Local Retinal Vasoregulatory Mechanisms

描述（由申请人提供）：视网膜血管疾病是美国失明和视力障碍的重要原因。眼科研究的证据表明，异常血流调节和/或血管舒缩功能导致的组织缺血引发或促成了许多眼部疾病的发病机制。间接证据表明，血流的自动调节发生在视网膜血管系统中;然而，控制视网膜血流的潜在机制尚不清楚。我们的长期目标是改善与视网膜血流调节受损有关的视网膜疾病的预防和治疗。为了达到这一目标，需要对视网膜微血管的基本血管扩张行为有基本的了解。在这项研究建议中，设计了一个综合计划来表征局部血管调节现象（即，肌源性和流量依赖性反应），并研究这两种反应在视网膜小动脉网络中的单个微血管水平上的相互作用。所提出的研究的中心假设是视网膜小动脉以大小依赖性方式对压力刺激作出积极响应（即，生肌反应）和流动（即，剪切应力诱导的血管舒张）。实验将在猪视网膜小动脉的各种分支顺序中进行，使用分离的插管血管技术，以允许独立控制压力和流量。将确定血管调节中涉及的内皮和细胞通路的作用。Lih Kuo教授是本次K 08奖的导师，他之前建立了这种用于冠状动脉微血管研究的新型孤立血管技术。在他的监督下，候选人获得了支持所提出假设的初步数据。我们的期望是，这些实验的结果将提供新的见解，在视网膜微循环中的局部血管调节机制，并最终允许开发新的策略，以预防和治疗与微血管功能障碍相关的视网膜疾病。此外，该K 08奖将为主要研究者提供受保护的时间，以获得他成为眼血管研究领域独立研究者所必需的专业知识和知识。

DESCRIPTION (provided by applicant): Retinal vascular diseases are a significant cause of blindness and visual impairment in the United States. Evidence from ophthalmic research suggests that tissue ischemia resulting from abnormal blood flow regulation and/or vasomotor function initiates or contributes to the pathogenesis of many ocular diseases. Indirect evidence indicates that autoregulation of blood flow occurs in the retinal vasculature; however, the underlying mechanisms that control retinal blood flow are not known. Our long-term objective is to improve the prevention and therapy of retinal diseases that are linked to impaired blood flow regulation in the retina. To reach this goal, a fundamental understanding of basic vasomotor behavior of retinal microvasculature is required. In this research proposal, an integrative plan was designed to characterize the local vasoregulation phenomena (i.e., myogenic and flow-dependent responses) in retinal arterioles and to study the interaction of these two responses at the single microvessel level in the retinal arteriolar network. The central hypothesis for the proposed research is that retinal arterioles actively respond, in a size-dependent manner, to stimulation by pressure (i.e., myogenic response) and flow (i.e., shear stress-induced vasodilation). The experiments will be performed in various branching orders of porcine retinal arterioles using isolated, cannulated vessel techniques to allow pressure and flow to be independently controlled. The role of endothelium and cellular pathways involved in vasoregulation will be determined. Professor Lih Kuo, the mentor for this K08 Award, previously established this novel isolated vessel technique for the study of coronary microvessels. Under his supervision, the candidate has obtained preliminary data that support the proposed hypothesis. Our expectation is that the results of these experiments will provide new insights into the local vasomotor regulatory mechanisms in the retinal microcirculation and ultimately allow for the development of new strategies to prevent and treat retinal diseases associated with microvascular dysfunction. In addition, this K08 Award will allow for protected time for the principal investigator to acquire the expertise and knowledge which are essential to his becoming an independent investigator in the area of ophthalmic vascular research.