| First Author | Liu L | Year | 2017 |
| Journal | Mol Vis | Volume | 23 |
| Pages | 1-7 | PubMed ID | 28210097 |
| Mgi Jnum | J:311944 | Mgi Id | MGI:6781573 |
| Citation | Liu L, et al. (2017) Epac1 agonist decreased inflammatory proteins in retinal endothelial cells, and loss of Epac1 increased inflammatory proteins in the retinal vasculature of mice. Mol Vis 23:1-7 |
| abstractText | PURPOSE: Increased inflammatory mediator levels are reported in diabetic retinopathy. We previously reported that beta-adrenergic receptor agonists reduced inflammatory mediators in the diabetic retina; however, these agents cannot be given systemically. Here, we investigated whether Epac1 is key to the protective effects of beta-adrenergic receptor agonists. METHODS: We cultured primary human retinal endothelial cells (RECs) in normal (5 mM) or high (25 mM) glucose and treated them with an Epac1-specific agonist. Additionally, we generated Epac1 conditional vascular endothelial cell knockout mice by breeding Epac1 floxed mice with Cdh5 Cre mice to investigate the role of Epac1 in the retinal levels of tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), nuclear factor kappa beta (NFkappaB), and inhibitor of kappa beta (IkappaB). Confocal microscopy was performed to localize Epac1 in the mouse retina. RESULTS: Data showed that high glucose increased the TNF-alpha and IL-1beta levels in the RECs, which were reduced cells treated with the Epac1 agonist. The loss of Epac1 in the retinas of the conditional knockout mice resulted in statistically significantly increased levels of TNF-alpha and IL-1beta, as well as NFkappaB. CONCLUSIONS: These data indicate that Epac1 may be protective to the retina through inhibition of key inflammatory mediators. |
