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血管内皮生长因子抑制剂康柏西普对兔穿透性角膜移植术后角膜新生血管形成的影响

Effects of VEGF Inhibitor Conbercept on Corneal Neovascularization Following Penetrating Keratoplasty in Rabbit Model.

作者信息

Liu Huan, Zhang Xiao-Rong, Xu Hong-Chang, Ma Yue, Huang Li-Ying, Zhai Li-Ying, Zhao Ying

机构信息

Division of Ocular Injuries, Department of Ophthalmology, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.

Hebei OPO Eye Bank, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.

出版信息

Clin Ophthalmol. 2020 Jul 31;14:2185-2193. doi: 10.2147/OPTH.S260302. eCollection 2020.

DOI:10.2147/OPTH.S260302
PMID:32801629
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7410491/
Abstract

PURPOSE

To evaluate the effects of the vascular endothelial growth factor inhibitor conbercept (KH902) on corneal neovascularization and wound healing following penetrating keratoplasty in rabbits.

METHODS

Conbercept was administered to New Zealand white rabbits through topical and subconjunctival routes. Corneal neovascularization and wound healing were examined by slit-lamp photography and histological analyses. The expressions of vascular endothelial growth factor inhibitor, α-smooth muscle actin, and keratocan in the corneal grafts were measured by real-time quantitative polymerase chain reaction (RT-qPCR).

RESULTS

The anterior segment photographs demonstrated that corneal neovascularization started in the 2nd week. In the 4th week, histologically, the superficial corneal stroma layer showed disordered arrangement, and there were large numbers of dense inflammatory cells and blood vessels in the stroma layer. Vascular endothelial growth factor in the experimental groups was significantly decreased at all time points compared with the control group (both P = 0.001). Expression of α-smooth muscle actin in corneal grafts demonstrated an increase in time even it was lower in experimental groups, but the difference was not statistically significant (P equaled to 0.507 and 0.723, respectively). There were no significant differences with the expression of keratocan in all groups except that it significantly declined at the 4th week as to the second week in all groups and P values were 0.022, 0.020 and 0.014 in control (C), topical (E1), and subconjunctival (E2) group, respectively.

CONCLUSION

The study found that conbercept inhibited the formation of corneal neovascularization without affecting keratocan-mediated corneal wound healing and there were no significant differences between topical administration of different doses of conbercept on the rabbit corneal neovascularization after penetrating keratoplasty in this study.

摘要

目的

评估血管内皮生长因子抑制剂康柏西普(KH902)对兔穿透性角膜移植术后角膜新生血管形成及伤口愈合的影响。

方法

通过局部和结膜下途径给新西兰白兔施用康柏西普。通过裂隙灯摄影和组织学分析检查角膜新生血管形成及伤口愈合情况。采用实时定量聚合酶链反应(RT-qPCR)检测角膜移植物中血管内皮生长因子抑制剂、α-平滑肌肌动蛋白和角蛋白聚糖的表达。

结果

眼前节照片显示角膜新生血管在第2周开始出现。在第4周,组织学检查显示角膜浅基质层排列紊乱,基质层中有大量密集的炎性细胞和血管。与对照组相比,各时间点实验组的血管内皮生长因子均显著降低(P均=0.001)。角膜移植物中α-平滑肌肌动蛋白的表达随时间增加,尽管实验组较低,但差异无统计学意义(P分别等于0.507和0.723)。除第4周时所有组的角蛋白聚糖表达均较第2周显著下降外,各组之间角蛋白聚糖表达无显著差异,对照组(C)、局部给药组(E1)和结膜下给药组(E2)的P值分别为0.022、0.020和0.014。

结论

本研究发现康柏西普可抑制角膜新生血管形成,且不影响角蛋白聚糖介导的角膜伤口愈合,本研究中不同剂量康柏西普局部给药对兔穿透性角膜移植术后角膜新生血管形成的影响无显著差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7bb/7410491/aeb97b55cb94/OPTH-14-2185-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7bb/7410491/d4272d29a7a5/OPTH-14-2185-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7bb/7410491/b7066cbaedf6/OPTH-14-2185-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7bb/7410491/f1d6a62c7c1d/OPTH-14-2185-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7bb/7410491/848041a6030a/OPTH-14-2185-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7bb/7410491/aeb97b55cb94/OPTH-14-2185-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7bb/7410491/d4272d29a7a5/OPTH-14-2185-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7bb/7410491/b7066cbaedf6/OPTH-14-2185-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7bb/7410491/f1d6a62c7c1d/OPTH-14-2185-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7bb/7410491/848041a6030a/OPTH-14-2185-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7bb/7410491/aeb97b55cb94/OPTH-14-2185-g0005.jpg

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