July 2018
Volume 59, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2018
Loss of NLRP1 Inflammasome Exacerbated Retinal Photoreceptor Damage and Choroidal Neovascularization in Mouse Models of Age-related Macular Degeneration through Reduction of IL-18
Author Affiliations & Notes
  • Jiawei Ren
    First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
  • Xian Zhang
    Affiliated Eye Hospital of Nanchang University, Nanchang, Jiangxi, China
  • QIUPING LIU
    Affiliated Eye Hospital of Nanchang University, Nanchang, Jiangxi, China
  • Qianyan Kang
    First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
  • Jingming Li
    First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
  • Footnotes
    Commercial Relationships   Jiawei Ren, None; Xian Zhang, None; QIUPING LIU, None; Qianyan Kang, None; Jingming Li, None
  • Footnotes
    Support  NSFC Grants 81460163, 81400427 and 81300786; Young Talent Scholar Grant 2016KJXX-12; FRFCU Grant xjj2015015; RFDP Grant 20133601120012; Research Grant from Shaanxi Science and Technology Department 2016JM8029; Research Grants from Jiangxi Education Department GJJ14094, GJJ13175; Research Grants from Jiangxi Science and Technology Department 20142BDH80005, 20142BAB215029, 20132BAB205024.
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 372. doi:
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      Jiawei Ren, Xian Zhang, QIUPING LIU, Qianyan Kang, Jingming Li; Loss of NLRP1 Inflammasome Exacerbated Retinal Photoreceptor Damage and Choroidal Neovascularization in Mouse Models of Age-related Macular Degeneration through Reduction of IL-18. Invest. Ophthalmol. Vis. Sci. 2018;59(9):372.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Age-related macular degeneration (AMD) is a leading cause of blindness in the eldly. Recent studies have reported that inflammasome forming NLRs were implicated in development of AMD. NLRP1 was the first identified NLRs. The aim of this study is to determined contributions of NLRP1 to retinal photoreceptor injuries and choroidal neovascularzation (CNV) in mouse models of AMD.

Methods : NLRP1 deficient (NLRP1-/-) and wild type control (NLRP1+/+) mice were utilized in the study. A mouse model of geographic atrophy AMD was induced by intravenous injection of sodium iodate (SI) and the laser-induced CNV was setup as the mouse model of neovascular AMD. Expression of inflammasome components including NLRP1, caspase-1, and IL-18 were determined by western-blot analysis. Exogenous IL-18 were delivered to mice by intravitreous injection. Cross-sectional structures of mouse retinas were visualized with non-invasive spectral domain optical coherence tomography (OCT). CNV was imaged in vivo with fluorescein angiography and indocyanine green angiography. Photoreceptor apoptosis and CNV formation were further evaluated by TUNEL assay on retinal cryosections and choroidal flatmount staining with GS-IB4.

Results : Expression of NLRP1, caspase-1 p20 and IL-18 were markedly increased in eyecups of both SI- and laser-treated NLRP1+/+ mice, which was significantly inhibited by NLRP1 deficiency. OCT imaging showed disorganized photoreceptor IS/OS structures and reduced ONL thickness in SI-treated NLRP1+/+ mice. These degenerative changes are more severe in NLRP1-/- mouse retinas with irregular folds and rosettes in ONL. TUNEL staining further verified that NLRP1-/- mice were more vulnerable to SI-induced apoptosis of RPE and photoreceptor cells compared with NLRP1+/+ mice. Moreover, lasered NLRP1-/- demonstrated larger CNV volume than NLRP1+/+ mice with both in vivo angiography and in vitro flatmount IB4 staining. Intravitreous administration of IL-18 significantly reversed retinal photoreceptor apoptosis and CNV formation in NLRP1-/- mice.

Conclusions : Collectively, these findings provided strong evidence that NLRP1 may exert its protective effect on retinal photoreceptor degeneration and CNV formation, partially through induction of IL-18. Modulation of NLRP1 inflammasome was highlighted as a promising target for the treatment of AMD.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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