OUABAIN INDUCES M2 MICROGLIAL POLARIZATION IN RAT RETINAL CELL CULTURES: AN EFFECT MEDIATED BY IL-4

Retina belongs to the central nervous system (SNC) and its development includes a programmed cell death (PCD) period. Retinal ganglion cells (RGCs) have a well-established PCD (P0-P10). In retinal cell cultures from P2 rats 50% of RGCs die after 48 hours. Microglial cells enter in the retina during early development period and are naturally activated by PCD. Microglia polarization is classified in M1 (proinflammatory and neurotoxic) and M2 (anti-inflammatory and neuroprotective) that expresses high levels of Arginase-1, IL-1Ra and BDNF. Arginase-1 hydrolyses arginine to ornithine and urea, limiting arginine for nitric oxide (NO) synthesis characteristic of M1-microglia. IL-4 is known to switch M1 to M2 microglia. Ouabain (OUA) 3nM is a steroid glycoside with well-known immunomodulatory action. OUA increases RGC survival after 48h in culture; an effect mediated by cytokine production.