Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, Australia; Lions Eye Institute, The University of Western Australia, Perth, Australia.
Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, Australia; Lions Eye Institute, The University of Western Australia, Perth, Australia.
Prog Retin Eye Res. 2019 May;70:23-54. doi: 10.1016/j.preteyeres.2019.01.001. Epub 2019 Feb 13.
The central role of the cardiovascular system is to maintain adequate capillary perfusion. The spatially and temporally heterogeneous nature of capillary perfusion has been reported in some organs. However, such heterogeneous perfusion properties have not been sufficiently explored in the retina. Arguably, spatial and temporal heterogeneity of capillary perfusion could be more predominant in the retina than that in other organs. This is because the retina is one of the highest metabolic demand neural tissues yet it has a limited blood supply due to optical requirements. In addition, the unique heterogeneous distribution of retinal neural cells within different layers and regions, and the significant heterogeneity of intraretinal oxygen distribution and consumption add to the complexity. Retinal blood flow distribution must match consumption of nutrients such as oxygen and glucose within the retina at the cellular level in order to effectively maintain cell survival and function. Sophisticated local blood flow control in the microcirculation is likely required to control the retinal capillary perfusion to supply local retinal tissue and accommodate temporal and spatial variations in metabolic supply and demand. The authors would like to update the knowledge of the retinal microvessel and capillary network and retinal oxidative metabolism from their own studies and the work of others. The coupling between blood supply and energy demands in the retina is particularly interesting. We will mostly describe information regarding the retinal microvessel network and retinal oxidative metabolism relevant to the spatial and temporal heterogeneity of capillary perfusion. We believe that there is significant and necessary spatial and temporal heterogeneity and active regulation of retinal blood flow in the retina, particularly in the macular region. Recently, retinal optical coherence tomography angiography (OCTA) has been widely used in ophthalmology, both experimentally and clinically. OCTA could be a valuable tool for examining retinal microvessel and capillary network structurally and has potential for determining retinal capillary perfusion and its control. We have demonstrated spatial and temporal heterogeneity of capillary perfusion in the retina both experimentally and clinically. We have also found close relationships between the smallest arterioles and capillaries within paired arterioles and venules and determined the distribution of smooth muscle cell contraction proteins in these vessels. Spatial and temporal heterogeneity of retinal capillary perfusion could be a useful parameter to determine retinal microvessel regulatory capability as an early assay for retinal vascular diseases. This topic will be of great interest, not only for the eye but also other organs. The retina could be the best model for such investigations. Unlike cerebral vessels, retinal vessels can be seen even at the capillary level. The purpose of this manuscript is to share our current understanding with the readers and encourage more researchers and clinicians to investigate this field. We begin by reviewing the general principles of microcirculation properties and the spatial and temporal heterogeneity of the capillary perfusion in other organs, before considering the special requirements of the retina. The local heterogeneity of oxygen supply and demand in the retina and the need to have a limited and well-regulated retinal circulation to preserve the transparency of the retina is discussed. We then consider how such a delicate balance of metabolic supply and consumption is achieved. Finally we discuss how new imaging methodologies such as optical coherence tomography angiography may be able to detect the presence of spatial and temporal heterogeneity of capillary perfusion in a clinical setting. We also provide some new information of the control role of very small arterioles in the modulation of retinal capillary perfusion which could be an interesting topic for further investigation.
心血管系统的核心作用是维持足够的毛细血管灌注。已有研究报道,一些器官的毛细血管灌注具有时空异质性。然而,这种异质灌注特性在视网膜中尚未得到充分探索。可以说,与其他器官相比,视网膜中的毛细血管灌注的时空异质性可能更为突出。这是因为视网膜是代谢需求最高的神经组织之一,但由于光学要求,其血液供应有限。此外,视网膜神经细胞在不同层和区域的独特异质分布,以及视网膜内氧分布和消耗的显著异质性,增加了其复杂性。为了有效地维持细胞存活和功能,视网膜内的营养物质(如氧气和葡萄糖)的消耗与毛细血管的血流分布必须在细胞水平上相匹配。在微循环中进行精细的局部血流控制,可能有助于控制视网膜毛细血管灌注,以供应局部视网膜组织,并适应代谢供应和需求的时空变化。作者希望从自己的研究和他人的工作中更新对视网膜微血管和毛细血管网络以及视网膜氧化代谢的认识。血液供应与视网膜能量需求之间的耦合尤其有趣。我们将主要描述与毛细血管时空异质性和视网膜氧化代谢相关的信息。我们认为,在视网膜中,特别是在黄斑区域,存在显著且必要的时空异质性和视网膜血流的主动调节。最近,视网膜光学相干断层扫描血管造影(OCTA)在眼科的实验和临床中得到了广泛应用。OCTA 可能是一种用于检查视网膜微血管和毛细血管网络结构的有价值的工具,并且有可能确定视网膜毛细血管灌注及其控制。我们已经在实验和临床中证明了视网膜中的毛细血管灌注具有时空异质性。我们还发现了配对的小动脉和小静脉中的最小动脉和毛细血管之间的密切关系,并确定了这些血管中平滑肌收缩蛋白的分布。视网膜毛细血管灌注的时空异质性可能是确定视网膜微血管调节能力的有用参数,作为视网膜血管疾病的早期检测指标。这个话题不仅对眼睛,而且对其他器官都将非常有趣。视网膜可能是进行此类研究的最佳模型。与脑血管不同,视网膜血管甚至在毛细血管水平也可以看到。本文的目的是与读者分享我们目前的认识,并鼓励更多的研究人员和临床医生来研究这一领域。我们首先回顾了其他器官中微循环特性和毛细血管时空异质性的一般原则,然后考虑了视网膜的特殊要求。讨论了视网膜内氧供应和需求的局部异质性以及需要有限且良好调节的视网膜循环来保持视网膜的透明性。然后我们考虑了如何实现这种代谢供应和消耗的微妙平衡。最后,我们讨论了像 OCTA 这样的新成像方法如何能够在临床环境中检测到毛细血管时空异质性的存在。我们还提供了一些关于非常小的动脉在调节视网膜毛细血管灌注中的控制作用的新信息,这可能是一个有趣的进一步研究课题。