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

本研究的目的是鉴定通过眼内注射E1，E3缺失和E1，E3，E4缺失的腺病毒载体上调或下调的基因。将腺病毒载体玻璃体内注射到小鼠眼内，然后通过cDNA或寡核苷酸芯片筛选mRNA表达。将动物分为2类;一类是正常的未处理小鼠，另一类是具有氧诱导的缺血性视网膜病变的小鼠。对于缺血性视网膜病变的小鼠模型，从P7至P12将小鼠圈养在75%氧气中。P10时注射病毒载体，P13时去核。在12，422个探针和EST中，注射GV 10的正常眼与未注射载体的眼相比，有580个基因表达上调或下调。此外，与未注射载体的眼睛相比，在注射GV 11的正常眼睛中，660个基因上调或下调。这些基因也在缺血性视网膜病变的小鼠眼中进行了测试，共发现60个基因表达上调或下调。在这些基因中，MHC I类抗原是与动物发生相关的基因之一。还有一些候选基因可以筛选出它们的功能。

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.