Kinetics of Angiogenic Responses in Corneal Transplantation.
Kinetics of Angiogenic Responses in Corneal Transplantation.
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DOI：
10.1097/ico.0000000000001127
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发表时间：
2017-04
期刊：
影响因子：
2.8
通讯作者：
Dana R
中科院分区：
文献类型：
--
作者：
Inomata T;Mashaghi A;Di Zazzo A;Lee SM;Chiang H;Dana R
描述和比较高危（HR）与低危（LR）角膜移植后角膜血管生成的动力学。在小鼠中，在同种异体移植前两周，将基质内缝线放置在受体移植床上，以诱导血管生成并增加移植物排斥的风险。对照组（LR）移植物受体未进行缝线放置，因此在移植时宿主床保持无血管。通过裂隙灯生物显微镜评价移植物血管生成和混浊评分8周。免疫组化法检测CD 31 hi（血管）和LYVE-1hi（淋巴管）细胞。使用临床和免疫组化评估观察到HR和LR移植受者的血管生成的双相动力学。双相动力学由血管程度的上升-下降（第1阶段）和第二次上升（第2阶段）组成。与LR受体相比，HR受体在8周内表现出更高的血管生成（整个角膜和移植物）。分析移植物显示持续存在的淋巴管在HR受体，然而，淋巴新生血管在LR受体移植后两周消退。与HR宿主床相反，LR宿主床微环境不能维持同种异体移植物中淋巴管新生血管的生长，而它可以维持持续的血管生成。HR宿主床中淋巴管的持续存在可以促进宿主对同种异体移植物的免疫，并且可能与这些移植物长期排斥的持续较高风险相关，这表明在HR角膜移植环境中需要长期持续靶向炎症和淋巴管的治疗干预。
To delineate and compare the kinetics of corneal angiogenesis after high-risk (HR) versus low-risk (LR) corneal transplantation. In mice intrastromal sutures were placed in the recipient graft bed two weeks before allogeneic transplantation to induce angiogenesis and amplify the risk for graft rejection. Control (LR) graft recipients did not undergo suture placement, and thus the host bed remained avascular at the time of transplantation. Graft hemangiogenesis and opacity scores were evaluated for 8 weeks by slit-lamp biomicroscopy. Immunohistochemistry was used to measure CD31hi (blood vessels) and LYVE-1hi (lymphatic vessels) cells. A biphasic kinetics was observed for hemangiogenesis in both HR and LR transplant recipients using clinical and immunohistochemical assessments. The biphasic kinetics was composed of a rise-fall (phase 1) followed by a second rise (phase 2) in the degree of vessels. Compared to LR recipients, HR recipients showed higher hemangiogenesis (whole cornea and graft) throughout 8 weeks. Analyzing grafts revealed sustained presence of lymphatic vessels in HR recipients; however, lymphatic neovessels regressed in LR recipients two weeks post-transplantation. In contrast to HR host beds, the LR host bed microenvironment cannot sustain the growth of lymphatic neovessels in allografts while it can sustain continued hemangiogenesis. The sustained presence of lymphatic vessels in the HR host beds can facilitate host immunity against allografts and is likely associated with ongoing higher risk of rejection of these grafts in long-term, suggesting that therapeutic interventions targeting inflammation and lymphatic vessels need to be sustained long-term in the HR corneal transplant setting.