Abstract
Purpose: :
The regulation of the intracellular calcium concentration is important for a number of functional processes in retinal neurons as well as for the control of neuronal survival after exposure to extrinsic or intrinsic damage. Intracellular calcium channels release calcium from intracellular stores, and participate in calcium-mediated neuronal functions through mechanisms such as calcium induced calcium release. Their activity can be controlled by numerous signaling pathways including endogenously produced steroid hormones that contribute to neuronal function but also play a role in neuroprotection. The present study determined the effect of estrogen / 17β-estradiol on intracellular calcium channels, their function and cellular activity in mouse retina neurons. The goal of the study was to determine mechanisms of action connecting non-genomic steroid hormone and calcium signaling in the retina, which has the potential to identify new therapeutic strategies in treating neurodegenerative diseases of the retina.
Methods: :
Adult mouse retinal neurons were isolated and exposed to 17β-estradiol. The effect on intracellular calcium signaling and kinase signaling pathways was determined with immunochemistry, calcium imaging and single channel electrophysiology.
Results: :
Intracellular calcium channels were regulated by non-genomic actions of intracellular estrogen signaling and activation of neuro-protective kinase signaling pathways was determined at both the cellular and molecular level. 17β-estradiol modulates both the activity of intracellular calcium channels and kinases with kinases being activated by 17β-estradiol also modulating intracellular calcium channels.
Conclusions: :
The present study suggests that gonadal steroid hormones control intracellular calcium signaling and neuro-protective kinase signaling pathways in retinal neurons. Control of both pathways plays a potential role in identifying novel protective strategies and therapeutic interventions for degenerative diseases affecting retinal neurons.
Keywords: neuroprotection • calcium • phosphorylation