Dynamics of angiogenesis during murine retinal development: a coupled in vivo and in silico study.
Dynamics of angiogenesis during murine retinal development: a coupled in vivo and in silico study.
复制标题
小鼠视网膜发育过程中血管生成的动态：体内和计算机耦合研究。
DOI：
10.1098/rsif.2012.0067
复制
发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Watson MG
中科院分区：
文献类型：
--
作者：
Watson MG
新生野生型小鼠视网膜浅血管丛(RVP)的发育方式已有较好的文献记载，并对数学模型界提出了一个有趣的挑战。出生前，星形胶质细胞在视神经头边缘开始萌发和增殖，随后星形胶质细胞在血小板衍生生长因子(PDGF)-A的趋化梯度作用下迁移，导致视网膜内表面形成致密的支架。星形胶质细胞表达多种趋化和趋化蛋白，这些蛋白随后诱导内皮细胞发芽并调节RVP的生长。根据实验信息，建立了一个二维混合偏微分方程-离散模型来跟踪单个星形胶质细胞和内皮细胞在适当的生化信号作用下向外迁移的情况。血液灌流包括整个神经丛的发育过程，进化中的视网膜树可以通过几种生物刺激来适应和重塑。将得到的野生型SilicoRVP结构与在不同发育阶段获得的相应实验整体支架进行比较，发现各自的血管形态之间的一致性很好。随后的数值预测有助于阐明视网膜发育的一些关键生物学过程，并展示虚拟视网膜在研究各种眼部血管相关疾病方面的潜力。
The manner in which the superficial retinal vascular plexus (RVP) develops in neonatal wild-type mice is relatively well documented and poses an interesting challenge to the mathematical modelling community. Prior to birth, astrocyte sprouting and proliferation begin around the edge of the optic nerve head, and subsequent astrocyte migration in response to a chemotactic gradient of platelet-derived growth factor (PDGF)-A results in the formation of a dense scaffold on the surface of the inner retina. Astrocytes express a variety of chemotactic and haptotactic proteins that subsequently induce endothelial cell sprouting and modulate growth of the RVP. An experimentally informed, two-dimensional hybrid partial differential equation-discrete model is derived to track the outward migration of individual astrocyte and endothelial tip cells in response to the appropriate biochemical cues. Blood perfusion is included throughout the development of the plexus, and the evolving retinal trees are allowed to adapt and remodel by means of several biological stimuli. The resulting wild-typein silicoRVP structures are compared with corresponding experimental whole mounts taken at various stages of development, and agreement between the respective vascular morphologies is found to be excellent. Subsequent numerical predictions help elucidate some of the key biological processes underlying retinal development and demonstrate the potential of the virtual retina for the investigation of various vascular-related diseases of the eye.