Berkowitz Bruce A, Roberts Robin, Penn John S, Gradianu Marius
Department of Anatomy and Cell Biology, Wayne State University, Detroit, Michigan 48201, USA.
Invest Ophthalmol Vis Sci. 2007 Oct;48(10):4733-40. doi: 10.1167/iovs.06-1516.
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.
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.
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.
The present data raise the possibility that altered retinal layer-specific ion demand causes retinal circulation abnormalities in experimental ROP.
验证以下假说：在实验性早产儿视网膜病变（ROP）中，视网膜新生血管形成（NV）和血管迂曲与受体及受体后离子需求存在不同的空间和时间联系。
将新生大鼠饲养于常氧环境（对照组）或可变氧环境（50%/10%[50/10]）。14天后，将50/10组大鼠置于常氧环境中恢复至出生后第（P）19天或P22天。从经腺苷二磷酸酶（ADPase）染色的视网膜铺片中测量周边视网膜NV严重程度、发生率以及全视网膜小动脉和小静脉迂曲指数（TI(a)，TI(v)）。从高分辨率锰增强磁共振成像（MEMRI）测量视网膜内离子需求和视网膜厚度。在单独的实验中，还测量了用钙通道拮抗剂地尔硫卓预处理的成年大鼠的视网膜内锰摄取。
在50/10组大鼠中，周边视网膜NV严重程度在P19时显著高于对照组，并在P22时降低。全视网膜TI(a)和TI(v)在P19时高于对照值，但仅TI(v)在P22时降低。与P19时具有中央到周边总视网膜厚度梯度的对照视网膜不同，50/10组视网膜的中央和周边总视网膜厚度相似。50/10组还显示周边视网膜NV与TI(a)和TI(v)之间存在相关性。周边视网膜内锰摄取在P19时显著超常，并在P22时降低。周边视网膜内锰摄取增加与周边NV严重程度和全视网膜TI(a)相关。相比之下，中央受体后而非受体视网膜的离子需求与周边NV严重程度和全视网膜TI(a)显著相关。在任何情况下，全视网膜TI(v)均与视网膜内离子需求无关。在成年大鼠中，地尔硫卓抑制（P<0.05）视网膜内锰摄取。
目前的数据增加了以下可能性，即视网膜层特异性离子需求改变导致实验性ROP中的视网膜循环异常。
