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 眼睛、肾脏和心脏的床。 在糖尿病视网膜病变中，视网膜 微血管通透性增加，基底增厚 膜和经常失去周细胞。 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 微血管结构的可检测变化和视力障碍， 可能是糖尿病视网膜病变的主要生理缺陷之一。 目前的血管渗漏理论解释了流量增加， 通过增加表面积的血管内压力，或通过直接 内皮屏障通透性的变化。 在体外系统中，我们先前已经表明，在不改变 压力或表面积，内皮细胞单层后，其渗透性 对autocoids和激素的反应特征。 的目标 该建议是开发一种体外模型系统， 确定视网膜微血管屏障是如何维持的， 屏障在糖尿病视网膜病变中受损。 我们首先提出， 开发一种视网膜血管模型， 在多孔微载体珠上培养的毛细血管内皮细胞， 灌注在色谱细胞柱中。 该模型设计允许 灵敏地检测视网膜内皮渗透性的变化。 其次，我们建议将此屏障的特性与 内皮屏障由来自其他器官的内皮细胞形成。 和 第三，我们将研究三种独特的视网膜/糖尿病 环境因素，可能会影响这一障碍的显着 从以前的调查增加渗透性相关 患有糖尿病视网膜病变，在我们的初步结果中，我们描述了， 据我们所知，第一次测量的渗透性的 体外视网膜毛细血管内皮屏障。 确定导致冲突的具体调解人和机制 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管理。

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.