A Time Course Microarray Study of Gene Expression in the Mouse Lacrimal Gland after Acute Corneal Trauma

Abstract

To investigate the effect of corneal trauma on gene expression in the lacrimal gland and to assess how many genes and what specific genes are regulated in response to corneal trauma. A mouse model with acute corneal trauma was created with a chemical burn to the cornea with silver nitrate. Sixty-four female BALB/c mice at 12 weeks of age were randomly divided into eight groups, eight mice per group. The corneas of four mice in each group were bilaterally cauterized with silver nitrate, and another four time-matched mice were used as the control. The total RNA of the lacrimal gland was then extracted, at eight time points--0.5, 1, 3, 8, 24, 72, 120, and 360 hours--after the corneal burn, and gene expression was examined with using cDNA microarray technology. Evaluation of 15,065 genes with multiple array replications showed significantly altered expression in 3,799 genes at one or more of the eight time points. Of those, 1,528 were known genes and 2,271 were unknown. The analysis of known genes showed broad and long-lasting gene suppression in most functional gene groups, including housekeeping, energy metabolism, protein degradation, DNA and protein synthesis, and apoptosis-associated genes. Heat shock genes were upregulated beginning at the 8-hour time point, indicating a stress response. This study demonstrates that corneal trauma has profound effects on the regulation of gene expression in the lacrimal gland and may provide genetic evidence for a cornea-to-lacrimal gland feedback mechanism in dry eye.