Inhibition of LY294002 in retinal neovascularization via down-regulation the PI3K/AKT-VEGF pathway in vivo and in vitro
AIM: To investigate the effects of the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 on retinal neovascularization (RNV) in the oxygen-induced retinopathy (OIR) mouse model and human umbilical vein endothelial cells (HUVECs). METHODS: C57BL/6J mice were randomly divided into normoxia-cont...
Main Authors: | , |
---|---|
Format: | Article |
Language: | English |
Published: |
Press of International Journal of Ophthalmology (IJO PRESS)
2018-08-01
|
Series: | International Journal of Ophthalmology |
Subjects: | |
Online Access: | http://www.ijo.cn/en_publish/2018/8/20180806.pdf |
id |
doaj-feda0322943d4cb5943e4b96dbf47645 |
---|---|
record_format |
Article |
spelling |
doaj-feda0322943d4cb5943e4b96dbf476452020-11-25T02:45:33ZengPress of International Journal of Ophthalmology (IJO PRESS)International Journal of Ophthalmology2222-39592227-48982018-08-011181284128910.18240/ijo.2018.08.06Inhibition of LY294002 in retinal neovascularization via down-regulation the PI3K/AKT-VEGF pathway in vivo and in vitroYu Di0Xiao-Long Chen1Department of Ophthalmology, Shengjing Affiliated Hospital, China Medical University, Shenyang 110004, Liaoning Province, ChinaDepartment of Ophthalmology, Shengjing Affiliated Hospital, China Medical University, Shenyang 110004, Liaoning Province, ChinaAIM: To investigate the effects of the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 on retinal neovascularization (RNV) in the oxygen-induced retinopathy (OIR) mouse model and human umbilical vein endothelial cells (HUVECs). METHODS: C57BL/6J mice were randomly divided into normoxia-control, OIR-control and LY294002 treatment groups. LY294002 or phosphate-buffered solution was intraperitoneally injected daily into mouse pups from P6 to P9 in LY294002 treatment group or OIR-control group. Morphological and pathological changes in RNV, as well as expression levels of PI3K, serine-threonine kinase (AKT) and vascular endothelial growth factor (VEGF) were observed. HUVECs treating with LY294002 were exposed to hypoxia; the expression of PI3K, AKT and VEGF were examined by Western blot and RT-PCR analyses. RESULTS: Compared with the OIR-control group, LY294002 significantly inhibit RNV. Adenosine diphosphatase (ADPase) staining and hematoxylin and eosin staining indicated that the clock hour scores of neovascularization and the nuclei of pre-retinal neovascular cells in the LY294002 treatment group were clearly less than those in the OIR-control group (1.41±0.52 vs 6.20±1.21; 10.50±1.58 vs 22.25±1.82, both P<0.05). Intravitreal injection of LY294002 (in the LY294002 treatment group) markedly decreased PI3K/AKT-VEGF expression compared with the OIR-control group by immunohistochemistry, Western blotting and RT-PCR (all P<0.05). In HUVECs treated with hypoxia, expression of PI3K, AKT and VEGF were downregulated in the hypoxia-LY294002 group (all P<0.05). CONCLUSION: The PI3K inhibitor LY294002 can inhibit RNV by downregulating PI3K, AKT, and VEGF expression in vivo and in vitro. LY294002 may provide an effective method for preventing retinopathy of prematurity (ROP).http://www.ijo.cn/en_publish/2018/8/20180806.pdf1289vascular endothelial growth factorphosphatidylinositol 3-kinaseLY294002retinopathy of prematurityretinal neovascularization |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yu Di Xiao-Long Chen |
spellingShingle |
Yu Di Xiao-Long Chen Inhibition of LY294002 in retinal neovascularization via down-regulation the PI3K/AKT-VEGF pathway in vivo and in vitro International Journal of Ophthalmology 1289 vascular endothelial growth factor phosphatidylinositol 3-kinase LY294002 retinopathy of prematurity retinal neovascularization |
author_facet |
Yu Di Xiao-Long Chen |
author_sort |
Yu Di |
title |
Inhibition of LY294002 in retinal neovascularization via down-regulation the PI3K/AKT-VEGF pathway in vivo and in vitro |
title_short |
Inhibition of LY294002 in retinal neovascularization via down-regulation the PI3K/AKT-VEGF pathway in vivo and in vitro |
title_full |
Inhibition of LY294002 in retinal neovascularization via down-regulation the PI3K/AKT-VEGF pathway in vivo and in vitro |
title_fullStr |
Inhibition of LY294002 in retinal neovascularization via down-regulation the PI3K/AKT-VEGF pathway in vivo and in vitro |
title_full_unstemmed |
Inhibition of LY294002 in retinal neovascularization via down-regulation the PI3K/AKT-VEGF pathway in vivo and in vitro |
title_sort |
inhibition of ly294002 in retinal neovascularization via down-regulation the pi3k/akt-vegf pathway in vivo and in vitro |
publisher |
Press of International Journal of Ophthalmology (IJO PRESS) |
series |
International Journal of Ophthalmology |
issn |
2222-3959 2227-4898 |
publishDate |
2018-08-01 |
description |
AIM: To investigate the effects of the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 on retinal neovascularization (RNV) in the oxygen-induced retinopathy (OIR) mouse model and human umbilical vein endothelial cells (HUVECs).
METHODS: C57BL/6J mice were randomly divided into normoxia-control, OIR-control and LY294002 treatment groups. LY294002 or phosphate-buffered solution was intraperitoneally injected daily into mouse pups from P6 to P9 in LY294002 treatment group or OIR-control group. Morphological and pathological changes in RNV, as well as expression levels of PI3K, serine-threonine kinase (AKT) and vascular endothelial growth factor (VEGF) were observed. HUVECs treating with LY294002 were exposed to hypoxia; the expression of PI3K, AKT and VEGF were examined by Western blot and RT-PCR analyses.
RESULTS: Compared with the OIR-control group, LY294002 significantly inhibit RNV. Adenosine diphosphatase (ADPase) staining and hematoxylin and eosin staining indicated that the clock hour scores of neovascularization and the nuclei of pre-retinal neovascular cells in the LY294002 treatment group were clearly less than those in the OIR-control group (1.41±0.52 vs 6.20±1.21; 10.50±1.58 vs 22.25±1.82, both P<0.05). Intravitreal injection of LY294002 (in the LY294002 treatment group) markedly decreased PI3K/AKT-VEGF expression compared with the OIR-control group by immunohistochemistry, Western blotting and RT-PCR (all P<0.05). In HUVECs treated with hypoxia, expression of PI3K, AKT and VEGF were downregulated in the hypoxia-LY294002 group (all P<0.05).
CONCLUSION: The PI3K inhibitor LY294002 can inhibit RNV by downregulating PI3K, AKT, and VEGF expression in vivo and in vitro. LY294002 may provide an effective method for preventing retinopathy of prematurity (ROP). |
topic |
1289 vascular endothelial growth factor phosphatidylinositol 3-kinase LY294002 retinopathy of prematurity retinal neovascularization |
url |
http://www.ijo.cn/en_publish/2018/8/20180806.pdf |
work_keys_str_mv |
AT yudi inhibitionofly294002inretinalneovascularizationviadownregulationthepi3kaktvegfpathwayinvivoandinvitro AT xiaolongchen inhibitionofly294002inretinalneovascularizationviadownregulationthepi3kaktvegfpathwayinvivoandinvitro |
_version_ |
1724761978305511424 |