RAPGEF3 and diabetic retinopathy: We focused on Epac1 as a downstream mediator of Compound 49b actions, as both PKA and Epac1 are reported to regulate endothelial cell barrier functions.8 While it is probable that both PKA and Epac1 may function in barrier actions, work in HUVEC cells showed that Epac1 had a regulatory role in cell junctions through VE-cadherin.12 As we have already demonstrated that Compound 49b activates PKA to protect REC from apoptosis,9 we focused on alternative downstream factors that may regulate specific actions common in diabetic retinopathy.