To address the disappointing results of the DIRECT trial, our recent study [64] shows that Ang II increases retinal sEH expression, which is blunted by an AT1 blocker; 11,12-EET exacerbates Ang II-retinal vascular leakage; diabetes (STZ model) induces retinal angiotensinogen and AT1 expression (RAS activation), which is associated with increased retinal sEH expression; and sEH KO (increasing EETs) exacerbates diabetes-induced retinal vascular leakage. Here, EPHX2 is linked to diabetes mellitus.