Abstract
As a clinical manifestations of diabetic retinopathy (DR), pericytes (PCs) loss from the capillary walls is thought to be an initial pathological change responsible for the breakdown of the blood-retinal barrier (BRB). This study was performed to investigate the effects of ursodeoxycholic acid (UDCA) in PC depletion mice by injection of an antibody against platelet-derived growth factor reception-β (PDGFR-β clone APB5). To assess the integrity of the retinal vessels, their density, diameters, vessel branching points, and number of acellular capillaries were evaluated. While all types of retinal vessels became enlarged in APB5-induced mice, treatment with UDCA rescued the vasculature; the vessel density, diameter of the veins and capillaries, and vessel branching points were significantly lower in mice treated with UDCA. Although APB5-induced mice displayed progressive exacerbation of retinal edema, whole retinal thickness upon treatment with UDCA was significantly decreased. Additionally, UDCA reduced the expression of F4/80+ macrophages in the APB5-induced retina according to immunofluorescent labeling. UDCA also reduced the increased expression of angiogenic factors and inflammatory mediators (vascular endothelial growth factor, intercellular adhesion molecule-1, and monocyte chemotactic protein-1). These findings suggest that UDCA can be used to prevent the progression of and treat DR.
Highlights
Diabetes and its related complications, including retinopathy, have a great social and economic burden worldwide[1,2]
PC recruitment was completely inhibited by administration of anti-platelet derived growth factor receptor (PDGFR)-β mAb to neonatal mice[22,23], in which the disease severity corresponded to the extent of PC depletion from developing retinal vessels, resulting in retinal collapse and blood-retinal barrier (BRB) breakdown[22]
Our model improves on previous attempts, as hyperglycemic animal models such as STZ-induced mice model fail to fully mimic the pathophysiology of human diabetic retinopathy (DR), in terms of retinal vascular changes
Summary
Diabetes and its related complications, including retinopathy, have a great social and economic burden worldwide[1,2]. The molecular and cellular mechanisms underlying barrier dysfunction of PC-free retinal vessels remain unknown[22] This has made it difficult to determine whether the effect of UDCA listed above contributes to the development of late vascular changes observed in human diabetic retinas. PC recruitment was completely inhibited by administration of anti-platelet derived growth factor receptor (PDGFR)-β mAb (clone APB5) to neonatal mice[22,23], in which the disease severity corresponded to the extent of PC depletion from developing retinal vessels, resulting in retinal collapse and BRB breakdown[22]. We used an APB5-induced PC depletion model to investigate whether UDCA results in retinal vessel maintenance and inhibits inflammatory responses, thereby contributing to the attenuation of DR
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