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. ? ? ?
|Imbert-Fernandez, Yoannis; Radde, Brandie N; Teng, Yun et al. (2011) MUC1/A and MUC1/B splice variants differentially regulate inflammatory cytokine expression. Exp Eye Res 93:649-57|
|Klinge, Carolyn M; Radde, Brandie N; Imbert-Fernandez, Yoannis et al. (2011) Targeting the intracellular MUC1 C-terminal domain inhibits proliferation and estrogen receptor transcriptional activity in lung adenocarcinoma cells. Mol Cancer Ther 10:2062-71|
|Imbert, Yoannis; Foulks, Gary N; Brennan, Mark D et al. (2009) MUC1 and estrogen receptor alpha gene polymorphisms in dry eye patients. Exp Eye Res 88:334-8|