Analyse the mechanism of choroidal neovascularization (CNV) induced by oxidized LDL receptor and develope the therapy against CNV

1.黄斑下手术中脉络膜新生血管膜中巨噬细胞的聚集。其中一部分是积极的免疫染色抗体对A类清道夫受体（SR-A）是重要的动脉粥样硬化。新生血管膜以外的视网膜相关性黄斑变性也含有SR-A阳性巨噬细胞。清道夫受体可能在脉络膜新生血管形成中起重要作用.在野生型和LOX-1基因敲除（LOX-1 KO）小鼠中制备激光诱导的脉络膜新生血管（CNV）实验模型。LOX-1 mRNA表达在暴露后被诱导。野生型小鼠的前体基质金属蛋白酶（MMPs）蛋白水平升高，MMPs被激活，而LOX-1基因敲除小鼠的MMPs前体蛋白水平降低，MMPs的激活被抑制。在野生型小鼠中，激光照射区域内的新生血管检出率为93%，但在LOX-1基因敲除小鼠中， 关于我们 下降了43%。提示LOX-1可能促进脉络膜新生血管的形成.为了评价给予3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂（匹伐他汀）对CNV的作用，已知匹伐他汀抑制动脉粥样硬化中的高脂血症和斑块形成，在大鼠中建立激光诱导的CNV实验模型。匹伐他汀治疗的大鼠在激光照射区域的荧光泄漏显著减少。匹伐他汀治疗组CNV的面积和厚度均明显低于对照组。这表明治疗剂量的匹伐他汀有效地抑制了大鼠实验性CNV。为了筛选人眼内液中所含的蛋白质，应用蛋白质组学技术对白内障手术中手术切除的眼内液进行双向电泳分析。提取银染蛋白质点，采用基质辅助激光解吸电离飞行时间质谱和数据库检索进行鉴定。白蛋白、别白蛋白、转铁蛋白、载脂蛋白、维生素D结合蛋白、促甲状腺素转移蛋白和抗胰蛋白酶是人房水中的主要蛋白质。

1. Macrophage cells accumulated in choroidal neovascular membranes excised surgically during submacular operation. A portion of them was positively immunostained with antibodies against Class-A scavenger receptors (SR-A) that were important for aterosclerosis. Neovascular membranes other than Age-related macular degeneration also contained SR-A positive macrophage cells. It is possibile that scavenger receptors have an important role for the choroidal neovascularization.2. The experimental models of laser-induced choroidal neovascularization (CNV) were prepared in wild type and LOX-1 gene knockout (LOX-1 KO) mice. The expression of LOX-1 mRNA was induced after exposure. The protein level of precursor matrix metalloproteinases (MMPs) was increased and MMPs were activated in wild mice, but in LOX-1 KO mice, the expression of precursor MMPs and activation of MMPs were suppressed. In wild type mice neovascularity within the laser-exposed area was detected with 93 %, but in LOX-1 KO mice it … More was reduced with 43 %. These data suggest that LOX-1 may promote the choroidal neovascularization.3. To evaluate the effect of the administration of the 3-hydroxy-3-methylglutaryl co-enzyme A(HMG-CoA) reductase inhibitors (pitavastatin) on CNV, that was known to suppress hyperlipidemia and plaque formation in atherosclerosis, the experimental models of laser-induced CNV was created in rats. Pitavastatin-treated rats had significantly less fluorescence leakage in laser-exposed area. Both the area and the thickness of CNV in pitavastatin-treated rais were significantly reduced compared with control. These indicate that the therapeutic dose of pitavastatin effectively suppressed experimental CNV in rats.4. In order to screen the protein cotained in the human intraocular fluid, the proteomics analysis was applied to get the two-dimensional electrophoresis profile; from the aqueous humors excised surgically during cataract operations. The silver-staining protein spots were picked up and identified by matrix-a: sisted laser desorption/ionization time-of-flight mass spectrometry and data base searching. Alubmin, alloalubmin, transferrin, apolipoprotein, vitamin D binding protein, transthretin, and antitrypsin were major proteins in the human aqueous humors Less