June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Activation of NLRP3 Inflammasome in Proliferative Diabetic Retinopathy
Author Affiliations & Notes
  • Veluchamy A Barathi
    Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
    Translational Pre-Clinical Model Platform, Singapore Eye Research Institute, Singapore, Singapore
  • Rayne R. Lim
    Retina Research Group, Singapore Eye Research Institute, Singapore, Singapore
  • Bhav H. Parikh
    Retina Research Group, Singapore Eye Research Institute, Singapore, Singapore
  • Yeo S. Wey
    Translational Pre-Clinical Model Platform, Singapore Eye Research Institute, Singapore, Singapore
  • Tien Yin Wong
    Retina Research Group, Singapore Eye Research Institute, Singapore, Singapore
    Vitreo-Retina, Singapore National Eye Centre, Singpaore, Singapore
  • Alessandra Mortellaro
    Singapore Immunology Network (SIgN), Agency of Science, Technology and Research (A*STAR), Singapore, Singapore
  • Shyam S Chaurasia
    Retina Research Group, Singapore Eye Research Institute, Singapore, Singapore
    Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
  • Footnotes
    Commercial Relationships Veluchamy Barathi, None; Rayne R. Lim, None; Bhav H. Parikh, None; Yeo S. Wey, None; Tien Yin Wong, None; Alessandra Mortellaro, None; Shyam Chaurasia, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 3487. doi:
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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)

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Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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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