Neuroactive Steroids Protect Retinal Tissue through σ1 Receptors

Abstract

The term ‘neuroactive steroids’ has been adopted for steroids, including 17β-oestradiol and dehydroepiandrosteronesulphate (DHEA-S), that might alter neuronal excitability through the cell surface through interaction with specific neurotransmitter receptors. It has been shown [1] that administration of 17β-oestradiol exerts protective effects against ischaemic damage in rat retina. Recently, we demonstrated [2] that 17β-oestradiol and DHEA-S inhibit biochemical changes induced by ischaemia injury in rat retina and that these effects were antagonized by σ1 receptor blocker pre-treatment. More recently, we showed [3] that neuroactive steroids protect retinal pigment epithelium against oxidative stress and that this effect was blocked by pretreatment with σ1 receptor antagonist. The mechanism by which neuroactive steroids exert these protective effects remains unclear. A direct interaction between neuroactive steroids and σ1 receptors has been hypothesized from the finding that several steroids inhibit the binding of σ1 receptor radioligands in vitro and in vivo [4]. σ1 Receptors are a unique class of non-opioid, non-phencyclidine-binding sites heterogeneously distributed in the nervous system and in peripheral organs that may serve as receptors for any, as yet unidentified, endogenous ligand. Recently, the presence of σ1 receptors in rat Muller cells, rat ganglion cells and human retinal pigment epithelial cells have been demonstrated [5], in spite of the functional role of σ1 receptors not yet being clearly determined. The present study was designed to determine whether 17β-oestradiol and DHEA-S protect rat retinal tissue against ischaemia/reperfusion damage and whether σ1 receptors are involved in the mechanism of action.