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Effects of a Rho kinase inhibitor on the sequential expression of ICAM-1, HIF-1α, Bcl-2 and caspase-3 in the retina of rats with oxygen-induced retinopathy.

Abstract：

:The aim of the present study was to evaluate the effects of blocking the Rho kinase pathway on non-perfused regions and angiogenesis in the retina of rats using a rat model of oxygen-induced retinopathy (OIR) by observing the sequential expression of intercellular adhesion molecule-1 (ICAM-1), hypoxia-inducible factor-1 (HIF-1), B-cell lymphoma/leukemia-2 gene (Bcl-2) and caspase-3 mRNA following the administration of the Rho kinase inhibitor, fasudil (FSD). A total of 240 newborn rats were randomly divided into a normoxia control (N) group, a hyperoxia (H) group and a H + FSD (HF) group. The rats were sacrificed, and the eyes were enucleated from postnatal day (P)12 to P21. Samples were prepared for retinal flat mounts, mRNA and protein quantification. On P14, a higher number of circuitous retinal veins was observed in the H group compared with the HF group. In the HF group, the avascular area was significantly reduced compared with the H group on P18 (P<0.01). In the HF group, the mRNA expression of Bcl-2 was significantly increased on P15 compared with the N and H group (P<0.01). On P15 and P17 in the H group and on P13 in the HF group, the mRNA expression of ICAM‑1 was significantly increased compared with the other groups (P<0.05). In the H and HF group, the expression of HIF-1α was significantly increased on P12 compared with the N group (P<0.05). On P19 and P21, HIF-1α expression was significantly increased to a maximum level in the HF group compared with the H and N group (P<0.01). In conclusion, these results suggest that FSD inhibits the expression of ICAM-1, assisting in the release of Bcl-2, suppressing caspase-3. In the HF group, the retinal flat mounts revealed that FSD had a vasorelaxant effect. On P18, a double-layered retinal vascular network was formed, and the number of non-perfused regions was significantly reduced. However, the late-phase peak expression of HIF-1α resulted in an inevitable increase in vascular endothelial growth factor expression and further accelerated neovascularization and vascular reconstruction in the immature retinal model.

journal_name

Int J Mol Med

journal_title

International journal of molecular medicine

authors

Wang H,Chen X

doi

10.3892/ijmm.2013.1410

subject

Has Abstract

pub_date

2013-08-01 00:00:00

pages

457-63

issue

eissn

1107-3756

issn

1791-244X

journal_volume

pub_type

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Effects of a Rho kinase inhibitor on the sequential expression of ICAM-1, HIF-1α, Bcl-2 and caspase-3 in the retina of rats with oxygen-induced retinopathy.