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哥廷根小型猪不适合作为组织工程角膜内皮细胞-载体片的测试和内皮角膜移植的动物模型。

Göttingen Minipig is not a Suitable Animal Model for Testing of Tissue-Engineered Corneal Endothelial Cell-Carrier Sheets and for Endothelial Keratoplasty.

机构信息

Department of Ophthalmology, Aarhus University Hospital , Aarhus, Denmark.

Netherlands Institute for Innovative Ocular Surgery , Rotterdam, The Netherlands.

出版信息

Curr Eye Res. 2020 Aug;45(8):945-949. doi: 10.1080/02713683.2019.1706747. Epub 2020 Jan 6.

Abstract

AIM

To test the feasibility of implanting human anterior lens capsules (HALCs) with porcine corneal endothelial cells (pCEC) in Göttingen minipigs and at the same time test the suitability of Göttingen minipig as model for endothelial keratoplasty.

MATERIALS AND METHODS

Cell-carrier constructs of decellularized HALC with cultured (pCEC) were created for implementation . Eight Göttingen minipigs (6 months old) underwent surgery with descemetorhexis or removal of endothelium by scraping and implementation of HALC without (animal 1-4) and with (animal 5-8) pCEC. Follow-up examinations included optical coherence tomography (OCT) imaging (1,2 and 3 months) and slit-lamp examination (<1 week as well as 1,2 and 3 months).

RESULTS

Intraoperative challenges included difficulties in maintaining an anterior chamber due to soft tissue and vitreous pressure, development of corneal edema and difficulties removing Descemet's membrane because of strong adhesion to stroma. Therefore, descemetorhexis was replaced by mechanical scraping of the endothelium in animal 4-8. HALCs without pCEC were implanted in animal 1-4. Apposition to the back surface was not achieved in animal 1 and 3 because of corneal edema and poor visibility. Animal 5 was sacrificed because of a lens capsule tear. HALCs with pCEC were implanted in animal 6-8. Slit-lamp examination the first week revealed corneal edema in all animals, although mild in animals 4. One-month examination showed retrocorneal membranes with overlying corneal edema in all animals. Histology showed fibrosis in the AC and on the back surface of the cornea, compatible with the clinical diagnosis of retrocorneal membrane.

CONCLUSIONS

In conclusion, the minipig is not suitable for corneal transplantation studies because of intraoperative challenges and development of retrocorneal membrane postoperatively. For testing of the surgical handling and the therapeutic potential of tissue-engineered endothelial cell-carrier constructs other animal models are required.

摘要

目的

测试在哥廷根小型猪中植入人前晶状体囊(HALC)和猪角膜内皮细胞(pCEC)的可行性,同时测试哥廷根小型猪作为内皮角膜移植模型的适用性。

材料和方法

创建了脱细胞 HALC 与培养的(pCEC)细胞载体构建体以进行实施。八只哥廷根小型猪(6 个月大)接受了手术,包括撕除角膜后弹力层或刮除内皮以及植入无(动物 1-4)和有(动物 5-8)pCEC 的 HALC。随访检查包括光学相干断层扫描(OCT)成像(1、2 和 3 个月)和裂隙灯检查(<1 周以及 1、2 和 3 个月)。

结果

术中挑战包括由于软组织和玻璃体压力导致难以维持前房、角膜水肿的发展以及由于与基质的强粘连导致难以去除 Descemet 膜。因此,在动物 4-8 中,用机械刮除内皮代替角膜后弹力层撕除。在动物 1-4 中植入无 pCEC 的 HALC。由于角膜水肿和视力不佳,动物 1 和 3 未能贴合后表面。动物 5 因晶状体囊破裂而被处死。在动物 6-8 中植入了带有 pCEC 的 HALC。所有动物在第一周的裂隙灯检查中均显示角膜水肿,尽管动物 4 的水肿较轻。在一个月的检查中,所有动物均显示后角膜膜伴有角膜水肿。组织学显示房水和角膜后表面有纤维化,与后角膜膜的临床诊断相符。

结论

总之,由于术中挑战和术后后角膜膜的发展,小型猪不适合角膜移植研究。需要其他动物模型来测试手术处理和组织工程内皮细胞载体构建体的治疗潜力。

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