Role of Retinal Microvasculature in Posterior Uveitis

描述（由申请人提供）：后葡萄膜炎是一组异质性的潜在致盲性炎症性疾病，主要累及视网膜和/或脉络膜。虽然后葡萄膜炎的不同亚型已知是自身免疫性的、感染性的和肿瘤性的，但负责这些疾病的基本致病机制仍不清楚。最近认识到，不同的血管床在整个身体的特点是由特定的细胞粘附分子和化学引诱物，我们假设，关键是了解后葡萄膜炎的发病机制，并制定有效的治疗干预措施，是确定独特的一套分子信号表达的视网膜微血管内皮细胞。使用独特的、供体匹配的眼血管内皮细胞培养和cDNA微阵列技术，研究人员将研究视网膜内皮在不同刺激条件下的8,000多个基因的表达，并与虹膜和脉络膜内皮的基因表达进行比较。此外，研究人员将利用两种视网膜内皮细胞“探针”，即弓形虫速殖子，一种优先感染视网膜的原生动物寄生虫的感染形式，以及原发性中枢神经系统淋巴瘤患者的恶性B细胞，这种肿瘤也优先累及视网膜。将采用新的测定法来研究与视网膜血管内皮上的这些微生物和淋巴细胞结合的特异性，并分离它们的潜在受体。预计这些研究将提供有关后葡萄膜炎中白细胞和微生物归巢机制的新信息。这种理解可能会指导后葡萄膜炎的新治疗方法的发展，这些治疗方法针对视网膜微血管内皮细胞与浸润细胞或入侵微生物之间的特定相互作用。这些研究还应该对影响视网膜循环的不相关疾病以及其他身体部位的组织特异性炎症和感染有影响。

DESCRIPTION (provided by applicant): Posterior uveitis is a heterogeneous group of potentially blinding inflammatory disorders that primarily involve the retina and/or choroid. While different subtypes of posterior uveitis are known to be autoimmune, infectious and neoplastic, the basic pathogenic mechanisms responsible for these diseases remain unclear. Consistent with recent recognition that different vascular beds throughout the body are characterized by specific sets of cell adhesion molecules and chemoattractants, we hypothesize that the key to understanding the pathogenesis of posterior uveitis, and to developing effective therapeutic interventions, is defining the unique set of molecular signals expressed by retinal microvascular endothelium. Using unique, donor-matched, ocular vascular endothelial cell cultures and cDNA microarray technology, the investigators will study expression of over 8,000 genes by retinal endothelium, under different conditions of stimulation, and in comparison to gene expression by iris and choroidal endothelium. In addition, the investigators will make use of two retinal endothelial cell "probes", namely, Toxoplasma gondii tachyzoites, infectious forms of a protozoan parasite that preferentially infect the retina, and malignant B cells from patients with primary central nervous system lymphoma, a tumor that also preferentially involves retina. Novel assays will be employed to investigate specificity of binding to, and isolate potential receptors for, these microbes and lymphocytes on retinal vascular endothelium. It is anticipated that these studies will provide new information about the mechanisms that are responsible for homing of leukocytes and microrganisms to the eye in posterior uveitis. This understanding may direct the development of new treatments for posterior uveitis that target specific interactions between the retinal microvascular endothelium and the infiltrating cell or invading microbe. The studies should also have implications for unrelated diseases affecting the retinal circulation, as well as tissue-specific inflammations and infections at other body sites.