Molecular regulation of ERK5 in development of diabetic retinopathy

Diabetic retinopathy (DR) is a major complication of diabetes, and causes pathological changes in retina blood vessels, as the most common cause of vision loss. Extracellular-signal-regulated kinase 5 (ERK5) is the newest discovered member in the mitogen-activated protein kinases (MAPKs) family, and recent evidence demonstrates an essential role of ERK5 signaling in the angiogenesis. However, whether ERK5 signaling may regulate DR development is unknown. Here, we used a streptozocin (STZ)-induce mouse DR model to investigate this question. We detected significant increases in the phosphorylation of ERK5, a signature of ERK5 activation in the purified retinal endothelial cells in DR mice, compared to control mice. In vivo suppression of ERK5 phosphorylation through administration of a specific inhibitor of ERK5 activation, BIX02189, did not prevent the occurrence of STZ-induced diabetes in mice, but significantly alleviated the severity of DR, seemingly through attenuating the retina neovascularization. Thus, our study suggests a previously unappreciated role of ERK5 signaling in DR development.