June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Caspase-1 Cleaves LRP6 for Wnt/β-catenin Activation in Diabetic Retinopathy
Author Affiliations & Notes
  • Yazhou Qin
    Department of Ophthalmology, First Affiliated Hospital of Xi'an Jiaotong University, China
  • Jingming Li
    Department of Ophthalmology, First Affiliated Hospital of Xi'an Jiaotong University, China
  • Xian Zhang
    Affiliated Eye Hospital of Nanchang University, China
  • Qiuping Liu
    Affiliated Eye Hospital of Nanchang University, China
  • Footnotes
    Commercial Relationships   Yazhou Qin, None; Jingming Li, None; Xian Zhang, None; Qiuping Liu, None
  • Footnotes
    Support  NSFC grants 81960177 and 81740158; Young Talent Scholar Grant 2016KJXX-12; Grant from Jiangxi Provincial Science and Technology Department 20192BAB205049.
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 281. doi:
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    • Get Citation

      Yazhou Qin, Jingming Li, Xian Zhang, Qiuping Liu; Caspase-1 Cleaves LRP6 for Wnt/β-catenin Activation in Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2020;61(7):281.

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

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Abstract

Purpose : Diabetic retinopathy (DR) is a low-grade inflammatory disease characterized by retinal vascular hyper-permeability and pathological neovascularization. Caspase-1 cleaves multiple substrates to mediate a variety of inflammatory cascades. Meanwhile, LRP6/β-catenin pathway plays a causal role in retinal microvasculopathy during DR. Here we hypothesize that caspase-1 contributes to retinal β-catenin activation and inflammatory response by cleaving LRP6 in DR.

Methods : Animal models of streptozotocin (STZ)-induced diabetes and oxygen-induced retinopathy (OIR) were set up with both wild type mice and Capsase-1 deficient mice. Retinal vascular leakage, leukostasis and neovascularization were measured by Evan’s blue method, ConA-lectin perfusion and isolectin IB4 staining, respectively. Expression of truncated LRP6, β-catenin and inflammatory cytokines were determined by western-blot analysis or quantitative RT-PCR.

Results : Retinal expression of active caspase-1 p20 were significantly increased in wild type STZ mice and OIR mice. Meanwhile, increased vascular leakage, adherent leukocytes and aberrant neovascularization were observed retinas of wild-type STZ and OIR mice. However, retinal vascular hyper-permeability, increased vascular leukostasis and pathological neovascularization were significantly ameliorated in Caspase-1 deficient mice. Moreover, Caspase-1 deficient STZ and OIR mice displayed attenuated LRP6 truncation, reduced β-catenin accumulation and down-regulated inflammatory gene expression.

Conclusions : Taken together, these results provide in vivo evidence that Caspase-1 deficiency protects against DR likely through suppression of LRP6/β-catenin activation.

This is a 2020 ARVO Annual Meeting abstract.

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