Retinal Ischemia: MMP-9; Its Relation to Resveratrol, Baicalein, S-allyl L-cysteine and Chi Ju Di Huang Wan

Abstract

Ischemia has been reported to be related to matrix metalloproteinase-9 (MMP-9) level upregulation. Neovascular glaucoma (NVG) (in proliferative diabetic retinopathy and central/branch retinal vein occlusion) and age-related macular degeneration are known visionthreatening retinal ischemic disorders. In this review, an extensive discussion has been made into how MMP-9 is related to retinal ischemia and what the underlying mechanisms of various traditional Chinese medicine (TCM) compounds and combinations are. High intraocular pressure-induced retinal ischemic changes were characterized by decreased electroretinogram (ERG) b-wave amplitudes, a loss of choline acetyltransferase (ChAT) immunopositive amacrine neurons/processes, increased Müller's vimentin immunoreactivity, and profound retinal ganglion cell (RGC) death. It has also been observed hypoxia inducible factor-1α (HIF-1α), MMP-9 and vascular endothelium growth factor (VEGF) upregulation at the protein/mRNA levels. After ischemia, both the p38 mitogen-activated protein kinases (MAPKs)-stimulated MMP-9 upregulation and HIF-1α-triggered VEGF overexpression might result in neovascularization. Conclusively, baicalein seems to have neuroprotection via antioxidation, antiapoptosis, HO-1 upregulation and HIF-1α, VEGF, and/or MMP-9 downregulation. Furthermore, baicalein inhibition on retinal ischemia-induced MMP-9 upregulation seems to be "partly" associated with its antioxidation. Additionally, retinal ischemia, oxidative stress, and/or kainate excitotoxicity could be protected by resveratrol: "via MMP-9 and inducible nitric oxide synthetase (iNOS) downregulation, and heme oxygenase-1 (HO-1) upregulation," S-allyl L-cysteine (SAC): "through iNOS, HIF-1α, VEGF inhibition and/or MMP-9 downregulation, and antiapoptosis," Chi Ju Di Huang Wan: "by means of antiapoptosis, antioxidation, MMP-9 downregulation and p38 MAPK inhibition." Keywords: matrix metalloproteinase-9, retinal ischemia, traditional Chinese medicine, hypoxia inducible factor-1α, vascular endothelium growth factor, p38 mitogen-activated protein kinase, baicalein, resveratrol, inducible nitric oxide synthetase, heme oxygenase-1, S-allyl L-cysteine, Chi-Ju-Di-Huang-Wan