RGD Reference Report - Baicalein protects against retinal ischemia by antioxidation, antiapoptosis, downregulation of HIF-1alpha, VEGF, and MMP-9 and upregulation of HO-1. - Rat Genome Database

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Baicalein protects against retinal ischemia by antioxidation, antiapoptosis, downregulation of HIF-1alpha, VEGF, and MMP-9 and upregulation of HO-1.

Authors: Chao, HM  Chuang, MJ  Liu, JH  Liu, XQ  Ho, LK  Pan, WH  Zhang, XM  Liu, CM  Tsai, SK  Kong, CW  Lee, SD  Chen, MM  Chao, FP 
Citation: Chao HM, etal., J Ocul Pharmacol Ther. 2013 Jul-Aug;29(6):539-49. doi: 10.1089/jop.2012.0179. Epub 2013 Mar 28.
RGD ID: 10755711
Pubmed: PMID:23537149   (View Abstract at PubMed)
PMCID: PMC3708628   (View Article at PubMed Central)
DOI: DOI:10.1089/jop.2012.0179   (Journal Full-text)

PURPOSE: Retinal ischemia-associated ocular disorders are vision threatening. This study examined whether the flavonoid baicalein is able to protect against retinal ischemia/reperfusion. METHODS: Using rats, the intraocular pressure was raised to 120 mmHg for 60 min to induce retinal ischemia. In vitro, an ischemic-like insult, namely oxidative stress, was established by incubating dissociated retinal cells with 100 muM ascorbate and 5 muM FeSO4 (iron) for 1 h. The rats or the dissociated cells had been pretreated with baicalein (in vivo: 0.05 or 0.5 nmol; in vitro: 100 muM), vehicle (1% ethanol), or trolox (in vivo: 5 nmol; in vitro: 100 muM or 1 mM). The effects of these treatments on the retina or the retinal cells were evaluated by electrophysiology, immunohistochemistry, terminal deoxynucleotidyl-transferase-mediated dUTP nick end-labeling (TUNEL) staining, Western blotting, or in vitro dichlorofluorescein assay. In addition, real-time-polymerase chain reaction was used to assess the retinal expression of hypoxia-inducible factor-1alpha (HIF-1alpha), matrix metalloproteinase-9 (MMP-9), vascular endothelium growth factor (VEGF), and heme oxygenase-1 (HO-1). RESULTS: The retinal changes after ischemia included a decrease in the electroretinogram b-wave amplitude, a loss of choline acetyltransferase immunolabeling amacrine cell bodies/neuronal processes, an increase in vimentin immunoreactivity, which is a marker for Muller cells, an increase in apoptotic cells in the retinal ganglion cell layer linked to a decrease in the Bcl-2 protein, and changes in the mRNA levels of HIF-1alpha, VEGF, MMP-9, and HO-1. Of clinical importance, the ischemic detrimental effects were concentration dependently and/or significantly (0.05 nmol and/or 0.5 nmol) altered when baicalein was applied 15 min before retinal ischemia. Most of all, 0.5 nmol baicalein significantly reduced the upregulation of MMP-9; in contrast, 5 nmol trolox only had a weak attenuating effect. In dissociated retinal cells subjected to ascorbate/iron, there was an increase in the levels of reactive oxygen species, which had been significantly attenuated by 100 muM baicalein and trolox (100 muM or 1 mM; a stronger antioxidative effect at 1 mM). CONCLUSIONS: Baicalein would seem to protect against retinal ischemia via antioxidation, antiapoptosis, upregulation of HO-1, and downregulation of HIF-1alpha, VEGF, and MMP-9. The antioxidative effect of baicalein would appear to play a minor role in downregulation of MMP-9.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  

Objects Annotated

Genes (Rattus norvegicus)
Hif1a  (hypoxia inducible factor 1 subunit alpha)
Hmox1  (heme oxygenase 1)
Mmp9  (matrix metallopeptidase 9)
Thy1  (Thy-1 cell surface antigen)
Vegfa  (vascular endothelial growth factor A)

Genes (Mus musculus)
Hif1a  (hypoxia inducible factor 1, alpha subunit)
Hmox1  (heme oxygenase 1)
Mmp9  (matrix metallopeptidase 9)
Thy1  (thymus cell antigen 1, theta)
Vegfa  (vascular endothelial growth factor A)

Genes (Homo sapiens)
HIF1A  (hypoxia inducible factor 1 subunit alpha)
HMOX1  (heme oxygenase 1)
MMP9  (matrix metallopeptidase 9)
THY1  (Thy-1 cell surface antigen)
VEGFA  (vascular endothelial growth factor A)


Additional Information