Desmin ensheathment ratio as an indicator of vessel stability - Evidence in normal development and in retinopathy of prematurity
Desmin ensheathment ratio as an indicator of vessel stability - Evidence in normal development and in retinopathy of prematurity
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DOI：
10.1016/s0002-9440(10)63389-5
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发表时间：
2004-10-01
影响因子：
6
通讯作者：
Hughes, S
中科院分区：
文献类型：
--
作者：
Chan-Ling, T;Page, MP;Hughes, S
我们开发了一种衡量周细胞/内皮相互作用的指标，结蛋白包膜比率(DER)，使用中间丝结蛋白作为周细胞包膜的指标，并在正常视网膜血管发育和早产儿猫视网膜病变(ROP)模型中检测了DER。我们还研究了壁细胞在ROP发病机制中的作用。出生后第1天对45只幼猫视网膜进行结蛋白、α-平滑肌肌动蛋白(SIMA)和异凝素-B4的标记。新生的小猫暴露在高氧中，然后回到室内空气中0到40天(DRA)，也被贴上了类似的标签。在共聚焦图像上，结蛋白与凝集素标记的比率产生了DER。超微结构研究表明，即使在最原始的血管上也存在壁细胞。在正常发育期间，未成熟的维管束床的DER为0.3~0.6，而成熟的维管束床以出生后第28天为主，其DER更大。P<0.9。未成熟的周细胞和平滑肌细胞不能阻止高氧诱导的血管退行性变。P在ROP的血管增生期，视网膜内和视网膜前血管的DER在0.2到0.5之间。在恢复期，DER随着病理的消退而增加，在34DRA时达到0.9。出生后第五周DER的稳定与先前报道的小猫对高氧诱导的血管退化的抵抗力的发展在时间上是一致的。这些观察结果表明，DER为0.9代表血管稳定性阈值，ROP期间观察到的低DER可能增加了壁细胞异常在ROP发病机制中发挥关键作用的可能性。
We developed a measure of pericyte/endothelial interaction, the desmin ensheathment ratio (DER), using the intermediate filament desmin as an indicator of pericyte ensheathment and have examined the DER in normal retinal vascular development and in the kitten retinopathy of prematurity (ROP) model. We also examined the role of mural cells in the pathogenesis of ROP. Postnatal day It to 45 kitten retinae were labeled for desmin, a-smooth muscle actin (SIMA), and isolectin-B4. Newborn kittens exposed to hyperoxia and then returned to room air for 0 to 40 days (dRA) were similarly labeled. The ratio of desmin to lectin labeling on confocal images yielded the DER. Ultrastructural studies showed that mural cells were present on even the most primitive vessels. During normal development, immature vascular beds had DERs of 0.3 to 0.6 whereas mature beds, which predominated by postnatal day 28, had DERs greater. p than 0.9. Immature pericytes and smooth muscle cells did not prevent by hyperoxia-induced vessel regression.. p During the vasoproliferative stage of ROP, the DERs of intra- and preretinal vessels ranged between 0.2 and 0.5. In the recovery stage, the DER increased in parallel with regression of pathology, reaching 0.9 at 34 dRA. Stabilization of the DER by the fifth postnatal week was temporally coincident with the development of resistance to hyperoxia-induced vessel regression previously reported in the kitten. These observations lead us to suggest that a DER of 0.9 represents a vascular stability threshold and that a low DER observed during ROP raises the possibility that mural cell abnormalities play a key role in the pathogenesis of ROP.