Ion and fluid transport mechanisms within the eye are important for several key physiological processes including the maintenance of corneal transparency and the regulation of intraocular pressure (IOP). The mechanism involved in epithelial sodium transport in the eye is regulated by corticosteroids and at a pre-receptor level, by 11β-hydroxysteroid dehydrogenase (11β-HSD) activity. Recent studies localised type 1 (11β-HSD1), an oxo-reductase that activates cortisol from cortisone, to the non-pigmented layer (NPE) of the human ocular ciliary body (CB) epithelium and corneal epithelium (CE). Its potential role in aqueous humour (AH) production provides a novel target for AH suppression and treatment of IOP.
Animal models are essential for further evaluation of 11β-HSD1 activity within the eye and the New Zealand White Albino rabbit (NZWAR) has been widely used to study IOP and a variety of ocular diseases. In-house generated primary antibodies to human 11β-HSD1 were used to study 11β-HSD1 expression within NZWAR eye sections and cells. Specific enzyme assays were also performed to assess 11β-HSD1 activity in this animal model.
Immunohistochemical studies showed that, as in human tissue, 11β-HSD1 localised to the NPE of the CB and the CE. Additionally, specific activity assays indicated predominant oxo-reductase activity compared to dehydrogenase activity in CB tissue (median, 44.4±16% conversion vs 18.6±12% conversion; P=0.003, n=12) and primary CE cells (oxo-reductase; median, 3.0±1.9 pmol/mg/h, vs dehydrogenase, 0.5±0.8 pmol/mg/h; P=0.006, n=12). Further confirmation of 11β-HSD1 expression was obtained by Western blot analysis of CB tissue and immunocytochemistry of primary cultured CE cells.
The results obtained indicate the NZWAR is a suitable in-vivo model for further investigation of 11β-HSD1 activity in the regulation of IOP and corneal physiology. This will help establish the NZWAR as a suitable model for the evaluation of specific topical 11β-HSD1 inhibitors for the treatment of raised intraocular pressure-related disorders.
01 - 05 Apr 2006
European Society of Endocrinology