Department of Ophthalmology & Visual Sciences, University of Michigan, Ann Arbor, MI 48105, USA.
Prog Retin Eye Res. 2012 May;31(3):258-70. doi: 10.1016/j.preteyeres.2012.01.001. Epub 2012 Feb 5.
An important challenge in visual neuroscience is to understand the physiology and pathophysiology of the intra-retinal vasculature, whose function is required for ophthalmoception by humans and most other mammals. In the quest to learn more about this highly specialized portion of the circulatory system, a newly developed method for isolating vast microvascular complexes from the rodent retina has opened the way for using techniques such as patch-clamping, fluorescence imaging and time-lapse photography to elucidate the functional organization of a capillary network and its pre-capillary arteriole. For example, the ability to obtain dual perforated-patch recordings from well-defined sites within an isolated microvascular complex permitted the first characterization of the electrotonic architecture of a capillary/arteriole unit. This analysis revealed that this operational unit is not simply a homogenous synctium, but has a complex functional organization that is dynamically modulated by extracellular signals such as angiotensin II. Another recent discovery is that a capillary and its pre-capillary arteriole have distinct physiological differences; capillaries have an abundance of ATP-sensitive potassium (K(ATP)) channels and a dearth of voltage-dependent calcium channels (VDCCs) while the converse is true for arterioles. In addition, voltage transmission between abluminal cells and the endothelium is more efficient in the capillaries. Thus, the capillary network is well-equipped to generate and transmit voltages, and the pre-capillary arteriole is well-adapted to transduce a capillary-generated voltage into a change in abluminal cell calcium and thereby, a vasomotor response. Use of microvessels isolated from the diabetic retina has led to new insights concerning retinal vascular pathophysiology. For example, soon after the onset of diabetes, the efficacy of voltage transmission through the endothelium is diminished; arteriolar VDCCs are inhibited, and there is increased vulnerability to purinergic vasotoxicity, which is a newly identified pathobiological mechanism. Other recent studies reveal that K(ATP) channels not only have an essential physiological role in generating vasomotor responses, but their activation substantially boosts the lethality of hypoxia. Thus, the pathophysiology of the retinal microvasculature is closely linked with its physiology.
视觉神经科学的一个重要挑战是理解视网膜内血管的生理学和病理生理学，人类和大多数其他哺乳动物的视觉感知都需要其功能。为了更多地了解这个循环系统的高度专业化部分，一种新开发的从啮齿动物视网膜中分离出大量微血管复合物的方法为使用膜片钳技术、荧光成像和延时摄影等技术阐明毛细血管网络及其前毛细血管小动脉的功能组织开辟了道路。例如，能够从分离的微血管复合物中的明确定位点获得双穿孔贴片记录，使人们首次能够对毛细血管/小动脉单元的电紧张结构进行特征描述。该分析表明，这个操作单元不是简单的同质合胞体，而是具有复杂的功能组织，其被血管紧张素 II 等细胞外信号动态调节。另一个最近的发现是，毛细血管及其前毛细血管小动脉具有明显的生理差异；毛细血管富含三磷酸腺苷敏感性钾（K(ATP)）通道，电压依赖性钙通道（VDCC）缺乏，而小动脉则相反。此外，在基底细胞和内皮细胞之间，电压传递在毛细血管中更为有效。因此，毛细血管网络具有产生和传递电压的能力，而前毛细血管小动脉则非常适合将毛细血管产生的电压转化为基底细胞钙的变化，从而引起血管运动反应。使用从糖尿病视网膜中分离的微血管进行研究，使人们对视网膜血管病理生理学有了新的认识。例如，在糖尿病发病初期，通过内皮细胞的电压传递效率降低；小动脉的 VDCC 受到抑制，对嘌呤能血管毒性的易感性增加，这是新发现的病理生物学机制。最近的其他研究表明，K(ATP) 通道不仅在产生血管运动反应方面具有重要的生理学作用，而且其激活还大大增加了缺氧的致命性。因此，视网膜微血管的病理生理学与其生理学密切相关。
