manganese-Enhanced MRI of Experimental Retinopathy of Prematurity

¹From the Department of Anatomy and Cell Biology and the ²Department of Ophthalmology, Wayne State University, Detroit, Michigan; and the ³Vanderbilt Eye Institute, Vanderbilt University School of Medicine, Nashville, Tennessee.

PURPOSE. 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 Ca²⁺ 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.

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