Department of Mathematical Sciences, Indiana University-Purdue University Indianapolis, 402 N. Blackford St, LD 270, Indianapolis, IN 46202, USA.
Department of Mathematics and Statistics, Metropolitan State University of Denver, P.O. Box 173362, Campus Box 38, Denver, CO 80217, USA.
Math Biosci. 2023 Mar;357:108969. doi: 10.1016/j.mbs.2023.108969. Epub 2023 Jan 23.
The retinal vascular network supplies perfusion to vital visual structures, including retinal ganglion cells responsible for vision. Impairments in retinal blood flow and oxygenation are involved in the progression of many ocular diseases, including glaucoma. In this study, an established theoretical hybrid model of a retinal microvascular network is extended to include the effects of local blood flow regulation on oxygenation. A heterogeneous representation of the arterioles based on confocal microscopy images is combined with a compartmental description of the downstream capillaries and venules. A Green's function method is used to simulate oxygen transport in the arterioles, and a Krogh cylinder model is applied to the capillary and venular compartments. Acute blood flow regulation is simulated in response to changes in pressure, shear stress, and metabolism. Model results predict that both increased intraocular pressure and impairment of blood flow regulation can cause decreased tissue oxygenation, indicating that both mechanisms represent factors that could lead to impaired oxygenation characteristic of ocular disease. Results also indicate that the metabolic response mechanism reduces the fraction of poorly oxygenated tissue but that the pressure- and shear stress-dependent response mechanisms may hinder the vascular response to changes in oxygenation. Importantly, the heterogeneity of the vascular network demonstrates that traditionally reported average values of tissue oxygen levels hide significant localized defects in tissue oxygenation that may be involved in disease processes, including glaucoma. Ultimately, the model framework presented in this study will facilitate future comparisons to sectorial-specific clinical data to better assess the role of impaired blood flow regulation in ocular disease.
视网膜血管网络为包括负责视觉的视网膜神经节细胞在内的重要视觉结构提供灌注。视网膜血流和氧合的损伤与许多眼部疾病的进展有关，包括青光眼。在这项研究中，建立了一个视网膜微血管网络的理论混合模型，该模型扩展到包括局部血流调节对氧合的影响。基于共聚焦显微镜图像的动脉的异质表示与下游毛细血管和小静脉的隔室描述相结合。使用格林函数方法模拟动脉中的氧气传输，并且应用克罗格圆柱模型应用于毛细血管和小静脉隔室。模拟急性血流调节以响应压力、剪切应力和代谢的变化。模型结果表明，眼内压升高和血流调节受损都会导致组织氧合减少，这表明这两种机制都代表了可能导致眼部疾病特征性氧合受损的因素。结果还表明，代谢反应机制减少了组织中氧气不足的部分，但压力和剪切应力依赖性反应机制可能会阻碍血管对氧合变化的反应。重要的是，血管网络的异质性表明，传统上报告的组织氧水平的平均值掩盖了组织氧合的明显局部缺陷，这些缺陷可能与包括青光眼在内的疾病过程有关。最终，本研究提出的模型框架将有助于未来与特定扇区的临床数据进行比较，以更好地评估血流调节受损在眼部疾病中的作用。
