The NLRP3 Inflammasome May Contribute to Pathologic Neovascularization in the Advanced Stages of Diabetic Retinopathy
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...
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Nature Portfolio
2018
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oai:doaj.org-article:f5819ad73a044bfe965b05e365cb38eb2021-12-02T15:08:05ZThe NLRP3 Inflammasome May Contribute to Pathologic Neovascularization in the Advanced Stages of Diabetic Retinopathy10.1038/s41598-018-21198-z2045-2322https://doaj.org/article/f5819ad73a044bfe965b05e365cb38eb2018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-21198-zhttps://doaj.org/toc/2045-2322Abstract 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-1β 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-1β 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.Shyam S. ChaurasiaRayne R. LimBhav H. ParikhYeo Sia WeyBo Bo TunTien Yin WongChi D. LuuRupesh AgrawalArkasubhra GhoshAlessandra MortellaroElizabeth RackoczyRajiv R. MohanVeluchamy A. BarathiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-15 (2018) |
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DOAJ |
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EN |
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Medicine R Science Q |
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Medicine R Science Q Shyam S. Chaurasia Rayne R. Lim Bhav H. Parikh Yeo Sia Wey Bo Bo Tun Tien Yin Wong Chi D. Luu Rupesh Agrawal Arkasubhra Ghosh Alessandra Mortellaro Elizabeth Rackoczy Rajiv R. Mohan Veluchamy A. Barathi The NLRP3 Inflammasome May Contribute to Pathologic Neovascularization in the Advanced Stages of Diabetic Retinopathy |
| description |
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-1β 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-1β 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. |
| format |
article |
| author |
Shyam S. Chaurasia Rayne R. Lim Bhav H. Parikh Yeo Sia Wey Bo Bo Tun Tien Yin Wong Chi D. Luu Rupesh Agrawal Arkasubhra Ghosh Alessandra Mortellaro Elizabeth Rackoczy Rajiv R. Mohan Veluchamy A. Barathi |
| author_facet |
Shyam S. Chaurasia Rayne R. Lim Bhav H. Parikh Yeo Sia Wey Bo Bo Tun Tien Yin Wong Chi D. Luu Rupesh Agrawal Arkasubhra Ghosh Alessandra Mortellaro Elizabeth Rackoczy Rajiv R. Mohan Veluchamy A. Barathi |
| author_sort |
Shyam S. Chaurasia |
| title |
The NLRP3 Inflammasome May Contribute to Pathologic Neovascularization in the Advanced Stages of Diabetic Retinopathy |
| title_short |
The NLRP3 Inflammasome May Contribute to Pathologic Neovascularization in the Advanced Stages of Diabetic Retinopathy |
| title_full |
The NLRP3 Inflammasome May Contribute to Pathologic Neovascularization in the Advanced Stages of Diabetic Retinopathy |
| title_fullStr |
The NLRP3 Inflammasome May Contribute to Pathologic Neovascularization in the Advanced Stages of Diabetic Retinopathy |
| title_full_unstemmed |
The NLRP3 Inflammasome May Contribute to Pathologic Neovascularization in the Advanced Stages of Diabetic Retinopathy |
| title_sort |
nlrp3 inflammasome may contribute to pathologic neovascularization in the advanced stages of diabetic retinopathy |
| publisher |
Nature Portfolio |
| publishDate |
2018 |
| url |
https://doaj.org/article/f5819ad73a044bfe965b05e365cb38eb |
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