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EBioMedicine. 2016 May;7:35-49. doi: 10.1016/j.ebiom.2016.03.048. Epub 2016 Apr 20.

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

Author information

1
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, Mexico.
2
Institut National de la Santé et de la Recherche Médicale, U1185, Université Paris-Sud, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre 94270, France.
3
Institut National de la Santé et de la Recherche Médicale, U1151, Institut Necker Enfants Malades, Université Paris-Descartes, Faculté de Médecine, Sorbonne Paris Cité, 75014, France.
4
Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, 76230 Querétaro, Mexico. Electronic address: stephaniethebault@gmail.com.

Abstract

The 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 Ca(2+) 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.

KEYWORDS:

Age-related retinal degeneration; Antioxidant; Prolactin; Retinal pigment epithelium; SIRT2; TRPM2 channels

PMID:
27322457
PMCID:
PMC4909382
DOI:
10.1016/j.ebiom.2016.03.048
[Indexed for MEDLINE]
Free PMC Article

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