Molecular mechanisms of ocular angiogenesis and development of therpeutic agents

在糖尿病视网膜病变中，血管屏障破坏、阻塞和新血管形成由任何细胞因子和生长因子引起，包括血管内皮生长因子（VEGF）、转化生长因子-β（TGF-β）超家族和白细胞介素-6（IL-6）。本研究通过检测增殖性糖尿病视网膜病变（proliferative diabetic retinopathy，PDR）患者眼内液及病理性纤维血管组织中VEGF、PIGF、TGF-β超家族（TGF-β，activin A）、白细胞介素-6（IL-6）的表达，探讨其在PDR发病机制中的作用及相互关系。探讨细胞因子/生长因子的表达与糖尿病视网膜病变临床特征的相关性，以了解其在糖尿病视网膜病变发病中的作用。糖尿病视网膜病变患者眼内液中VEGF、PIGE和IL-6浓度升高。在从PDR眼获得的病理性视网膜前增生组织中，VEGF、TGF-β 2和TGF-β 3表达均高于正常视网膜组织。 ...更多信息 激活素A的表达。VEGF浓度与血眼屏障功能及虹膜血管病变程度相关。VEGF被推测在糖尿病视网膜病变中血管屏障功能的破坏和新血管形成中起重要作用。PDR眼中PIGF和VEGF的浓度相关，因为两者都是由缺氧诱导的。血管生成过程受多种生长因子和细胞因子的调节，包括VEGF和TGF-β。下一步，研究VEGF和TGF-β超家族调控血管生成的分子机制、体内血管生成活性以及对体外培养的内皮细胞的影响。激活素A不诱导血管生成。体外对内皮细胞的影响：VEGF刺激血管生成的4个步骤。然而，TGF-β和激活素A在体外抑制内皮细胞功能。这些结果表明，体内和体外的血管生成活性可能是不一致的，因此这两个实验系统是必要的，以评估各种细胞因子的血管生成活性。少

In diabetic retinopathy, vascular barrier breakdown, obstruction and new vessel formation are caused by any cytokines and growth factors, including vascular endothelial growth factor(VEGF), transforming growth factor-beta(TGF-beta)superfamily and interleukin-6(IL-6). The purpose of this presentation is to clarify the roles and the interaction among factors in the pathogenesis of proliferative diabetic retinopathy(PDR).The Expressions of VEGF, PIGF, TGF-beta superfamily(TGF-beta, activin A), interleukin-6(IL-6)in the intraocular humor and the pathological fibrovascular tissues obtained from PDR eyes were investigated. The correlation between the expression of cytokines/growth factors and clinical characteristics was inquired to know the roles in the pathogenesis of diabetic retinopathy. The concentrations of VEGF, PIGE and IL-6 increased in the intraocular humor from diabetic retinopathy eyes. In the pathological preretinal proliferative tissues obtained from PDR eyes, VEGF, TGF-b2, and … More activin A were expressed. The concentration of VEGF, blood-ocular barrier function and pathological changes of iris vessels were correlated. VEGF is speculated to play important roles in the breakdown of vascular barrier functions and new vessel formation in diabetic retinopathy. Concentrations of PIGF and VEGF in PDR eyes were correlated, because both are induced by hypoxia. Activin A counteracted the growth stimulation by VEGF in the cultured endothelial cells.The angiogenesis process is regulated by many growth factors and cytokines including VEGF and TGF-beta. In the next step, to investigate the molecular mechanisms of regulation of angiogenesis, angiogenic activity in vivo and the effects on cultured endothelial cells in vitro of VEGF and TGF-beta superfamily.Angiogenesis in vivo (CAM assay) : VEGF and TGF-beta induced angiogenesis. Activin A did not induce the angiogenesis.Effects on endothelial cells in vitro : VEGF stimulated 4 steps of angiogenesis. However, TGF-beta and activin A inhibited the endothelial cell function in vitro. These results suggest that the angiogenis activity in vivo and that in vitro may be differetnt, so both experimental systems are mandatory to evaluate the angiogenic activity of various cytokines. Less