Time course of angiogenesis and lymphangiogenesis after brief corneal inflammation

Time course of angiogenesis and lymphangiogenesis after brief corneal inflammation
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DOI:
10.1097/01.ico.0000183485.85636.ff
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发表时间:
2006-05-01
期刊:
影响因子:
2.8
通讯作者:
Kruse, FE
Kruse, FE
中科院分区:
医学3区
文献类型:
--
作者:
Cursiefen, C;Maruyama, K;Kruse, FE

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目的:研究角膜短暂炎症损伤后血管生成和淋巴管生成的时间过程。这可能对高危眼的角膜移植时机有帮助。方法:采用小鼠缝合线诱导炎性角膜新生血管模型。在BALB/c小鼠角膜基质中放置3个中断的11-0缝合线(放置14天)后,于术后2、3、5、7、14、21天以及1、2、3、6、8个月切除角膜。以CD31/PECAM1作为泛内皮细胞,LYVE-1作为淋巴内皮细胞标记物,采用双免疫组化方法评估角膜内皮和淋巴管生成。结果:血管和淋巴管早在缝合后第2天就能进入角膜。结果最初是平行的。哼哼和淋巴管生成在第14天左右达到高峰。此后,两种血管类型开始退化。淋巴管的退化开始得更早,比血管的退化更明显。而在6个月和8个月时(部分)灌注的CD31(+++)/LYVE-1(-)血管和(未灌注的)鬼血管仍可观察到,在此短暂炎症后6个月后,未检测到CD31(+)/LYVE-1(+++)淋巴管。结论:短暂的炎症性角膜损伤后,血管和淋巴管开始平行生长。但此后,淋巴管退化早于血管,6个月后完全退化。病理性角膜淋巴对抗血管的早期消退表明,在炎症性损伤后,高危眼的角膜移植物存活可能最好延迟一段较长的时间。
Purpose: To study the time course of angiogenesis and lymphangiogenesis in the cornea after a short inflammatory insult. This might be helpful for the timing of corneal transplantation in high-risk eyes.Methods: The mouse model of suture-induced inflammatory corneal neovascularization was used. After placement of 3 interrupted 11-0 sutures into the corneal stroma of BALB/c mice (left in place for 14 days), corneas were excised 2, 3, 5, 7, 14, and 21 days as well as 1, 2, 3, 6, and 8 months after surgery. Hem- and lymphangiogenesis were evaluated using double immunohistochemistry of corneas with CD31/PECAM1 as panendothelial and LYVE-1 as lymphatic endothelial marker.Results: Both blood and lymphatic vessels grew into the cornea as early as day 2 after suture placement. The outgrowth was initially parallel. Hem- and lymphangiogenesis peaked around day 14. Thereafter, both vessel types started to regress. Regression of lymphatic vessels started earlier and was more pronounced than that of blood vessels. Whereas at 6 and 8 months (partly) perfused CD31(+++)/LYVE-1(-) blood vessels and (nonperfused) ghost vessels could still be observed, there were no CD31(+)/LYVE-1(+++) lymphatic vessels detectable beyond 6 months after this short inflammation.Conclusions: After a temporary inflammatory insult to the cornea, there is initially parallel outgrowth of both blood and lymphatic vessels. But thereafter, lymphatic vessels regress earlier than blood vessels and are completely regressed by 6 months. Earlier regression of pathologic corneal lymph versus blood vessels suggests that corneal graft survival in high-risk eyes might best be delayed for a prolonged interval following an inflammatory insult.