The zinc‐metallothionein redox system in human retina and RPE

Purpose The retina contains the highest concentration of zinc in the human eye and it is primarily associated with the photoreceptors and the RPE. Metallothioneins (MTs) are the main cytosolic zinc‐ion‐binding proteins, and their main roles include neuroprotection and maintenance of cellular zinc homeostasis. Zinc is the main regulator of MTs, and there is a tight control in the number of atoms of zinc bound to the MT proteins (stoichiometry), which could be related with their antioxidant and neuroprotective functions. The main purpose of this work is to study the Zn‐MT system in the RPE and retina of the human eye. Methods We first determined the total content of Zn by elemental mass spectrometry (i.e., ICP‐MS), in RPE and retina from post mortem human donors, and compared its quantitative distribution by bio‐imaging (i.e, laser ablation‐ICP‐MS), on cryogenic eye sections. Secondly, we carried out the quantitative speciation of zinc in the water‐soluble protein fractions of RPE and neural retina, to study its protein binding profile. Finally we studied the effects of metals (i.e., ZnSO4), inflammatory cytokines (i.e., IL1a) and glucocorticoids (i.e., dexamethasone), by ICP‐MS, in an in vitro cellular model of human RPE cells (HRPEsv). Results We found preferential quantitative distribution of zinc in the RPE, followed by the retina in lesser levels. Zinc is mainly associated to high and low molecular mass proteins in both RPE and retina. Exogenous zinc, interleukin and dexamethasone increased MT proteins synthesis and induced a stoichiometric change in MT proteins in HRPEsv cells. Conclusions The stoichiometric transition on Zn‐MT proteins in HRPEsv and its potential implication against oxidative stress processes will be discussed.