Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41598-018-21198-z
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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