ENDOGENOUS LECTINS OF THE RETINAL PIGMENT EPITHELIUM

与其他组织中的疾病过程一样， RPE的特征通常在于粘合剂收缩的变化， 不受调节的增殖或细胞识别机制的缺陷。 这些基本过程并不是相互排斥的，而且往往是相互关联的。 功能相关。 这些细胞活动的一个共同特征是 它们通常涉及碳水化合物结合蛋白的活性， 或凝集素。 因此，凝集素在细胞识别，增殖， 和粘附是目前在许多领域中积极研究的焦点， 细胞和分子生物学 因此，重要的职能作用 在多种生理过程中， 配子相互作用肝功能和炎症 凝集素可能是 对视网膜功能也很重要， 碳水化合物识别系统与几种眼部疾病有关， 紊乱 然而，从文献中可以看出， 对内源性视网膜凝集素的具体了解很少。 我们有 最近从人的培养物中纯化了两种半乳糖结合蛋白， RPE细胞，暂时鉴定为PEL-70和PEL-210/47。 初步证据表明半乳糖识别系统 涉及这些分子中的至少一种分子可能在 调节RPE细胞增殖，这是诸如视网膜色素上皮细胞增生的疾病的关键特征， 增生性玻璃体视网膜病变 我们的目标是了解 PEL蛋白参与了这一和其他细胞功能，并与 这些知识在眼睛中的疾病过程。 为了实现这一目标， 我们建议使用免疫学方法来确定何时何地 在正常条件和其他条件下，PEL在细胞中表达。 我们将研究PELs作为细胞识别和/或粘附的潜力， 分子，并作为细胞迁移和增殖的调节剂。 最后，我们将通过化学和酶的方法对PEL分子进行剖析， 识别功能域的方法。 从拟议方案中获得的知识 研究可以帮助我们理解，检测，并希望纠正 异常的RPE细胞行为。

As with disease processes in other tissues, disease processes involving the RPE often are characterized by changes in adhesive contracts, unregulated proliferation, or a defect in cell recognition mechanisms. These basic processes are not mutually exclusive, and are often functionally related. A common feature of these cellular activities is that they often involve the activity of carbohydrate binding proteins, or lectins. Thus, roles for lectins in cell recognition, proliferation, and adhesion are currently the focus of vigorous study in many fields of cell and molecular biology. As a result, important functional roles have been identified for lectins in such diverse physiological processes as gamete interaction, hepatic function, and inflammation. Lectins may be important for retinal function as well, as changes in cell surface carbohydrate recognition systems have been implicated in several ocular disorders. However, it would appear from the literature that relatively little is known specifically about endogenous retinal lectins. We have recently purified two galactose-binding proteins from cultures of human RPE cells, which are tentatively identified as PEL-70 and PEL-210/47. Preliminary evidence suggests that a galactosyl recognition system involving at least one of these molecules may play a role in the regulation of RPE cell proliferation, a key feature of disorders such as proliferative vitreoretinopathy. It is our goal to understand how the PEL proteins are involved in this and other cell functions, and to relate this knowledge to the disease process in the eye. To achieve this goal, we propose to use immunological approaches to determine when and where PELs are expressed in the cell, under normal conditions and otherwise. We will examine the potential of PELs as cell recognition and/or adhesion molecules, and as regulators of cell migration and proliferation. Finally, we will dissect the PEL molecules by chemical and enzymatic means to identify functional domains. Knowledge gained from the proposed research may help us to understand, detect, and hopefully correct abberant RPE cell behavior in the future.