Oxytocin expression and function in the posterior retina: a novel signaling pathway

Invest Ophthalmol Vis Sci. 2015 Jan 15;56(2):751-60. doi: 10.1167/iovs.14-15646.

Abstract

Purpose: Oxytocin (OXT) is recognized as an ubiquitously acting nonapeptide hormone that is involved in processes ranging from parturition to neural development. Its effects are mediated by cell signaling that occurs as a result of oxytocin receptor (OXTR) activation. We sought to determine whether the OXT-OXTR signaling pathway is also expressed within the retina.

Methods: Immunohistochemistry using cell-specific markers was used to localize OXT within the rhesus retina. Reverse transcriptase PCR and immunohistochemistry were used to assess the expression of OXTR in both human and rhesus retina. Single-cell RT-PCR and Western blot analyses were used to determine the expression of OXTR in cultured human fetal RPE (hfRPE) cells. Human fetal RPE cells loaded with FURA-2 AM were studied by ratiometric Ca(2+) imaging to assess transient mobilization of intracellular Ca(2+) ([Ca(2+)]i).

Results: Oxytocin was expressed in the cone photoreceptor extracellular matrix of the rhesus retina. Oxytocin mRNA and protein were expressed in the human and rhesus RPE. Oxytocin mRNA and protein expression were observed in cultured hfRPE cells, and exposure of these cells to 100 nM OXT induced a transient 79 ± 1.5 nM increase of [Ca(2+)]i.

Conclusions: Oxytocin and OXTR are present in the posterior retina, and OXT induces an increase in hfRPE [Ca(2+)]i. These results suggest that the OXT-OXTR signaling pathway is active in the retina. We propose that OXT activation of the OXTR occurs in the posterior retina and that this may serve as a paracrine signaling pathway that contributes to communication between the cone photoreceptor and the RPE.

Keywords: GPCR; cell-calcium; neuropeptide; oxytocin receptor; retinal pigment epithelium; signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cells, Cultured
  • Gene Expression Regulation, Developmental*
  • Humans
  • Immunohistochemistry
  • Macaca mulatta
  • Oxytocin / biosynthesis
  • Oxytocin / genetics*
  • RNA, Messenger / genetics*
  • Real-Time Polymerase Chain Reaction
  • Retinal Pigment Epithelium / embryology
  • Retinal Pigment Epithelium / metabolism*
  • Signal Transduction

Substances

  • RNA, Messenger
  • Oxytocin