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糖尿病性毛细血管闭塞的进展:一种模型

Progression of Diabetic Capillary Occlusion: A Model.

作者信息

Fu Xiao, Gens John Scott, Glazier James A, Burns Stephen A, Gast Thomas J

机构信息

The Biocomplexity Institute, Indiana University, Bloomington, Indiana, United States of America.

Department of Physics, Indiana University, Bloomington, Indiana, United States of America.

出版信息

PLoS Comput Biol. 2016 Jun 14;12(6):e1004932. doi: 10.1371/journal.pcbi.1004932. eCollection 2016 Jun.

Abstract

An explanatory computational model is developed of the contiguous areas of retinal capillary loss which play a large role in diabetic maculapathy and diabetic retinal neovascularization. Strictly random leukocyte mediated capillary occlusion cannot explain the occurrence of large contiguous areas of retinal ischemia. Therefore occlusion of an individual capillary must increase the probability of occlusion of surrounding capillaries. A retinal perifoveal vascular sector as well as a peripheral retinal capillary network and a deleted hexagonal capillary network are modelled using Compucell3D. The perifoveal modelling produces a pattern of spreading capillary loss with associated macular edema. In the peripheral network, spreading ischemia results from the progressive loss of the ladder capillaries which connect peripheral arterioles and venules. System blood flow was elevated in the macular model before a later reduction in flow in cases with progression of capillary occlusions. Simulations differing only in initial vascular network structures but with identical dynamics for oxygen, growth factors and vascular occlusions, replicate key clinical observations of ischemia and macular edema in the posterior pole and ischemia in the retinal periphery. The simulation results also seem consistent with quantitative data on macular blood flow and qualitative data on venous oxygenation. One computational model applied to distinct capillary networks in different retinal regions yielded results comparable to clinical observations in those regions.

摘要

开发了一种解释性计算模型,用于研究视网膜毛细血管丢失的连续区域,这些区域在糖尿病性黄斑病变和糖尿病性视网膜新生血管形成中起很大作用。严格随机的白细胞介导的毛细血管闭塞无法解释大片连续视网膜缺血区域的发生。因此,单个毛细血管的闭塞必然会增加周围毛细血管闭塞的可能性。使用Compucell3D对视网膜中央凹周围血管扇区以及周边视网膜毛细血管网络和缺失的六边形毛细血管网络进行建模。中央凹周围的建模产生了毛细血管丢失扩展的模式以及相关的黄斑水肿。在周边网络中,扩展的缺血是由连接周边小动脉和小静脉的梯形毛细血管逐渐丢失所致。在毛细血管闭塞进展的情况下,黄斑模型中的系统血流在后期血流减少之前会升高。仅初始血管网络结构不同但氧气、生长因子和血管闭塞动力学相同的模拟,重现了后极部缺血和黄斑水肿以及视网膜周边缺血的关键临床观察结果。模拟结果似乎也与黄斑血流的定量数据和静脉氧合的定性数据一致。一个应用于不同视网膜区域不同毛细血管网络的计算模型产生了与这些区域临床观察结果相当的结果。

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