Interleukin-1β induces pericyte apoptosis via the NF-κB pathway in diabetic retinopathy

초록

Pericytes play a crucial role in preventing endothelial permeability by maintaining the integrity of tight junctions in endothelial cells; however, early pathological change in diabetic retinopathyis pericyte loss, which can lead to visual impairment by increasing endothelial permeability. Therefore, finding proteins and mechanisms that cause pericyte loss in diabetic retinopathy is beneficial for attenuating vision impairment. The present study focused on the effect of IL-1 beta on pericyte loss and endothelial permeability in diabetic retinopathy. It was demonstrated that IL-1 beta increased in the diabetic mouse retina and that the source of IL-1 beta could be endothelial cells and microglia. IL-1 beta induced pericyte apoptosis via NFkB activation under high glucose conditions, but did not induce endothelial cell apoptosis. Moreover, IL-1 beta did not affect permeability in the endothelial cell monolayer; however, when cocultured with pericytes and endothelial cells, it increased endothelial cell permeability by reducing the amount of tight junction protein in endothelial cells. Furthermore, NF-kappa B inhibitor restored the altered permeability and tight junction protein expression in endothelial cells induced by IL-1 beta in cocultures of pericytes and endothelial cells. Collectively, IL-1 beta induced pericyte apoptosis via NF-kappa B activation under high glucose conditions, thereby increasing endothelial permeability in diabetic retinopathy. Blocking IL-1 beta/NF-kappa B signaling could be a promising therapeutic target to prevent pericyte loss in diabetic retinopathy. (c) 2021 Elsevier Inc. All rights reserved.

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