Abstract
Diabetic retinopathy is a leading complication of diabetes. Death of capillary cells with resulting capillary degeneration is a central feature of this disease. Chronic low-grade inflammation has been linked to the development of retinal capillary degeneration in diabetes. CD40 is an upstream inducer of a broad range of inflammatory responses in the diabetic retina and is required for death of retinal capillary cells. Recent studies uncovered CD40 as a novel inducer of purinergic signaling and identified the CD40-ATP-P2X7 pathway as having a key role in the induction of inflammation in the diabetic retina and programmed cell death of retinal endothelial cells.
Highlights
Diabetes is one of the most common chronic diseases in the world
Microangiopathy is a major cause of morbidity and mortality in diabetics and the retina is one of the main tissues affected by diabetic microvascular disease
The CD40–CD154 pathway is activated in diabetes: CD40 expression is increased in Müller cells, retinal endothelial cells (REC) and microglia/macrophages in diabetic mice [20], and blood levels of CD154 are increased in diabetic mice and patients with microangiopathy [21,26,27,28]
Summary
Diabetes is one of the most common chronic diseases in the world. The prevalence of diabetes worldwide in 2014 increased to 8.5% in adults over 18 years of age leading to the estimation that there are 422 million patients with diabetes in the world [1]. Vascular lesions of DR include the death of retinal endothelial cells and pericytes [4]. This leads to the transformation of capillaries into tubes of basement membrane devoid of cells (capillary degeneration). Various mechanisms appear to link chronic hyperglycemia to the development of microangiopathy These include oxidative stress, increased polyol pathway flux, increased hexosamine pathway flux, activation of protein kinase C and increased formation of advanced glycation-end products [6]. The correlation between CCL2 protein levels in the vitreous with the clinical stage of diabetic proliferative retinopathy [17] suggests a pathogenic role for this chemokine
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