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鸡角膜基质内植入物对兔角膜增厚的影响:一项实验研究。

Intrastromal implantation of chicken corneal grafts into the cornea of rabbits for corneal thickening: an experimental study.

机构信息

Provisão Hospital de Olhos de Maringá, Rua Silva Jardim, Nº 359, Maringá, 87013-010, Brazil.

Santa Casa de São Paulo Medical School, Rua Dr. Cesário Mota Junior, 112 - Vila Buarque, São Paulo, 01221-020, Brazil.

出版信息

Int Ophthalmol. 2021 Jan;41(1):243-255. doi: 10.1007/s10792-020-01573-4. Epub 2020 Aug 26.

DOI:10.1007/s10792-020-01573-4
PMID:32845463
Abstract

PURPOSE

To evaluate the feasibility and effects of the intrastromal implantation of chemically modified corneal stroma obtained from chicken into the corneas of rabbits for corneal thickening.

METHODS

Chicken corneas were cut, debrided, treated with cross-linking and implanted in an intrastromal pouch created in the cornea of 10 white New Zealand rabbits with femtosecond laser. Slit-lamp biomicroscopy and optical coherence tomography were performed immediately, 7, 30 and 90 days postoperatively. Corneas were removed at 90 days and cut in two halves. One half was sent to histological analysis for the presence of necrosis, polymorphonuclear inflammatory cells, blood vessels and fibrosis, while the other half was evaluated with transmission electron microscopy to verify tissue organization and the presence of keratocytes and inflammatory cells. Corneal thicknesses were comparatively analyzed over time with Wilcoxon test (p ≤ 0.05).

RESULTS

The chicken grafts were incorporated into the cornea of all animals over time. Mean rabbit cornea thickness increased from 338 µm preoperatively to 538 µm (p < 0.0077) at 90 days, while mean chicken graft thickness decreased from 350 to 215 µm (p < 0.0077). No clear signs of rejection attributable to the xenograft were observed in any of the implanted eyes. However, some macroscopic and histological events were observed in some of the eyes, probably due to procedural issues during implantation.

CONCLUSION

The intrastromal implantation of chicken grafts was shown to be feasible and predictable to thicken the recipient rabbit cornea without apparent rejection. However, before being considered in humans, further meticulous clinical trials are required to establish the clinical utility, safety and efficacy of xenografts for the treatment of patients with advanced keratoconus.

摘要

目的

评估将鸡角膜基质经化学改性后植入兔角膜内以增加角膜厚度的可行性和效果。

方法

用飞秒激光在 10 只新西兰白兔角膜内制作基质内囊袋,将鸡角膜切开、清创、交联后植入其中。术后即刻、7 天、30 天和 90 天进行裂隙灯生物显微镜和光学相干断层扫描检查。术后 90 天处死动物并取角膜,沿垂直角膜缘将其分为两半。一半用于组织学分析,检查有无坏死、多形核炎性细胞、血管和纤维化;另一半用于透射电镜检查,观察组织学结构以及是否存在角膜细胞和炎性细胞。采用 Wilcoxon 检验比较不同时间点的角膜厚度(p≤0.05)。

结果

随时间推移,鸡移植物逐渐被兔角膜整合。所有动物的兔眼角膜平均厚度从术前的 338µm 增加到术后 90 天的 538µm(p<0.0077),而鸡移植物平均厚度从 350µm 降至 215µm(p<0.0077)。未观察到明显与异种移植物排斥相关的排斥迹象。然而,一些植入眼出现了一些宏观和组织学事件,可能与植入过程中的操作问题有关。

结论

将鸡移植物间质内植入兔角膜可增加受体角膜厚度,且无明显排斥反应,具有可行性和可预测性。然而,在考虑将其应用于人类之前,需要进行进一步的、精心设计的临床试验,以确定异种移植物治疗晚期圆锥角膜患者的临床实用性、安全性和疗效。

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本文引用的文献

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3D bioprinting for artificial cornea: Challenges and perspectives.三维生物打印人工角膜:挑战与展望。
Med Eng Phys. 2019 Sep;71:68-78. doi: 10.1016/j.medengphy.2019.05.002. Epub 2019 Jun 11.
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Small Incision Femtosecond Laser-assisted X-ray-irradiated Corneal Intrastromal Xenotransplantation in Rhesus Monkeys: A Preliminary Study.恒河猴小切口飞秒激光辅助 X 射线辐照角膜间充质异种移植:初步研究。
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Corneal Xenotransplantation From Pig to Rhesus Monkey: No Signs of Transmission of Endogenous Porcine Retroviruses.从猪到恒河猴的角膜异种移植:无内源性猪逆转录病毒传播迹象
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Viability of homologous and heterologous subcutaneous transplantation of fresh germ cells in rabbits.兔新鲜生殖细胞同种和异种皮下移植的可行性
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Cellular Therapy With Human Autologous Adipose-Derived Adult Stem Cells for Advanced Keratoconus.采用人自体脂肪来源的成体干细胞进行细胞治疗晚期圆锥角膜
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