Characterisation of 11beta hydroxysteroid dehydrogenase 1 in ocular and orbital tissues

Abstract

The eye is a glucocorticoid target tissue which orchestrates expression of target genes through the glucocorticoid receptor (GR). The classical function of GR involves its interaction with glucocorticoid to influence transcription of genes involved in numerous physiological processes which include inflammation. The first line of defence in the ocular tissues includes the mucosal barrier and expression of receptors that recognise pathogen. These mechanisms activate the innate immune response during inflammation, however, in the ‘normal’ eye, immunomodulatory components exist to promote immune privilege. 11beta hydroxysteroid dehydrogenase 1 (11β-HSD1) regulates cortisol locally in tissues and has already been localised to to some ocular surface and intraocular tissues. The aim of this thesis is to evaluate the functional role of 11β-HSD1 in the eye and the orbit and whether the 11β-HSD1 can be targeted to modify various disease processes in the eye. An animal model was used to characterise the pre-receptor regulation of glucocorticoids and this was further characterised in human ocular and orbital tissues and cells. The results showed that 11β-HSD1 is functional in certain ocular (corneal epithelial, fibroblast and conjunctival fibroblast) and orbital (orbital preadipocyte) cells. The data therefore emphasises the putative role of 11β-HSDs in the ocular and orbital microenvronment.