CONTACT LENS EFFECTS ON HUMAN OCULAR MUCIN

这个项目的目标是继续我的发展作为一个独立的 科学家和教师。 为了实现这一目标，一个为期五年的博士后 我提出了一个培训计划，将补充我在以下方面的经验： 临床角膜研究，基础科学的高级培训 眼表生物化学，分子生物学， 微生物学和细菌致病机理。 该计划将包括 课程、研讨会和实验室经验 加州、旧金山弗朗西斯科（UCSF）和伯克利（UCB）。 UCSF和UCB 在分子和细胞领域的研究项目中， 生物学，生物化学和化学，以及几个关键的教师将服务 作为赞助商。 拟议中的研究项目经过精心设计 以补充和加强在开发过程中获得的技能， 期间，并将为我提供必要的专业知识，以分析 各种眼表疾病的发病机制。 眼粘蛋白具有 已被证明可以通过抑制 铜绿假单胞菌粘附于眼表。 的目的 这个项目是为了测试隐形透镜的佩戴改变了 眼粘蛋白的量或组成，从而干扰 细菌与泪膜糖蛋白的结合。这一过程的初始阶段 该项目将研究水凝胶接触透镜配戴对 分泌的眼粘蛋白的数量和组成。 粘蛋白样本 将通过冲洗人眼表面获得，并且最佳的 将确定用于纯化粘液糖蛋白技术。 的 分泌的粘蛋白的量和粘蛋白RNA水平将在 接触透镜配戴者与对照组，以及眼内 粘蛋白将使用凝集素和特异性外切糖苷酶进行评估。 的 第二阶段的实验将研究相互作用的性质 铜绿假单胞菌和眼粘蛋白之间，使用竞争性抑制 研究，并将确定是否接触透镜磨损影响 这种互动。 威胁视力的角膜溃疡的风险 过度使用水凝胶镜片导致的严重的公共健康问题 关注，这个项目将分析是否改变眼 粘蛋白有助于这种风险。 了解接触的影响 透镜对眼粘蛋白的磨损可能有助于设计预防 或减少溃疡性角膜炎的风险。这项计划和研究 经验将整合我的临床和基础科学训练， 使我能够对临床观察到的现象提出假设 基于对基础眼部生物学的深刻理解。

The goal of this project is to continue my development as an independent scientist and teacher. To achieve this goal, a five-year postdoctoral training program is proposed that will supplement my experience in clinical corneal research, with advanced training in the basic science disciplines of ocular surface biochemistry, molecular biology, microbiology, and bacterial pathogenesis. The program will include courses, seminars and laboratory experience at the Universities of California, San Francisco (UCSF) and Berkeley (UCB). Both UCSF and UCB document incredibly strong research programs in molecular and cell biology, biochemistry, and chemistry, and several key faculty will serve as sponsors. The proposed research project has been carefully designed to complement and enhance those skills obtained during the development period and will provide me with the necessary expertise to analyze the pathogenesis of various ocular surface diseases. Ocular mucins have been shown to protect against corneal infection by inhibiting Pseudomonas aeruginosa adherence to the ocular surface. The purpose of this project is to test the hypothesis that contact lens wear alters the quantity or composition of ocular mucins and thereby interferes with bacterial binding to tear film glycoproteins. The initial phase of this project will investigate the effects of hydrogel contact lens wear on the quantity and composition of secreted ocular mucins. Mucin samples will be obtained by irrigating the human ocular surface, and the optimal technique for purifying mucous glycoproteins will be determined. The quantity of secreted mucin and mucin RNA levels will be compared in contact lens wearers versus controls, and the composition of ocular mucin will be assessed using lectins and specific exoglycosidases. The second phase of experiments will examine the nature of the interaction between P. aeruginosa and ocular mucins, using competitive inhibition studies, and will determine whether or not contact lens wear affects this interaction. The risk of sight-threatening corneal ulceration resulting from overuse of hydrogel lenses is a significant public health concern, and this project will analyze whether or not changes to ocular mucin contribute to this risk. Understanding the effects of contact lens wear on ocular mucin may aid in the design of strategies to prevent or lessen the risk of ulcerative keratitis. This program and research experience will integrate my clinical and basic science training and enable me to formulate hypotheses about clinically observed phenomenon based upon a firm understanding of fundamental ocular biology.