IKK2阻滞剂对脉络膜新生血管膜抑制作用的研究

Choroidal neovascularization (CNV, choroidal neovascularizat ion) is a key factor to induce age-related macular degeneration, centrality with choroid retinopathy, high myopia and some other retinal disease which can finally cause the vision loss. Studies showing that NF - kB play an important role to regulate the activation of endothelial cell and the formation of new blood vessels in the retina. IKK2 also have an important role for the NF - kB pathways. Our previous studies found that the growth of new blood vessels in choroidal neovascularization membrane was inhibited in IKK2 knockout mice under.Importantly, the inhibition effect is higher than the clinical drug Lucentis and also is more safety. As IKK2 is important for the growth of CNV, future study will use laser induced mice choroidal neovascularization animal model and the IKK2 inhibitor together with the angiography, choroidal stretched immunohistochemical techniques to detect the inhibition effect of IKK2 inhibitor on the choroidal neovascularization, and using molecular and cellular biology methods to elucidate the possible mechanism. Finally, using OKR and flow cytometry to detect the toxicity effects on visual function which can provide theoretical support and technical guidance for clinical production of new drugs.

脉络膜新生血管(choroidal neovascularization, CNV )是导致年龄相关性黄斑变性等多种眼底疾病视力丧失的主要原因。有研究指出NF-kB 介导的炎症传导通路参与视网膜新生血管的形成。IKK2是NF-kB信号通路中的重要调控蛋白。课题前期实验已证实，IKK2基因敲除小鼠的脉络膜下新生血管膜的生长明显受到抑制,其阻断效率及安全性均优于先临床用药Lucentis。由于IKK2对CNV的生长起主要的调控作用。本课题将采用激光诱发的小鼠脉络膜新生血管的动物模型，眼局部IKK2阻滞剂给药后，通过眼底造影、脉络膜铺片、免疫组化技术等观察IKK2阻滞剂对脉络膜新生血管膜的抑制作用；通过分子生物学技术研究体内及细胞水平上的相关变化，阐明IKK2阻滞剂抑制CNV可能的机制；并通过OKR及流式细胞术研究药物对视功能及全身毒副作用；为临床新药的开发提供理论支持及技术指导

项目背景：脉络膜新生血管( choroidal neovascularizat ion, CNV )是导致年龄相关性黄斑变性、中心性渗出性脉络膜视网膜病变和高度近视等多种眼底疾病视力丧失的主要原因。临床目前虽然已有多种治疗方法，但价格昂贵且治疗效果不尽人意，因此寻找致病机制及有效治疗方法成为当务之急。.主要研究内容：新近研究指出NF-kB 在血管内皮细胞的激活中起重要的作用，参与视网膜新生血管的形成。IKK2是NF-kB作用途径上重要的调控步骤。可能成为预防和治疗脉络膜新生血管的新靶点，而推动抑制脉络膜新生血管新药的开发。课题前期实验已证实，IKK2基因敲除小鼠的脉络膜下新生血管膜的生长受到抑制,说明IKK2在脉络膜新生血管膜的生长过程并起到明显的调控作用,阻滞此基因可明显抑制脉络膜新生血管的生长。.重要结果：本课题采用激光诱发的小鼠脉络膜新生血管的动物模型，通过免疫组化、分子生物学技术研究IKK2阻滞剂对脉络膜新生血管膜抑制作用的机制，并采用多种眼局部用药，寻找到安全有效给药途径，为临床新药物的产生提供理论、技术指导。.重要结果：本课题发表SCI收录文章5篇，培养硕士研究生2名，博士研究生2名。