Minority Predoctoral Fellowship Program

描述(申请人提供)：干眼症是由于泪液缺乏或泪液蒸发过多而导致眼表发炎和损伤。粘蛋白是一种高度O-糖基化的蛋白质，可以润滑和保护眼睛表面。最近的研究表明，粘蛋白MUC1具有抗炎作用，还可以与雌激素受体-α相互作用，从而调节基因转录。雄激素是维持眼表动态平衡的关键。MUC1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发病的分子机制。我的假设是，MUC1和雄激素受体(AR)是共同作用保护眼表的关键因素。这一假设将通过三个具体的目标来检验：目标1--确定MUC1和AR在人类眼表上皮细胞系中的相互作用；目标2-阐明MUC1和AR在这些细胞中的抗炎作用；以及目标3-我们发现表达MUC1/A剪接变体的人不太容易患干眼。我们将确定MUC1/A和MUC1/B剪接变体在信号转导能力上是否有所不同。

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.