Hyperoxia-Induced Proliferative Retinopathy: Early Interruption of Retinal Vascular Development with Severe and Irreversible Neurovascular Disruption.
Hyperoxia-Induced Proliferative Retinopathy: Early Interruption of Retinal Vascular Development with Severe and Irreversible Neurovascular Disruption.
复制标题
DOI：
10.1371/journal.pone.0166886
复制
发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Fawzi AA
中科院分区：
文献类型：
--
作者：
Lajko M;Cardona HJ;Taylor JM;Shah RS;Farrow KN;Fawzi AA
支气管肺发育不良（BPD）是早产儿新生儿发病的一个主要原因，是由于肺发育受阻和出生后多次损伤所致。BPD婴儿暴露于补充氧气也有早产儿视网膜病变的风险。因此，我们研究了高氧对BPD小鼠模型视网膜血管的影响。该模型的视网膜表型，我们称之为高氧诱导的增殖性视网膜病变（HIPR），显示出视网膜血管系统的严重破坏和血管图案的丧失、无序的视网膜内血管生成、炎症和视网膜脱离。新生小鼠从出生后第0天（P）至P14天暴露于75%的氧气中以建立BPD模型，然后允许在室内空气中恢复1天（P15）、7天（P21）或14天（P28）。我们定量视网膜厚度、HIF-1α、NOX 2和VEGF的蛋白水平，并通过免疫组织化学检查这些蛋白的细胞定位。我们检查了视网膜血管完整性和炎症标志物，包括巨噬细胞（F4/80）和淋巴细胞（CD 45 R）。与对照组相比，正常的视网膜血管发育被严重破坏，取而代之的是一片混乱的视网膜内血管生成。在所有时间点，与对照组相比，HIPR显示持续的玻璃体血管和显著更薄的中央视网膜。HIF-1α蛋白水平在P15时升高，而VEGF水平持续升高直至P21。在P21时观察到视网膜内纤维蛋白原，随后在P28时观察到视网膜下沉积。在P21和P28分别观察到炎性淋巴细胞和巨噬细胞。该模型呈现出视网膜血管发育中断、视网膜内血管生成炎症和视网膜脱离的严重表型。
Bronchopulmonary dysplasia (BPD) is a major cause of neonatal morbidity in premature infants, occurring as a result of arrested lung development combined with multiple postnatal insults. Infants with BPD exposed to supplemental oxygen are at risk of retinopathy of prematurity as well. Thus, we studied the effects of hyperoxia on the retinal vasculature in a murine model of BPD. The retinal phenotype of this model, which we termed hyperoxia-induced proliferative retinopathy (HIPR), shows severe disruption of retinal vasculature and loss of vascular patterning, disorganized intra-retinal angiogenesis, inflammation and retinal detachment. Neonatal mice were subjected to 75% oxygen exposure from postnatal day (P)0 to P14 to model BPD, then allowed to recover in room air for 1 (P15), 7 (P21), or 14 days (P28). We quantified retinal thickness, protein levels of HIF-1α, NOX2, and VEGF, and examined the cellular locations of these proteins by immunohistochemistry. We examined the retinal blood vessel integrity and inflammatory markers, including macrophages (F4/80) and lymphocytes (CD45R). Compared to controls, normal retinal vascular development was severely disrupted and replaced by a disorganized sheet of intra-retinal angiogenesis in the HIPR mice. At all time-points, HIPR showed persistent hyaloidal vasculature and a significantly thinner central retina compared to controls. HIF-1α protein levels were increased at P15, while VEGF levels continued to increase until P21. Intra-retinal fibrinogen was observed at P21 followed by sub-retinal deposition in at P28. Inflammatory lymphocytes and macrophages were observed at P21 and P28, respectively. This model presents a severe phenotype of disrupted retinal vascular development, intra-retinal angiogenesis inflammation and retinal detachment.
登录
查看更多内容
胎儿生长限制和支气管肺发育不良的早产儿的肺部高血压。
影响因子：
2.9
作者：
Check, J.;Gotteiner, N.;Liu, X.;Su, E.;Porta, N.;Steinhorn, R.;Mestan, K. K.
通讯作者：
Mestan, K. K.
DOI：
10.1152/ajplung.00176.2014
发表时间：
2015-08-15
影响因子：
4.9
作者：
Datta, Ankur;Kim, Gina A.;Berkelhamer, Sara K.
通讯作者：
Berkelhamer, Sara K.
DOI：
10.1164/rccm.200902-0242oc
发表时间：
2009-12-01
影响因子：
24.7
作者：
Aslam, Muhammad;Baveja, Rajiv;Kourembanas, Stella
通讯作者：
Kourembanas, Stella
影响因子：
3.3
作者：
ENG, LF
通讯作者：
ENG, LF
影响因子：
6.2
作者：
Dorrell, Michael I.;Aguilar, Edith;Jacobson, Ruth;Trauger, Sunia A.;Friedlander, Jeffrey;Siuzdak, Gary;Friedlander, Martin
通讯作者：
Friedlander, Martin