PHYSIOLOGY OF RETINAL PERICYTES

描述（改编自申请人摘要）： 目的是描述的机制，其中的功能， 视网膜周细胞在病理生理条件下发生改变。 包被微血管的周细胞是我们感兴趣的 因为它们似乎调节视网膜内的血液流动， 毛细血管。同样令人感兴趣的是， 周细胞是糖尿病最早的组织病理学发现之一， 视网膜病变该项目的一个前提是， 微环境调节周细胞的生理。的 调查人员已经把重点放在了 血-视网膜屏障，因为这种屏障的缺陷通常发生在 严重威胁视力的疾病，如糖尿病。研究 该策略基于这样的前提，即离子通道在以下方面起着至关重要的作用： 周细胞功能研究人员假定， 当血浆来源的分子 从血管系统的血视网膜屏障 已经暴露了为了解决这些问题，他们开发了一个 膜片钳技术用于 分析位于微- 从人和动物视网膜新鲜分离的血管。初步 研究中，他们发现等离子体激活了几种类型的离子 视网膜周细胞中的通道。澄清各种机制， 来自血管系统的分子调节周细胞的功能， 该项目将实现以下具体目标。(1)表征 当视网膜周细胞被激活时，其活性改变的离子通道 暴露于血浆;（2）检验胰岛素样生长 因子（IGF-1）是一种血浆衍生的分子，其调节 视网膜周细胞离子通道功能的研究;（3）检测视网膜周细胞离子通道的功能。 假设离子通道的激活是由等离子体衍生的 分子，如IGF-1，是密切相关的增加， 周细胞内的钙浓度。从长远来看， 了解周细胞对病理反应的机制， 生理条件将有助于制定治疗策略 维持视网膜周细胞的功能和存活 糖尿病视网膜病变等疾病。

DESCRIPTION (Adapted from applicant's abstract): The long-range objective is to characterize the mechanisms by which the function of retinal pericytes is altered under pathophysiological conditions. Pericytes, the cells which ensheathe the microvessels, are of interest since they appear to regulate the flow of blood within retinal capillaries. Also of interest is the fact that the selective loss of pericytes is one of the first histopathological findings in diabetic retinopathy. A premise of the project is that molecules in the microenvironment regulate the physiology of the pericyte. The investigators have focused on the consequences of a breakdown in the blood-retinal barrier since defects in this barrier occur commonly in important sight-threatening disorders such as diabetes. The research strategy is based on the premise that ion channels play a vital role in pericyte function. The investigators postulate that the activity of ion channels expressed by pericytes is altered when plasma-derived molecules leak from the vascular system at sites where the blood-retinal barrier is compromised. To address these issues, they have developed an experimental preparation in which the patch-clamp technique is used to analyze the activity of ion channels in pericytes located on micro- vessels freshly isolated from human and animal retinas. In preliminary studies, they discovered that plasma activates several types of ion channels in retinal pericytes. To clarify the mechanisms by which molecules from the vascular system regulate the function of pericytes, this project will address the following specific aims. (1) characterize the ion channels whose activities are altered when retinal pericytes are exposed to plasma; (2) test the hypothesis that insulin-like growth factor (IGF-1) is one of the plasma-derived molecules which regulates the function of ion channels in retinal pericytes; and (3) test the hypothesis that the activation of ion channels by plasma-derived molecules, such as IGF-1, is closely associated with an increase in the concentration of calcium within the pericyte. Over the long term, understanding the mechanisms by which pericytes respond to patho- physiological conditions will help in devising therapeutic strategies for maintaining the function and survival of pericytes in retinal disorders such as diabetic retinopathy.