Minority Predoctoral Fellowship Program

描述（由申请人提供）：干眼病是由于泪液缺乏或泪液蒸发过多，导致眼表炎症和损伤。粘蛋白是高度O-糖基化的蛋白质，其润滑和保护眼表面。最近的研究结果表明，粘蛋白MUC 1具有抗炎特性，也可以与雌激素受体-α相互作用，从而调节基因转录。雄激素是维持眼表稳态的关键。MUC 1和雄激素受体（AR）之间的潜在相互作用可以提供额外的保护：我的长期目标是阐明干眼症发病机制中涉及的分子机制。我的假设是MUC 1和雄激素受体（AR）是可以共同作用以保护眼表的关键因素。该假设将通过三个具体目标进行检验：目标1-确定人眼表面上皮细胞系中MUC 1和AR之间的相互作用;目标2-阐明MUC 1和AR在这些细胞中的抗炎作用;以及目标3-我们发现表达MUC 1/A剪接变体而不是MUC 1/B的人对干眼症较不敏感。我们将确定MUC 1/A和MUC 1/B剪接变异体的信号转导能力是否不同。

DESCRIPTION (provided by applicant): Dry eye disease is due to tear deficiency or excessive tear evaporation and results in inflammation and damage to the ocular surface. Mucins are highly O-glycosylated proteins that lubricate and protect the ocular surface. Recent findings indicate that the mucin MUC1 has anti-inflammatory properties and also can interact with estrogen receptor-alpha thereby modulating gene transcription. Androgens are key to maintaining homeostasis of the ocular surface. A potential interaction between MUC1 and androgen receptor (AR) could confer additional protection: My long term goal is to elucidate the molecular mechanisms involved in the pathogenesis of dry eye. My hypothesis is that MUC1 and androgen receptor (AR) are key factors that can act together to protect the ocular surface. The hypothesis will be tested by three specific aims: Aim 1- Determine the interaction between MUC1 and AR in human ocular surface epithelial cell lines; Aim 2- Elucidate the anti-inflammatory role of MUC1 and AR in those cells; and Aim 3- We have found that persons expressing the MUC1/A splice variant rather than MUC1/B are less susceptible to dry eye. We will determine if MUC1/A and MUC1/B splice variants differ in their signal transduction capabilities.