Prolactin protects retinal pigment epithelium by inhibiting sirtuin 2-dependent cell death

• Endogenous prolactin is necessary for the viability of retinal pigment epithelium.
• Exogenous prolactin protects retinal pigment epithelium from death upon oxidant insult and advancing age.
• Prolactin exerts its protective actions by inhibiting the oxidant-induced sirtuin 2-dependent activation of TRPM2 channels.As we age, vision declines. This process can be fastened in certain diseases of the retina. The retina is composed of ten layers, among which, one named the retinal pigment epithelium (RPE) is known to become dysfunctional. In particular, RPE cells can die. Here, we demonstrated that the hormone of lactation, prolactin, helps the RPE to survive under conditions that are threatening for the eye and happen during natural aging.

SummaryThe identification of pathways necessary for retinal pigment epithelium (RPE) function is fundamental to uncover therapies for blindness. Prolactin (PRL) receptors are expressed in the retina, but nothing is known about the role of PRL in RPE. Using the adult RPE 19 (ARPE-19) human cell line and mouse RPE, we identified the presence of PRL receptors and demonstrated that PRL is necessary for RPE cell survival via anti-apoptotic and antioxidant actions. PRL promotes the antioxidant capacity of ARPE-19 cells by reducing glutathione. It also blocks the hydrogen peroxide-induced increase in deacetylase sirtuin 2 (SIRT2) expression, which inhibits the TRPM2-mediated intracellular Ca2+ rise associated with reduced survival under oxidant conditions. RPE from PRL receptor-null (prlr−/−) mice showed increased levels of oxidative stress, Sirt2 expression and apoptosis, effects that were exacerbated in animals with advancing age. These observations identify PRL as a regulator of RPE homeostasis.