Attenuation of streptozotocin-induced diabetic retinopathy with low molecular weight fucoidan via inhibition of vascular endothelial growth factor

	Attenuation of streptozotocin-induced diabetic retinopathy with low molecular weight fucoidan via inhibition of vascular endothelial growth factor
	Yang, Wenzhe 1; Yu, Xinfeng 1; Zhang, Quanbin 2; Lu, Qingjun 3; Wang, Jing2 ; Cui, Wentong 1; Zheng, Yuanyuan 1; Wang, Xiaomin 4; Luo, Dali 1
刊名	EXPERIMENTAL EYE RESEARCH
	2013-10-01
卷号	115 页码:96-105
关键词	low molecular weight fucoidan diabetic retinopathy vascular endothelial growth factor vascular endothelial cells high glucose hypoxia-inducible factor-1 alpha
ISSN号	0014-4835
通讯作者	Luo, DL
中文摘要	Diabetic retinopathy (DR) is a hyperglycemia-induced ischemic disorder characterized by microvascular dysfunction and neovascularization. It is a leading cause of blindness in many countries, yet efficient drugs are limited now for prevention and treatment of DR. Low molecular weight fucoidan (LMWF), extract from brown algae, has been shown to possess multiple biological activities like anti-inflammation, anti-oxidation and anti-aggregation, which all could be beneficial for attenuating ischemia-induced tissue damages. Here, by comparing with calcium dobesilate, the potent antioxidant compound currently used for the treatment of DR, we investigated the protective effect of LMWF against DR in streptozotocin-induced diabetic mice and high glucose-promoted vascular endothelial growth factor (VEGF) production and cell proliferation in microvascular endothelial cells. One week after diabetes induction, the mice were administered with LMWF (50, 100 or 200 mg/kg/day) or calcium dobesilate (200 mg/kg/day) for four months, then the retinal pathological changes and neovascularization were detected by hematoxylin-eosin staining and fluorescein dextran angiography, respectively. Immunofluorescence staining, ELISA and RT-PCR were used to examine the expression levels of hypoxia-inducible factor-1 alpha (HIF-1 alpha) and VEGF in retina and endothelial cells. Here, we found that LMWF resembled calcium dobesilate, in alleviating retinal pathological change and hindering neovascularization due to diabetes in vivo. The relative levels of VEGF expression and HIF-1 alpha induction were also less in retinas of LMWF- or calcium dobesilate-treated diabetic mice than those in retinas of control mice. Furthermore, high glucose-induced VEGF overexpression and cell proliferation in primary cultured vascular endothelial cells were also inhibited by LMWF in a dose-dependent manner. Therefore, this study demonstrated that LMWF alleviates diabetic retinal neovascularization and damage likely through lowering HIF-1 alpha and VEGF expressions, providing a potential candidate drug for prevention and treatment of diabetic retinopathy. (C) 2013 Elsevier Ltd. All rights reserved.
英文摘要	Diabetic retinopathy (DR) is a hyperglycemia-induced ischemic disorder characterized by microvascular dysfunction and neovascularization. It is a leading cause of blindness in many countries, yet efficient drugs are limited now for prevention and treatment of DR. Low molecular weight fucoidan (LMWF), extract from brown algae, has been shown to possess multiple biological activities like anti-inflammation, anti-oxidation and anti-aggregation, which all could be beneficial for attenuating ischemia-induced tissue damages. Here, by comparing with calcium dobesilate, the potent antioxidant compound currently used for the treatment of DR, we investigated the protective effect of LMWF against DR in streptozotocin-induced diabetic mice and high glucose-promoted vascular endothelial growth factor (VEGF) production and cell proliferation in microvascular endothelial cells. One week after diabetes induction, the mice were administered with LMWF (50, 100 or 200 mg/kg/day) or calcium dobesilate (200 mg/kg/day) for four months, then the retinal pathological changes and neovascularization were detected by hematoxylin-eosin staining and fluorescein dextran angiography, respectively. Immunofluorescence staining, ELISA and RT-PCR were used to examine the expression levels of hypoxia-inducible factor-1 alpha (HIF-1 alpha) and VEGF in retina and endothelial cells. Here, we found that LMWF resembled calcium dobesilate, in alleviating retinal pathological change and hindering neovascularization due to diabetes in vivo. The relative levels of VEGF expression and HIF-1 alpha induction were also less in retinas of LMWF- or calcium dobesilate-treated diabetic mice than those in retinas of control mice. Furthermore, high glucose-induced VEGF overexpression and cell proliferation in primary cultured vascular endothelial cells were also inhibited by LMWF in a dose-dependent manner. Therefore, this study demonstrated that LMWF alleviates diabetic retinal neovascularization and damage likely through lowering HIF-1 alpha and VEGF expressions, providing a potential candidate drug for prevention and treatment of diabetic retinopathy. (C) 2013 Elsevier Ltd. All rights reserved.
学科主题	Ophthalmology
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Ophthalmology
研究领域[WOS]	Ophthalmology
关键词[WOS]	CALCIUM DOBESILATE ; EYE DISEASE ; EXPRESSION ; CELLS ; ANGIOGENESIS ; RATS ; POLYSACCHARIDES ; PROLIFERATION ; MODULATION ; MIGRATION
收录类别	SCI
原文出处	10.1016/j.exer.2013.06.011
语种	英语
WOS记录号	WOS:000326060600013
公开日期	2014-07-17
内容类型	期刊论文
源URL	[http://ir.qdio.ac.cn/handle/337002/16685]
专题	海洋研究所_海洋生物技术研发中心
作者单位	1.Capital Med Univ, Sch Chem Biol & Pharmaceut Sci, Dept Pharmacol, Beijing 100069, Peoples R China 2.Chinese Acad Sci, Inst Oceanol, Qingdao 266071, Peoples R China 3.Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Beijing Ophthalmol & Visual Sci Key Lab, Beijing, Peoples R China 4.Capital Med Univ, Dept Physiol, Beijing 100069, Peoples R China
推荐引用方式 GB/T 7714	Yang, Wenzhe,Yu, Xinfeng,Zhang, Quanbin,et al. Attenuation of streptozotocin-induced diabetic retinopathy with low molecular weight fucoidan via inhibition of vascular endothelial growth factor[J]. EXPERIMENTAL EYE RESEARCH,2013,115:96-105.
APA	Yang, Wenzhe.,Yu, Xinfeng.,Zhang, Quanbin.,Lu, Qingjun.,Wang, Jing.,...&Luo, Dali.(2013).Attenuation of streptozotocin-induced diabetic retinopathy with low molecular weight fucoidan via inhibition of vascular endothelial growth factor.EXPERIMENTAL EYE RESEARCH,115,96-105.
MLA	Yang, Wenzhe,et al."Attenuation of streptozotocin-induced diabetic retinopathy with low molecular weight fucoidan via inhibition of vascular endothelial growth factor".EXPERIMENTAL EYE RESEARCH 115(2013):96-105.