ENDOGENOUS LECTINS OF THE RETINAL PIGMENT EPITHELIUM

与其他组织中的疾病过程一样，疾病过程涉及 RPE通常以粘合剂合同的变化为特征， 不受控制的增殖，或细胞识别机制的缺陷。 这些基本过程并不是相互排斥的，而且通常 在功能上相关。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， 或者是凝集素。因此，凝集素在细胞识别、增殖、 和粘附性是目前许多领域研究的热点 细胞和分子生物学。因此，重要的职能角色具有 在不同的生理过程中发现了凝集素 配子相互作用、肝功能和炎症。凝集素可能是 细胞表面的变化对视网膜功能也很重要 碳水化合物识别系统与几个眼科疾病有关 精神错乱。然而，从文献上看，相对来说， 人们对内源性视网膜凝集素知之甚少。我们有 最近从人的培养物中纯化了两个半乳糖结合蛋白 RPE细胞，初步鉴定为PEL-70和PEL-210/47。 初步证据表明，半乳糖识别系统 至少涉及这些分子中的一个可能在 调节RPE细胞的增殖，这是疾病的一个关键特征，如 增殖性玻璃体视网膜病变。我们的目标是了解 PEL蛋白参与这一功能和其他细胞功能，并与 这种知识对眼睛中的疾病过程有影响。为了实现这一目标， 我们建议使用免疫学方法来确定时间和地点 无论是在正常情况下还是在其他情况下，细胞内都有PEL的表达。 我们将研究PEL作为细胞识别和/或黏附的潜力 分子，并作为细胞迁移和增殖的调节器。 最后，我们将从化学和酶的角度对PEL分子进行剖析 识别功能域的方法。从建议中获得的知识 研究可以帮助我们理解、发现并有望纠正 未来RPE细胞的行为令人担忧。

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.