The Role of Selectin-Mediated Recognition in Glaucoma

选择素介导的识别在青光眼中的作用

• 批准号: 6927190
• 负责人: Noorjahan Panjwani
• 金额: $ 16.35万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6927190
• 关键词: carbohydrate receptor; cell adhesion; clinical research; extracellular matrix; glaucoma; glycoproteins; human old age (65+); human subject; human tissue; immunocytochemistry; pathologic process; receptor binding; selectins; trabecular meshwork; western blottings

DESCRIPTION (provided by applicant): Glaucoma is the second leading cause of blindness in the world after cataract, affecting approximately 70 million people. Elevated intraocular pressure due to the obstruction of the aqueous outflow pathway is a major causal risk factor in the development of primary open-angle glaucoma. Treatment of this blinding disease is compromised because of the lack of understanding of the molecular mechanism responsible for the resistance to the outflow facility. In a recent study, a carbohydrate-binding protein, E-selectin (ELAM-1, CD62E), was identified as a specific molecular marker of glaucoma. It was demonstrated that while E-selectin is consistently present on trabecular meshwork (TM) cells in the outflow pathways of eyes of glaucomas of diverse etiology, it was absent in the outflow pathway of all normal eyes examined. We propose a unique hypothesis that TM cell surface E-selectin, by binding to its putative glycoprotein counterreceptors on adjacent cells or in aqueous humor activates key signaling pathways, which in turn, by promoting cell-matrix and/or cell-to-cell interactions and cytoskeletal changes, provide a protective stress response specific to the aqueous outflow pathway of the eye. In this NEI R03 application, we propose pilot studies to determine whether the hypothesis merits a detailed investigation. In Aim 1, using immunohistochemical and Western blot analysis, we shall establish which specific carbohydrate ligands of selectins, if any, are expressed on the TM cells and in the aqueous humor of normal and glaucomatous eyes. In Aim 2, we shall determine whether the selectins/carbohydrate-mediated signaling promotes adhesion of TM cells to a variety of extracellular matrix molecules in vitro. The proposed studies will determine whether the selectin-based carbohydrate recognition system plays a role in the pathogenic mechanisms of aqueous outflow resistance in glaucoma.

描述（由申请人提供）：青光眼是世界上仅次于白内障的第二大失明原因，影响大约 7000 万人。 由于房水流出通路阻塞而导致的眼压升高是原发性开角型青光眼发生的主要危险因素。 由于缺乏对流出设施抵抗力的分子机制的了解，这种致盲疾病的治疗受到影响。 在最近的一项研究中，碳水化合物结合蛋白 E-选择素（ELAM-1、CD62E）被确定为青光眼的特异性分子标记。 结果表明，虽然 E-选择素始终存在于不同病因青光眼眼睛流出通路中的小梁网 (TM) 细胞上，但在所有检查的正常眼睛的流出通路中均不存在 E-选择素。 We propose a unique hypothesis that TM cell surface E-selectin, by binding to its putative glycoprotein counterreceptors on adjacent cells or in aqueous humor activates key signaling pathways, which in turn, by promoting cell-matrix and/or cell-to-cell interactions and cytoskeletal changes, provide a protective stress response specific to the aqueous outflow pathway of the eye. 在此 NEI R03 申请中，我们提出了试点研究，以确定该假设是否值得进行详细调查。 在目标 1 中，我们将使用免疫组织化学和蛋白质印迹分析来确定选择素的哪些特定碳水化合物配体（如果有的话）在 TM 细胞以及正常眼和青光眼眼的房水中表达。 在目标 2 中，我们将确定选择素/碳水化合物介导的信号传导是否在体外促进 TM 细胞与各种细胞外基质分子的粘附。 拟议的研究将确定基于选择素的碳水化合物识别系统是否在青光眼房水流出阻力的致病机制中发挥作用。