Androgen Control of Human Corneal Epithelial Cells Payal Khandelwal and David A. Sullivan Schepens Eye Research Institute and Harvard Medical School, Boston, MA The authors have no financial interest in the subject matter of this poster.

 Androgens have been reported to correct defects, facilitate wound healing, suppress angiogenesis and stimulate mitosis in the corneal epithelium.  We hypothesize that these hormone actions involve the regulation of gene expression, and tested this hypothesis in the current study. Purpose:

 Primary human corneal epithelial cells were treated with dihydrotestosterone (DHT) or placebo and then processed for the analysis of gene expression with Illumina humanHT-12 v3 expression BeadChips and BeadStudio and Geospiza software. Methods:

 DHT significantly influenced the expression of over 1,500 genes in primary human corneal epithelial cells.  For example, androgen exposure upregulated genes encoding S100 calcium binding protein P (modulates tumorigenesis and cell cycle progression), syntenin (regulates transmembrane receptor trafficking, tumour cell metastasis, neuronal synapse function and NF-kappaB activation pathways), decorin (inhibits angiogenesis) and vimentin (helps maintain cell integrity) [Table 1]. Results:

Glutaredoxin Kallikrein related peptidases 12 and 6 Matrix metallopeptidase 10 S100 Calcium binding protein P SynteninDecorinVimentin Small proline rich protein 2E Transcobalamin 1 Interleukin 1 family, member 9 Dual specificity phosphatase 9 Table 1: List of some of the genes upregulated in primary human corneal epithelial cells by androgen exposure

Results:  Androgen exposure suppressed genes producing tubulins (promote angiogenesis), thrombospondin1 (influence angiogenesis and tumorigenesis), keratin 3 (involved with corneal dystrophy) and matrix metallopeptidase 9 (degrades collagens) [Table 2].  DHT treatment also exerted a significant impact on many ontologies, including oxidative phosphorylation, transmembrane ion transport and cellular localization.

Keratins 3, 27, 6a Tubulins β 2A, α 1B, α 1A, α 4A, α 1C, β 2C TransgelinEnvoplakin Thrombospondin 1 Cadherin Matrix metallopeptidase 9 Septin 4 Cyclin D1 Actin β Agrin Table 2: List of some of the genes downregulated in primary human corneal epithelial cells by androgen exposure

Conclusion:  DHT regulates the expression of numerous genes which may play a role in corneal health and disease. Analysis of these genes and ontologies may provide insights into the mechanism(s) of androgen action on the corneal epithelium.