Interleukin–1 beta and retinal microvascular cell death in diabetes

Abstract

Abstract: : Aim: Recent studies have shown that the cellular and clinical elements of diabetic retinopathy share many features with chronic inflammation. In the pathogenesis of diabetic retinopathy retinal capillary cells undergo accelerated apoptosis. The aim of our study is to examine the role of cytokine interleukin–1ß (IL–1ß) in retinal capillary cell death in diabetes, and to elucidate the possible mechanism involved. Methods: The effect of addition of IL–1ß on nitric oxide (NO), NF–kB activation and apoptosis was determined in bovine retinal endothelial cells incubated in normal and high glucose conditions, and was confirmed using interleukin–1 receptor antagonist (IL–1ra). The effect of glucose on the expression of IL–1ß in the endothelial cells was also investigated by western blot technique. Results: Incubation of retinal endothelial cells with human recombinant IL–1ß for 3–5 days elevated NO levels by about 80% and activated NF–kB by 40% as compared to that obtained from the cells incubated without IL–1ß. In the same cells apoptosis was increased by 70% and caspase–3 activity by 40%. Addition of IL–1ß in 20mM glucose medium further increased NO and NF–kB, and accelerated apoptosis. IL–1ra significantly decreased glucose–induced abnormalities and apoptosis of the endothelial cells. Incubation of endothelial cells in high glucose increased IL–1ß expression by 60% as compared to the cells incubated in 5mM glucose (P<0.05). Conclusions: IL–1ß accelerates apoptosis of retinal capillary cells via activation of NF–kB, and the process is exacerbated in high glucose conditions. These results offer a possible rationale to test whether IL–1ß receptor antagonists could inhibit the development of diabetic retinopathy.

Keywords: diabetic retinopathy • cytokines/chemokines • apoptosis/cell death