Antiangiogenic Effects of E1E4^+ and E1^-E4^-Adenoviral Vectorsand Its Possible Mechanism

E1E4^和E1^-E4^-腺病毒载体的抗血管生成作用及其可能机制

• 批准号: 14571685
• 负责人: MORI Keisuke
• 金额: $ 2.18万
• 依托单位: Saitama Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571685/
• 关键词: adenoviral vector; angiogenesis; microarray; neuroprotection; 血管新生抑制作用; early region 4

The purpose of this study is to identify the genes which are up-or down-regulated by intraocular injection of both El, E3 deleted and El, E3, E4 deleted adenoviral vectors. Adenoviral vectors are intravitreously injected to mice eyes and then mRNA expression was screened by cDNA or oligonucleotide microarray. Animals are divided into 2 categories ; one is normal untreated mice, and the other is mice with oxygen-induced ischemic retinopathy. For the mice model of ischemic retinopathy mice were housed in 75% oxygen from P7 to P12. Viral vectors were injected Pl0 and eyes were enucleated P13.In normal eyes with GVl0 injection 580 genes were up or down regulated, when compared to eyes without vector injection among 12,422 probesets and ESTs. Also, in normal eyes with GV11 injection 660 genes were up or down regulated, when compared to eyes without vector injection. These were also tested in mice eyes with ischemic retinopathy and found totally 60 genes were up-or down-regulated. Among these genes MHC class I antigen is one of the aniogenesis related gene. There were some more candidate genes to screen out their function.

本研究的目的是鉴定眼内注射El， E3缺失和El， E3， E4缺失腺病毒载体上调或下调的基因。将腺病毒载体静脉注射到小鼠眼内，用cDNA或寡核苷酸芯片筛选mRNA表达。动物分为两类；一组是正常小鼠，另一组是氧致缺血性视网膜病变小鼠。对于缺血性视网膜病变小鼠模型，将小鼠置于75%氧气环境中，从P7到P12。将病毒载体注入p0，将P13去核。在12422个测试集和ESTs中，与未注射载体的眼睛相比，注射GVl0的正常眼睛中有580个基因上调或下调。此外，与未注射载体的眼睛相比，在注射GV11的正常眼睛中，660个基因被上调或下调。这些基因也在患有缺血性视网膜病变的小鼠眼睛中进行了测试，发现总共有60个基因被上调或下调。在这些基因中，MHC I类抗原是与胚胎发生相关的基因之一。还有更多的候选基因来筛选它们的功能。

项目成果

Imai D, et al.: "Intraocular gene transfer of pigment epithelium-derived factor rescues photoreceptors from light-induced cell death."J Cell Physiol. (in press).

Imai D 等人：“色素上皮衍生因子的眼内基因转移可将光感受器从光诱导的细胞死亡中拯救出来。”J Cell Physiol。

Takita H, et al.: "Retinal neuroprotection against ischemic injury mediated by intraocular gene transfer of pigment epithelium-derived factor."Invest Ophthalmol Vis Sci. 44. 4497-4504 (2003)

Takita H 等人：“通过色素上皮衍生因子的眼内基因转移介导的视网膜神经保护以防止缺血性损伤。”Invest Ophasemol Vis Sci。

Imai D, et al.: "Intraocular gene transfer of pigment epithelium-derived factor rescues photoreceptors from light-induced cell death."Journal of Cellular Physiology. (in press).

Imai D 等人：“色素上皮衍生因子的眼内基因转移可将光感受器从光诱导的细胞死亡中拯救出来。”细胞生理学杂志。