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Nathaniel Walter York, Hannah Labarge, Allison Lutz, De-Ann M Pillers, Nader Sheibani, Bikash R Pattnaik; Oxytocin Receptor Expression in the Retinal Pigment Epithelium Increases with Retinal Maturation. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3117. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
We have demonstrated the expression of oxytocin receptor (OXTR) in the retinal pigment epithelium, shown that oxytocin (OXT) is present in the extracellular matrix around the cone photoreceptors and that OXT activates RPE-OXTR signaling. However, a precise role for oxytocin in retinal function has not been defined. In this study, we use a mouse model to delineate the ontogeny of OXTR. We further explore the possibility that OXT may contribute to vascular development or maintenance.
We determine the fold-change in RPE OXTR expression in RPE isolated from mice aged p5, p10, p15 and p20, relative to an adult mouse by qPCR. 18S RNA served as an internal mRNA control. hRPE cells and primary mouse RPE were used for angiogenesis assays. Human angiogenesis PCR array was used to quantify gene expression changes in response to OXT treatment of hRPE. Mouse VEGF, IGF-1 and β-Actin primers were used to isolate mouse RPE mRNA. ELISA was performed following OXT treatment of hRPE cells. We also assessed the migration and capillary morphogenesis of retinal endothelial cells incubated with conditioned medium collected from RPE cells incubated with OXT.
The mRNA isolated from RPE showed reduced OXTR expression by 0.046 (+.089/-0.024) fold in P5, 0.24 (+2.52/-0.023)-fold in P10 and 0.04 (+.42/-0.01)-fold in P15 as compared to adult, which was significant (p<0.05) for all timepoints except P10. We observed a large variation in OXTR expression within each time point. The angiogenesis PCR array demonstrated altered expression in a small number of genes in hRPE cells while our mouse RPE did not show any change in the genes assayed. ELISA data were consistent with the gene expression studies, demonstrating no alteration in VEGF level with 0.1 or 10 μM OXT (p>0.05). OXT-treated RPE had no impact on retinal vascular endothelial cell tube formation or migration relative to conditioned media without OXT (p>0.05).
There is an increase in OXTR expression in the RPE as the retina matures. Our findings don’t account for a possible differential expression of OXTR in RPE cells based on cell type or cell location within the retina. We were also able to demonstrate that OXTR signaling does not influence the expression or secretion of major angiogenic factors in the RPE under baseline conditions. Further study is needed to determine if there is any response in pathologic conditions.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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