Glucocorticoid Receptor Signaling is Critical for Mouse Corneal Development, Inhibition of Inflammatory Response and Neovascularization of the Cornea

Synthetic glucocorticoids are widely prescribed in the treatment of ocular infections and disorders. The actions of glucocorticoids are mediated by the glucocorticoid receptor (GR); however, the molecular and physiological functions of GR signaling in the cornea are poorly understood. To understand the direct role of GR signaling in the cornea, we developed mice with conditional knockout of GR in the corneal epithelium. Global transcriptomic approaches revealed that loss of GR signaling in the cornea resulted in the dysregulation of a large cohort of genes strongly associated with an enhanced immune response. To generate mice lacking GR in the cornea epithelium (corneaGRKO mice), mice homozygous for the floxed GR allele (GRflox) were crossed with mice expressing Cre recombinase driven by the P0 promoter of Pax6 gene. Male corneaGRKO mice that were 3 months of age and their age-matched control (GRflox) littermates were euthanized, eyes removed, and total RNA was isolated from the whole cornea. The control GRflox and corneaGRKO groups each had 4 replicates, where each replicate had 4-6 corneas pooled into one sample. Indexed samples were sequenced using the 75bp pair-end protocol using the Illumina NextSeq500 sequencer as per the manufacturer’s protocol. Reads greater than 40 million reads per sample were aligned to the reference genome UCSC mm9.