A Novel Hypoxia-inducible Factor 1α Inhibitor KC7F2 Attenuates Oxygen-induced Retinal Neovascularization.
Invest Ophthalmol Vis Sci
; 63(6): 13, 2022 06 01.
Article
in En
| MEDLINE
| ID: mdl-35695808
ABSTRACT
Purpose:
KC7F2 is a novel molecule compound that can inhibit the translation of hypoxia-inducible factor 1α (HIF1α). It has been reported to exhibit potential antiangiogenic effect. We hypothesized that KC7F2 could inhibit oxygen-induced retinal neovascularization (RNV). The purpose of this study was to investigate this assumption.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 and 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 cells (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 and decreased the number of preretinal neovascular cell nuclei, without changing the avascular area, which showed the same trends in OIR rats. Consistently, after the KC7F2 intervention (10 µM), cell proliferation was inhibited in VEGF-induced HUVEC, which was in agreement with the trend observed in the retinas of OIR mice. Meanwhile, KC7F2 suppressed VEGF-induced HUVEC migration and tube formation, and decreased the density of leukocytes and microglia colocalizing neovascular areas in the retinas. Moreover, the HIF1α-VEGF pathway activated in retinas of OIR mice and hypoxia-induced HUVEC, was suppressed by KC7F2 treatment.Conclusions:
The current study revealed that KC7F2 was able to inhibit RNV effectively via HIF1α-VEGF pathway, suggesting that it might be an effective drug for RNV treatment.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sulfonamides
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Retinopathy of Prematurity
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Retinal Neovascularization
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Disulfides
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Hypoxia-Inducible Factor 1, alpha Subunit
Type of study:
Prognostic_studies
Limits:
Animals
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Humans
/
Newborn
Language:
En
Journal:
Invest Ophthalmol Vis Sci
Year:
2022
Document type:
Article
Affiliation country:
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA