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一项关于兔眼房内注射苯扎氯铵效果的剂量递增体外研究。

A dose-escalation ex vivo study on the effects of intracameral benzalkonium chloride in rabbits.

作者信息

Segarra Sergi, Leiva Marta, Costa Daniel, Coyo Natàlia, Sabés-Alsina Maria, Ríos José, Peña Teresa

机构信息

Departament de Medicina i Cirurgia Animals, Facultat de Veterinària, Bellaterra, Spain.

Fundació Hospital Clínic Veterinari, UAB, Bellaterra, Spain.

出版信息

BMC Vet Res. 2018 Feb 2;14(1):39. doi: 10.1186/s12917-018-1349-8.

DOI:10.1186/s12917-018-1349-8
PMID:29394897
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5796406/
Abstract

BACKGROUND

Rabbits are currently not a good model for studying diseases of the corneal endothelium because their corneal endothelial cells (CECs) maintain a high proliferative capacity throughout almost all their life. Addressing this particular feature might allow the use of this species for such a purpose. The aim of this study was to evaluate the corneal endothelial injury after intracameral benzalkonium chloride (BAC) injection into rabbit eyes ex vivo, and to establish the most suitable starting dose for an in vivo study aimed at developing an animal model of corneal endothelial disease.

RESULTS

Forty rabbit eyes obtained postmortem by transconjunctival enucleation were divided into 8 groups according to the injected compound: Control (no injection), BSS, and increasing BAC concentrations (0.005%, 0.01%, 0.025%, 0.05%, 0.1% and 0.2%). At 0, 6, 24 and 48 h, ophthalmologic examination of the anterior segment, pachymetry and specular microscopy were performed, and corneas were finally vital-stained and observed under the light microscope to assess the CECs morphology and mortality rate. When compared to BSS, CECs density started to decrease significantly at 0.025% BAC concentration, while mean cell area, corneal edema and corneal thickness began to increase significantly at 0.05%, 0.005% and 0.1% BAC concentrations, respectively. Concentrations of 0.05% BAC and above caused significant increases in CECs pleomorphism (decreased hexagonality) and mortality, compared to control and BSS.

CONCLUSIONS

Ex vivo intracameral BAC injection induces corneal endothelial toxicity in rabbits. However, confirmatory in vivo studies are required to develop the desired model, with 0.05% BAC being a suggested starting point.

摘要

背景

兔子目前并非研究角膜内皮疾病的理想模型,因为其角膜内皮细胞(CECs)在几乎整个生命周期内都保持着较高的增殖能力。解决这一特殊特征可能会使该物种适用于此目的。本研究的目的是评估离体兔眼前房注射苯扎氯铵(BAC)后的角膜内皮损伤,并确定旨在建立角膜内皮疾病动物模型的体内研究的最合适起始剂量。

结果

通过经结膜眼球摘除术死后获取的40只兔眼,根据注射的化合物分为8组:对照组(未注射)、平衡盐溶液(BSS)以及BAC浓度递增组(0.005%、0.01%、0.025%、0.05%、0.1%和0.2%)。在0、6、24和48小时,进行眼前节眼科检查、角膜测厚和角膜内皮显微镜检查,最后对角膜进行活体染色并在光学显微镜下观察,以评估CECs的形态和死亡率。与BSS相比,CECs密度在BAC浓度为0.025%时开始显著下降,而平均细胞面积、角膜水肿和角膜厚度分别在BAC浓度为0.05%、0.005%和0.1%时开始显著增加。与对照组和BSS相比,0.05%及以上的BAC浓度导致CECs多形性(六边形减少)和死亡率显著增加。

结论

离体前房注射BAC可诱导兔角膜内皮毒性。然而,需要进行确证性的体内研究来建立所需模型,0.05%的BAC是建议的起始点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d11/5796406/4932a5d4366b/12917_2018_1349_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d11/5796406/91e56baccb6b/12917_2018_1349_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d11/5796406/eadda85ef0b0/12917_2018_1349_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d11/5796406/a1b5528099f0/12917_2018_1349_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d11/5796406/4932a5d4366b/12917_2018_1349_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d11/5796406/91e56baccb6b/12917_2018_1349_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d11/5796406/eadda85ef0b0/12917_2018_1349_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d11/5796406/a1b5528099f0/12917_2018_1349_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d11/5796406/4932a5d4366b/12917_2018_1349_Fig4_HTML.jpg

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