REGULATION OF RETINAL MICROVESSEL PERMEABILITY IN VITRO

糖尿病前期/糖尿病状态在功能上改变了微血管 眼、肾、心的床。在糖尿病视网膜病变中，视网膜 微血管通透性增加，基底膜增厚 细胞膜，并经常丢失周细胞。两国之间的关系 这些屏障成分的变化和渗透性的变化 不清楚。视网膜微血管通透性增加通常先于 微血管结构和视力损害的可检测的变化和 可能是糖尿病视网膜病变的中枢生理缺陷之一。 目前的血管泄漏理论也解释了流量的增加 通过增加表面积的血管内压或直接 内皮屏障通透性的变化。 在体外系统中，我们之前已经证明，在没有改变的情况下 压力或表面积，内皮细胞单层后来的通透性 对自体激素和荷尔蒙有反应的特点。的目标是 这项建议是开发一个体外模型系统，用于 确定视网膜微血管屏障如何维持以及如何维持 糖尿病视网膜病变中屏障受损。我们首先提出了 建立一种视网膜血管系统模型，该模型由视网膜 毛细血管内皮细胞在多孔微载体上的培养 在色谱柱中灌流。这种型号的设计允许 灵敏地检测视网膜内皮细胞通透性的变化。 其次，我们建议将这一屏障的属性与 来自其他器官的内皮细胞形成的内皮屏障。和 第三，我们将检查三种独特的视网膜/糖尿病的影响 可能显著影响这一障碍的环境因素 根据先前对相关渗透性增加的调查 糖尿病视网膜病变，我们在初步结果中描述了， 据我们所知，第一次测量的渗透率 体外培养的视网膜毛细血管内皮细胞屏障。 确定导致以下问题的特定调解人和机制 糖尿病视网膜微血管屏障的丧失可能有助于改善 糖尿病引起的眼部并发症的处理。

The prediabetic/diabetic condition functionally alters the microvascular bed of the eye, kidney and heart. In diabetic retinopathy, retinal microvessels have increase permeability, exhibit thickened basement membranes and frequently lose pericytes. The relationship between changes in these barrier components and changes in permeability remains unclear. Increased retinal microvessel permeability often precedes detectable alterations in microvessel structure and vision impairment and may be one of the central physiological defects in diabetic retinopathy. Current theories of vascular leak account for an increase in flux either by an increase intravascular pressure of surface area, or by direct changes in the permeability of the endothelial barrier. In an vitro systems, we have shown previously that, without changes in pressure or surface area, endothelial monolayers later their permeability characteristic in response to autocoids and hormones. The objective of this proposal is to develop an in vitro models system useful for determining how retinal microvessel barrier is maintained and how this barrier is compromised in diabetic retinopathy. We first proposed to develop a model of the retinal vasculature consisting of retinal capillary endothelial cells cultured on porous microcarriers beads and perfused in chromatographic cell-columns. This model design permits sensitive detection of changes in retinal endothelial permeability. Secondly, we propose to compare the properties of this barrier to endothelia barrier formed by endothelia cells from other organs. And thirdly, we will examine the effects of three unique retinal/diabetic environmental factors that may influence this barrier's significantly from previous investigations of the increased permeability associated with diabetic retinopathy, and in our preliminary results we describe, to our knowledge, the first measurements of the permeability of the retinal capillary endothelial barrier in vitro. Identification of the specific mediators and mechanisms which lead to the loss of retinal microvascular barrier in diabetes may help to improve the management of ocular complications stemming from diabetes.