State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Cornea. 2012 Sep;31(9):1028-35. doi: 10.1097/ICO.0b013e31823f8b40.
To explore the mechanisms of activated macrophages (A-Mφ) involved in corneal angiogenesis.
Activated macrophages were elicited by mineral oil lumbar injection and implanted into corneal micropockets in rats for the treatment group, A-Mφ, and phosphate-buffered saline group as control. Corneal changes were observed with a slit lamp microscope, and histopathological features were evaluated by immunofluorescence. Reverse transcription-polymerase chain reaction was used to detect the relative expression of angiogenesis-associated factors and inflammatory mediators in the activated macrophages and corneal tissue after implantation.
Immunofluorescence showed that peritoneal cells expressed antigens of cluster of differentiation 68 (CD68, ED1), matrix metalloproteinases-9 (MMP-9), and vascular endothelial growth factor (VEGF). Activated macrophages significantly induced corneal neovascularization (CNV), which peaked on day 5, whereas the control group and normal corneas showed less CNV. The activated macrophages and corneal tissue after implantation expressed the angiogenesis-related factors, such as cyclooxygenase-2, platelet-derived growth factor, transforming growth factor beta, interleukin-1 alpha, MMP-9, and VEGF in messenger RNA (mRNA). However, mRNA expression of MMP-9 and VEGF differed significantly only in the cornea between the A-Mφ group and phosphate-buffered saline group 5 days after the implantation. MMP-9 and VEGF expression of mRNA and protein was higher in the A-Mφ group than that in the control group and normal corneas.
Activated macrophages induce obvious CNV and related mechanisms, which may be correlated with MMP-9 and VEGF autocrine in activated macrophages and upregulation of MMP-9 and VEGF in corneal tissue.
探讨参与角膜血管生成的活化巨噬细胞（A-Mφ）的机制。
通过矿物油腰椎注射诱导活化巨噬细胞，并将其植入大鼠角膜微囊中作为治疗组 A-Mφ，以磷酸盐缓冲盐水组作为对照组。用裂隙灯显微镜观察角膜变化，并通过免疫荧光评估组织病理学特征。在植入后，使用逆转录聚合酶链反应检测活化巨噬细胞和角膜组织中与血管生成相关的因子和炎症介质的相对表达。
免疫荧光显示，腹腔细胞表达分化群 68（CD68、ED1）、基质金属蛋白酶-9（MMP-9）和血管内皮生长因子（VEGF）的抗原。活化巨噬细胞显著诱导角膜新生血管生成（CNV），在第 5 天达到高峰，而对照组和正常角膜的 CNV 较少。植入后的活化巨噬细胞和角膜组织表达与血管生成相关的因子，如环氧化酶-2、血小板衍生生长因子、转化生长因子β、白细胞介素-1α、MMP-9 和 VEGF 的信使 RNA（mRNA）。然而，仅在植入后第 5 天，A-Mφ 组与磷酸盐缓冲盐水组之间，MMP-9 和 VEGF 的 mRNA 表达在角膜中存在显著差异。A-Mφ 组的 MMP-9 和 VEGF 的 mRNA 和蛋白表达均高于对照组和正常角膜。
活化巨噬细胞诱导明显的 CNV 和相关机制，这可能与活化巨噬细胞中的 MMP-9 和 VEGF 自分泌以及角膜组织中 MMP-9 和 VEGF 的上调有关。
