April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Prolactin Prevents The High-glucose-induced Reduction Of Paracellular Permeability In Polarized Arpe-19 Cultures
Author Affiliations & Notes
  • Stephanie Thebault
    Instituto de Neurobiologia, Universidad Nacional Autonoma de Mexico, Queretaro, Mexico
  • Edith Arnold
    Instituto de Neurobiologia, Universidad Nacional Autonoma de Mexico, Queretaro, Mexico
  • German Baeza Cruz
    Instituto de Neurobiologia, Universidad Nacional Autonoma de Mexico, Queretaro, Mexico
  • Gonzalo Martinez de la Escalera
    Instituto de Neurobiologia, Universidad Nacional Autonoma de Mexico, Queretaro, Mexico
  • Carmen Clapp
    Instituto de Neurobiologia, Universidad Nacional Autonoma de Mexico, Queretaro, Mexico
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 881. doi:
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      Stephanie Thebault, Edith Arnold, German Baeza Cruz, Gonzalo Martinez de la Escalera, Carmen Clapp; Prolactin Prevents The High-glucose-induced Reduction Of Paracellular Permeability In Polarized Arpe-19 Cultures. Invest. Ophthalmol. Vis. Sci. 2011;52(14):881.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Prolactin (PRL) promotes paracellular movement of ions and small molecules across several types of epithelium, while vasoinhibins, proteolytically-derived PRL fragments that include 16K PRL, are potent inhibitors of the excessive retinal vasopermeability associated with diabetes. Because these proteins are present in rat retina, we examined whether PRL and vasoinhibins could regulate paracellular permeability of retinal pigment epithelium (RPE) under conditions of oxidative injury and hyperglycemia.

Methods: : Western-blot analysis was used to detect the PRL receptor, PRL, and vasoinhibins in the immortalized human RPE cell line ARPE-19. Polarized ARPE-19 monolayers were cultured on permeable transwell filters, and paracellular permeability was measured by assaying tracer flux. PRL and vasoinhibins were applied on the apical side of the ARPE-19 monolayers, and oxidative injury and hyperglycemia were modeled by H(2)O(2) (10 µM) and high glucose (25 mM) treatments, respectively.

Results: : ARPE-19 monolayers expressed PRL, PRL receptors, and vasoinhibins. PRL stimulated by 2- to 3-fold the paracellular permeability of ARPE-19 monolayers at doses of 1 to 100 nM, but did not further enhance the H(2)O(2)-induced increase in permeability. On the other hand, vasoinhibins did not modify the paracellular permeability of ARPE-19 cells either under control conditions or H(2)O(2) challenge. Notably, ARPE-19 monolayers cultured for 5 days with high glucose showed a reduced paracellular permeability that was fully counteracted by PRL.

Conclusions: : These data demonstrate that PRL promotes ARPE-19 permeability via the paracellular pathway under basal conditions, but also under hyperglycemia, as PRL prevents the high-glucose-induced reduction in ARPE-19 permeability. However, PRL did not further enhance oxidative damage in ARPE-19. These findings suggest that PRL acts as an autocrine regulator of the RPE barrier function.Supported by CONACYT 81150.

Keywords: growth factors/growth factor receptors • diabetes • retinal pigment epithelium 
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