June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
A novel HIF1α inhibitor KC7F2 attenuates oxygen-induced retinal neovascularization
Author Affiliations & Notes
  • Xiaoyu Tang
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
  • Kaixuan Cui
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
  • Peiqi Wu
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
  • Yue Xu
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
  • Xiaoling Liang
    Sun Yat-Sen University Zhongshan Ophthalmic Center State Key Laboratory of Ophthalmology, Guangzhou, Guangdong, China
  • Footnotes
    Commercial Relationships   Xiaoyu Tang None; Kaixuan Cui None; Peiqi Wu None; Yue Xu None; Xiaoling Liang None
  • Footnotes
    Support  the National Natural Science Foundation of China (81870668)
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 2675. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Xiaoyu Tang, Kaixuan Cui, Peiqi Wu, Yue Xu, Xiaoling Liang; A novel HIF1α inhibitor KC7F2 attenuates oxygen-induced retinal neovascularization. Invest. Ophthalmol. Vis. Sci. 2022;63(7):2675.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : KC7F2 is a novel molecule compound that can inhibit the translation of hypoxia-inducible factor 1α (HIF1α). The purpose of the present study was to investigate whether KC7F2 played a role in oxygen-induced retinal neovascularization (RNV).

Methods : Oxygen-induced retinopathy (OIR) models in C57BL/6J mice and Sprague-Dawley rats were used for in vivo study. After intraperitoneal injections of KC7F2, RNV was detected by immunofluorescence and hematoxylin-eosin staining. Retinal inflammation was explored by immunofluorescence. EdU incorporation assay, cell counting kit-8 assay, scratch test, transwell assay and matrigel assay were used to evaluate the effect of KC7F2 on the proliferation, migration and tube formation of human umbilical vein endothelial cell (HUVEC) induced by vascular endothelial growth factor (VEGF) in vitro. Protein expression was examined by Western blot.

Results : KC7F2 treatment (10 mg/kg/d) in OIR mice significantly attenuated pathological neovascularization (p=0.0005), and decreased the number of preretinal neovascular cell nuclei (p=0.0071), without changing avascular area (p=0.3583), which showed the same trends in OIR rats. Consistently, after the KC7F2 intervention (10 μM), cell proliferation was inhibited in VEGF-induced HUVEC (p=0.0172), which was in agreement with the trend observed in retinas of OIR mice (p<0.0001). Meanwhile, KC7F2 suppressed VEGF-induced HUVEC migration (p=0.0003) and tube formation (p=0.0135), and decreased the density of leukocytes (p=0.0027) and microglia (p=0.0001) co-localizing neovascular areas in the retinas. Moreover, HIF1α-VEGF pathway activated in retinas of OIR mice and hypoxia-induced HUVEC, was suppressed by KC7F2 treatment.

Conclusions : The current study showed the anti-angiogenic effect of KC7F2 via HIF1α-VEGF pathway, suggesting that it might be an effective drug for RNV treatment.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×