Department of Ophthalmology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Jiangsu Key Laboratory of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Mol Med Rep. 2018 Nov;18(5):4388-4398. doi: 10.3892/mmr.2018.9445. Epub 2018 Sep 3.
The present study aimed to investigate the effects of diabetes mellitus (DM) on the generation of experimental corneal neovascularization (CrNV) and choroidal neovascularization (ChNV). Diabetes was induced in mice by intraperitoneal injection of streptozotocin (STZ). Experimental CrNV and ChNV were induced by alkali injury and laser photocoagulation, respectively. CrNV and ChNV were compared between the STZ‑induced diabetic mice and control mice two weeks after injury. Relative expression of angiogenic factors was quantified by reverse transcription‑quantitative polymerase chain reaction, and progenitor cell or macrophage accumulation in the early phase following injury was examined by flow cytometric analysis. Compared with the alkali‑injured normal mice, the alkali‑injured diabetic mice (STZ‑induced) exhibited no significant difference in CrNV occurrence, whereas the laser‑injured diabetic mice exhibited significantly reduced levels of ChNV compared with those of the laser‑injured control animals. The laser‑induced intrachoroidal mRNA expression levels of angiogenic factors, including vascular endothelial growth factor, hypoxia‑induced factor‑1α, chemokine (C‑C motif) ligand 3, and stromal cell‑derived factor‑1α, were reduced in the laser‑injured diabetic mice when compared with laser‑injured control mice. Furthermore, the laser‑induced intrachoroidal infiltration of c‑Kit+ progenitor cells was impaired in the laser‑injured diabetic mice compared with the laser‑injured control mice. Overall, diabetes did not exert a significant effect on the generation of experimental CrNV. However, diabetes reduced laser‑induced ChNV through downregulation of intrachoroidal progenitor cell infiltration and angiogenic factor expression.
本研究旨在探讨糖尿病(DM)对实验性角膜新生血管(CrNV)和脉络膜新生血管(ChNV)形成的影响。通过腹腔注射链脲佐菌素(STZ)诱导小鼠发生糖尿病。通过碱烧伤和激光光凝分别诱导实验性 CrNV 和 ChNV。在损伤后两周比较 STZ 诱导的糖尿病小鼠和对照小鼠的 CrNV 和 ChNV。通过反转录定量聚合酶链反应定量分析血管生成因子的相对表达,通过流式细胞术分析损伤后早期祖细胞或巨噬细胞的积累。与正常小鼠碱烧伤相比,碱烧伤糖尿病小鼠(STZ 诱导)的 CrNV 发生无显著差异,而激光烧伤糖尿病小鼠的 ChNV 水平明显低于激光烧伤对照组。与激光烧伤对照组相比,激光诱导的脉络膜内血管生成因子(包括血管内皮生长因子、缺氧诱导因子-1α、趋化因子(C-C 基序)配体 3 和基质细胞衍生因子-1α)的 mRNA 表达水平降低。此外,与激光烧伤对照组相比,激光烧伤糖尿病小鼠的脉络膜内 c-Kit+祖细胞浸润受损。总之,糖尿病对实验性 CrNV 的形成没有显著影响。然而,糖尿病通过下调脉络膜内祖细胞浸润和血管生成因子表达,减少了激光诱导的 ChNV。