Abstract
Diabetic retinopathy is considered a neurovascular disorder, hyperglycemia being considered the main risk factor for this pathology. Diabetic retinopathy also presents features of a low-grade chronic inflammatory disease, including increased levels of cytokines in the retina, such as interleukin-1 beta (IL-1β). However, how high glucose and IL-1β affect the different retinal cell types remains to be clarified. In retinal neural cell cultures, we found that IL-1β and IL-1RI are present in microglia, macroglia, and neurons. Exposure of retinal neural cell cultures to high glucose upregulated both mRNA and protein levels of IL-1β. High glucose decreased microglial and macroglial cell proliferation, whereas IL-1β increased their proliferation. Interestingly, under high glucose condition, although the number of microglial cells decreased, they showed a less ramified morphology, suggesting a more activated state, as supported by the upregulation of the levels of ED-1, a marker of microglia activation. In conclusion, IL-1β might play a key role in diabetic retinopathy, affecting microglial and macroglial cells and ultimately contributing to neural changes observed in diabetic patients. Particularly, since IL-1β has an important role in retinal microglia activation and proliferation under diabetes, limiting IL-1β-triggered inflammatory processes may provide a new therapeutic strategy to prevent the progression of diabetic retinopathy.
Highlights
Diabetic retinopathy is a leading cause of vision loss and blindness in the western countries and the most common complication of diabetes
Since the retina is composed by different cell types that potentially may produce IL-1β, we first analyzed whether retinal cells present in culture were able to synthesize IL-1β and identified those that can be directly affected by IL-1β, that is, cells that express IL-RI
Since hyperglycemia is considered the main risk factor for diabetic retinopathy [27, 28] and the levels of IL-1β are increased in the retinas of diabetic rats [14,15,16,17], we evaluated the effect of elevated glucose on IL-1β expression in retinal neural cultures in order to evaluate if high glucose per se is capable of upregulating IL-1β expression
Summary
Diabetic retinopathy is a leading cause of vision loss and blindness in the western countries and the most common complication of diabetes. Hyperglycemia is considered the primary pathogenic factor underlying diabetic retinopathy, being the breakdown of blood-retinal barrier (BRB), one of the first alterations clinically evident, and a hallmark of the disease [1]. Early signs of neural dysfunction in the retina, namely, alterations in electroretinograms and loss of colour and contrast sensitivity, occur before the detection of microvascular changes in diabetic patients and animals [2,3,4,5]. Despite the progress in understanding the pathogenesis of diabetic retinopathy, the mechanisms underlying neural dysfunction are far from being completely understood. Growing evidence indicates that diabetic retinopathy has features of a low-grade chronic inflammatory disease. Several genes involved in inflammatory processes are upregulated early in the diabetic rat retina [6, 7]. In the vitreous fluid of diabetic patients, the levels of interleukin-1 beta (IL-1β), IL-6, and tumor necrosis factor (TNF) are increased [8,9,10]
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