LACRIMAL GLAND BIOINFORMATICS: A NEURAL CONNECTION OF DRY EYE AND AGING

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 泪腺组织对良好的视力至关重要。它是泪液中蛋白质和液体的主要贡献者，有助于维持角膜的光学表面，保护角膜免受病原体的侵害，并维持眼表的细胞结构。泪腺分泌的激活受神经控制。角膜的感觉（传入）神经支配是激活包括中枢和外周自主通路的分泌运动回路的主要神经输入。完整的神经回路对于泪腺结构和功能的维持也是至关重要的。该建议的假设是，随着年龄的增长，这种神经相互作用逐渐下降，特别是角膜感觉下降，影响泪腺功能。我们知道，通过去神经支配去除神经相互作用导致泪腺的结构和功能改变，并导致干眼症。一些提示来自基因表达谱研究，其揭示了与内质网和分泌器相关的基因表达的减少以及与炎症和免疫调节剂相关的基因表达的增加。拟议的研究将寻求确定这些基因表达模式及其转录调控的年龄特异性变化。我们将测试泪腺的基因反应作为年龄的函数，角膜创伤和药理学挑战，以确定基因表达谱的变化。我们将利用基因表现资料发展泪腺特定生物资讯网路服务。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The lacrimal gland tissue is of critical importance to good vision. It is the major contributor of proteins and fluid in tears that help to maintain the optical surface of the cornea, to protect the cornea from pathogens, and to maintain the cellular structure of the ocular surface. Activation of lacrimal gland secretion is under neural control. Sensory (afferent) innervation of the cornea is the primary neural input which activates a secretomotor circuit comprising central and peripheral autonomic pathways. The intact neural circuit is also critical for the maintenance of lacrimal gland structure and function. The hypothesis of the proposal is a progressive decline in this neural interaction with age, particularly the decreased corneal sensation, affecting lacrimal gland function. We know that removal of the neural interaction by denervation resulted in structural and functional alteration to the lacrimal gland, and contributes to dry eye disease. Some hints come from gene expression profiling studies which revealed a reduction in the expression of genes relating to the endoplasmic reticulum and secretory apparatus and an increased in expression of genes associated with inflammation and immune regulators. The proposed studies will seek to identify age-specific changes in these patterns of gene expression and theirs transcriptional regulation. We will test the gene response of the lacrimal gland as a function of age by corneal wounding and pharmacologic challenge to determine changes in gene expression profiles. We will utilize the gene expression data to develop a lacrimal gland specific bioinformatics web service.