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Veluchamy A Barathi, Rayne R. Lim, Bhav H. Parikh, Yeo S. Wey, Tien Yin Wong, Alessandra Mortellaro, Shyam S Chaurasia; Activation of NLRP3 Inflammasome in Proliferative Diabetic Retinopathy . Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3487.
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© ARVO (1962-2015); The Authors (2016-present)
Proliferative diabetic retinopathy (PDR) is a blinding vitreoretinal disease involving inflammatory and angiogenic components. In this study, we studied NLRP3 inflammasome in a double transgenic mouse model, Akimba (Ins2Akita x VEGF+/-) that combines hyperglycemia and overexpression of vascular endothelial growth factor (VEGF) and displayed majority of the signs of PDR.
Akimba mice and its parental strains, Akita (Ins2Akita) and Kimba (trVEGF029) mice were used in this study. Blood glucose, fundus photography, FFA and ERG was measured in these mice weekly for 12 weeks. Inflammatory pathway and NLRP3 inflammasome was investigated using real time-PCR, immunohistochemistry and western blots.
We found increased levels of IL-1b in all the mouse models, with maximum levels in Akimba retina. This increase was highly correlated with the expression of NLRP3 inflammasome components-ASC, NLRP3, & Caspase-1 and associated with higher levels of pro-inflammatory mediators detected. Results indicated increase in activated macrophages that upregulated NLRP3 inflammasome, possibly in all the retinal layers, which released active IL-1β in the ganglion cell and nerve fiber layer, initiating the autoinflammatory feedback loop and thereby promoting the inflammatory mediators to elicit a severe inflammatory response in PDR.
This study demonstrated the effects of the interplay between VEGF upregulation and hyperglycemia in the Akimba mice retina. We conclude that the Akimba mouse indicates several features of PDR and suggests an important role for NLRP3 inflammasome in the pathogenesis of PDR.
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