Abstract
BackgroundRetinal neovascularization is a common cause of vision loss in proliferative diabetic retinopathy, retinopathy of prematurity and age-related macular degeneration. Samul-tang (SMT) is a widely used traditional herbal medicine in East Asia and is also known as Shimotsu-to in Japanese and Si-Wu decoction in Chinese. This study was designed to evaluate the inhibitory effect of SMT on retinal pathogenic angiogenesis in a mouse model of oxygen-induced retinopathy (OIR).MethodThe mice were exposed to a 75 % concentration of oxygen for five days, starting on postnatal day 7 (P7-P12). The mice were then exposed to room air and were intraperitoneally injected with SMT (10 mg/kg or 50 mg/kg) once per day for five days (P12-P16). On P17, we measured retinal neovascularization and evaluated both the expression of angiogenesis-related proteins and changes in the gene expression level in the mRNA.ResultsSMT reduced the area of the central retina and reduced retinal neovascularization in OIR mice. The protein array revealed that SMT reduced the level of SDF-1 protein expression. Quantitative real-time PCR revealed that the HIF-1α, SDF-1, CXCR4 and VEGF mRNA levels in the retinas of OIR mice were elevated compared with those of normal control mice. However, SMT decreased the levels of HIF-1α, SDF-1, CXCR4 and VEGF mRNA in OIR mice.ConclusionWe are the first to elucidate that SMT inhibits the retinal pathogenic angiogenesis induced by ischemic retinopathy in OIR mice. SMT significantly inhibited retinal neovascularization by downregulating HIF-1α, SDF-1, CXCR4 and VEGF. Based on the results of our study, SMT could be a useful herbal medicine for treating ischemic retinopathy.
Highlights
Retinal neovascularization is a common cause of vision loss in proliferative diabetic retinopathy, retinopathy of prematurity and age-related macular degeneration
Quantitative real-time PCR revealed that the Hypoxia inducible factor (HIF)-1α, stromal cell-derived factor 1 (SDF-1), CXCR4 and Vascular endothelial growth factor (VEGF) mRNA levels in the retinas of oxygen-induced retinopathy (OIR) mice were elevated compared with those of normal control mice
We are the first to elucidate that SMT inhibits the retinal pathogenic angiogenesis induced by ischemic retinopathy in OIR mice
Summary
Retinal neovascularization is a common cause of vision loss in proliferative diabetic retinopathy, retinopathy of prematurity and age-related macular degeneration. This study was designed to evaluate the inhibitory effect of SMT on retinal pathogenic angiogenesis in a mouse model of oxygen-induced retinopathy (OIR). Proliferative diabetic retinopathy, retinopathy of prematurity and age-related macular degeneration are the most common causes of retinal neovascularization [1, 2]. Vascular endothelial growth factor (VEGF) plays a central pathogenic role in retinal neovascularization caused by hypoxia-induced retinal damage. The disruption of VEGF signaling is a useful target for therapeutic interventions, and VEGF antagonists have an inhibitory effect on angiogenesis [6]. All anti-VEGF therapies require repeated injections of expensive VEGF antagonists and only offer a temporary respite from vascular leakage; such therapies can achieve only partial clinical success. The lack of efficacy of anti-VEGF treatments may be caused by the effects of this treatment on the HIF pathway-mediated expression of other
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