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Title: | The NLRP3 Inflammasome May Contribute to Pathologic Neovascularization in the Advanced Stages of Diabetic Retinopathy | Authors: | Chaurasia, S.S Lim, R.R Parikh, B.H Wey, Y.S Tun, B.B Wong, T.Y Luu, C.D Agrawal, R Ghosh, A Mortellaro, A Rackoczy, E Mohan, R.R Barathi, V.A |
Keywords: | cryopyrin cytokine glial fibrillary acidic protein glial fibrillary astrocytic protein, mouse Ins2 protein, mouse insulin Nlrp3 protein, mouse vascular endothelial growth factor A, mouse vasculotropin A animal diabetic retinopathy diagnostic imaging disease model electroretinography fluorescence angiography genetics human metabolism mouse neovascularization (pathology) optical coherence tomography pathology retina transgenic mouse Animals Cytokines Diabetic Retinopathy Disease Models, Animal Electroretinography Fluorescein Angiography Glial Fibrillary Acidic Protein Humans Insulin Mice Mice, Transgenic Neovascularization, Pathologic NLR Family, Pyrin Domain-Containing 3 Protein Retina Tomography, Optical Coherence Vascular Endothelial Growth Factor A |
Issue Date: | 2018 | Citation: | Chaurasia, S.S, Lim, R.R, Parikh, B.H, Wey, Y.S, Tun, B.B, Wong, T.Y, Luu, C.D, Agrawal, R, Ghosh, A, Mortellaro, A, Rackoczy, E, Mohan, R.R, Barathi, V.A (2018). The NLRP3 Inflammasome May Contribute to Pathologic Neovascularization in the Advanced Stages of Diabetic Retinopathy. Scientific Reports 8 (1) : 2847. ScholarBank@NUS Repository. https://doi.org/10.1038/s41598-018-21198-z | Rights: | Attribution 4.0 International | Abstract: | Diabetic retinopathy (DR) is a retinal microvascular disease characterized by inflammatory and angiogenic pathways. In this study, we evaluated NLRP3 inflammasome in a double transgenic mouse model, Akimba (Ins2 Akita xVEGF +/-), which demonstrates hyperglycemia, vascular hyperpermeability and neovascularization seen in the proliferative DR. Retinal structural integrity, vascular leakage and function were examined by fundus photography, fluorescein angiography, optical coherence tomography, retinal flat mounts, laser speckle flowgraphy (LSFG), and electroretinography in Akimba and its parental strains, Akita (Ins2 Akita ) and Kimba (trVEGF029) mice. Inflammatory mechanisms involving NLRP3 inflammasome were investigated using real time-PCR, immunohistochemistry, ELISA and western blots. We observed an increased vascular leakage, reduced retinal thickness, and function in Akimba retina. Also, Akimba retina depicts decreased relative flow volume measured by LSFG. Most importantly, high levels of IL-1? along with increased NLRP3, ASC, and Caspase-1 at mRNA and protein levels were observed in Akimba retina. However, the in vivo functional role remains undefined. In conclusion, increased activation of macroglia (GFAP), microglia (Iba-1 and OX-42) and perivascular macrophages (F4/80 and CD14) together with pro-inflammatory (IL-1? and IL-6) and pro-angiogenic markers (PECAM-1, ICAM-1, VEGF, Flt-1, and Flk-1), suggested a critical role for NLRP3 inflammasome in the Akimba mouse model depicting advanced stages of DR pathogenesis. © 2018 The Author(s). | Source Title: | Scientific Reports | URI: | https://scholarbank.nus.edu.sg/handle/10635/177828 | ISSN: | 20452322 | DOI: | 10.1038/s41598-018-21198-z | Rights: | Attribution 4.0 International |
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