Limited hyperoxia-induced proliferative retinopathy: A model of persistent retinal vascular dysfunction, preretinal fibrosis and hyaloidal vascular reprogramming for retinal rescue.
Limited hyperoxia-induced proliferative retinopathy: A model of persistent retinal vascular dysfunction, preretinal fibrosis and hyaloidal vascular reprogramming for retinal rescue.
复制标题
DOI：
10.1371/journal.pone.0267576
复制
发表时间：
2022
期刊：
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
早产儿视网膜病变（ROP）仍然是儿童失明的主要原因。有限的高氧诱导的增殖性视网膜病变（L-HIPR）最近被引入作为一个潜在的动物模型的ROP和持久的胎儿血管，但是，详细的病理变化仍然不清楚。为了建立L-HIPR模型，我们将C57 BL/6 J小鼠从出生到出生后第7天（P7）置于65%氧气中。我们在P12和P30之间的时间间隔检查眼睛。在不同的时间点，在分别用苏木精和伊红（H&E）和Masson三色染色的组织切片上定量视网膜形态测量、厚度和视网膜前纤维化。血管发育，血管生成，炎症，和周细胞的覆盖率进行了分析，使用免疫组织化学染色在视网膜平片和横截面。在L-HIPR中，玻璃体血管持续到本研究的最后一个时间点P30，并从P12开始内陷周边视网膜，然后是中央视网膜。从P17开始观察到中央视网膜变形，而周边视网膜从P12到P30表现出变薄的趋势。我们发现L-HIPR与视网膜血管发育延迟和异常相关，随后伴有视网膜炎症、周细胞丢失和视网膜前纤维化。我们的研究提出了一个详细的分析L-HIPR动物模型，证明玻璃体视网膜的病理变化，视网膜前纤维化和持续玻璃体血管到成年。基于我们的研究结果，我们认为玻璃体血管的持续存在和特殊的逐步迁移到视网膜可能提供了一个潜在的拯救机制，值得进一步研究。
Retinopathy of prematurity (ROP) remains the leading cause for blindness in children. Limited hyperoxia induced proliferative retinopathy (L-HIPR) was recently introduced as a potential animal model for ROP and persistent fetal vasculature; however, the detailed pathological changes remain unclear. To model L-HIPR, we placed C57BL/6J mice in 65% oxygen from birth to post-natal day 7 (P7). We examined eyes at intervals between P12 and P30. Retinal morphometry, thickness, and preretinal fibrosis were quantified at different time points on histological sections stained with hematoxylin and eosin (H&E) and Masson Trichrome, respectively. Vascular development, angiogenesis, inflammation, and pericyte coverage were analyzed using immunohistochemistry staining in retinal flat mounts and cross sections. In L-HIPR, the hyaloidal vessels persisted until the latest time point in this study, P30 and began to invaginate the peripheral then central retina starting at P12. Central retinal distortion was noted beginning at P17, while the peripheral retina demonstrated a trend of thinning from P12 to P30. We found that L-HIPR was associated with delayed and abnormal retinal vascular development with subsequent retinal inflammation, pericyte loss and preretinal fibrosis. Our study presents a detailed analysis of the L-HIPR animal model demonstrating vitreoretinal pathologic changes, preretinal fibrosis and persistent hyaloidal vessels into adulthood. Based on our findings, we suggest that the persistence and peculiar stepwise migration of the hyaloidal vessels into the retina may provide a potential rescue mechanism for inner retinal development that deserves further study.
登录
查看更多内容
DOI：
10.1084/jem.20151966
发表时间：
2016-06-27
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Yoshikawa Y;Yamada T;Tai-Nagara I;Okabe K;Kitagawa Y;Ema M;Kubota Y
通讯作者：
Kubota Y
影响因子：
3.7
作者：
Lajko M;Cardona HJ;Taylor JM;Shah RS;Farrow KN;Fawzi AA
通讯作者：
Fawzi AA
影响因子：
3.7
作者：
Nakamura S;Imai S;Ogishima H;Tsuruma K;Shimazawa M;Hara H
通讯作者：
Hara H
DOI：
10.1056/nejmra1208129
发表时间：
2012-12-27
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hartnett ME;Penn JS
通讯作者：
Penn JS
影响因子：
4.4
作者：
Chou, Jonathan C.;Rollins, Stuart D.;Fawzi, Amani A.
通讯作者：
Fawzi, Amani A.