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瑞巴派特可预防兔青光眼滴眼液诱导的眼表疾病。

Rebamipide protects against glaucoma eyedrop-induced ocular surface disorders in rabbits.

作者信息

Kawaguchi Ichiro, Kobayashi Akira, Higashide Tomomi, Takeji Yasuhiro, Sakurai Kazushi, Kawaguchi Chiaki, Sugiyama Kazuhisa

机构信息

Department of Ophthalmology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.

Otsuka Pharmaceutical Co., Ltd, Ako Research Institute, Ako, Hyogo, Japan.

出版信息

PLoS One. 2017 Oct 19;12(10):e0186714. doi: 10.1371/journal.pone.0186714. eCollection 2017.

DOI:10.1371/journal.pone.0186714
PMID:29049370
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5648230/
Abstract

PURPOSE

This study aimed to determine if rebamipide eyedrops can improve ocular surface damage caused by the use of glaucoma eyedrops.

METHODS

Female Kbl:Dutch rabbits were used to evaluate glaucoma eyedrop-induced ocular surface damage; one eye of each rabbit was untreated and the other was administered glaucoma eyedrops for 30 days. To evaluate the effects of rebamipide on ocular surface damage, one eye of each rabbit was administered vehicle-treated glaucoma eyedrops and the other was administered rebamipide-treated glaucoma eyedrops for 30 days. Corneal and conjunctival epithelial damage was evaluated using fluorescein and rose bengal staining, respectively. Conjunctival inflammation was observed by light microscopy with hematoxylin-eosin staining. Dark cells (in which the corneal microvilli were damaged) were analyzed by scanning electron microscopy.

RESULTS

There were no significant differences in fluorescein staining between the untreated and glaucoma eyedrop-treated groups; however, rose bengal staining and the number of inflammatory cells in the conjunctiva significantly increased after glaucoma eyedrop treatment. There was a four-fold increase in the number of dark cells in the glaucoma eyedrop-treated group compared to untreated. In contrast, in the conjunctiva of the rebamipide-treated glaucoma eyedrop group, rose bengal staining scores, the number of inflammatory cells, and the number of dark cells were decreased compared to the vehicle-treated glaucoma eyedrop group.

CONCLUSIONS

Results from our in vivo rabbit study demonstrated that short-term use of glaucoma eyedrops induces corneal epithelium disorders at the cellular level, but that simultaneous use of rebamipide has the potential to protect and repair the ocular surface.

摘要

目的

本研究旨在确定瑞巴派特滴眼液是否能改善使用青光眼滴眼液引起的眼表损伤。

方法

使用雌性Kbl:荷兰兔评估青光眼滴眼液诱导的眼表损伤;每只兔子的一只眼睛不进行处理,另一只眼睛给予青光眼滴眼液,持续30天。为了评估瑞巴派特对眼表损伤的影响,每只兔子的一只眼睛给予载体处理的青光眼滴眼液,另一只眼睛给予瑞巴派特处理的青光眼滴眼液,持续30天。分别使用荧光素和孟加拉玫瑰红染色评估角膜和结膜上皮损伤。通过苏木精-伊红染色的光学显微镜观察结膜炎症。通过扫描电子显微镜分析暗细胞(其中角膜微绒毛受损)。

结果

未处理组和青光眼滴眼液处理组之间荧光素染色无显著差异;然而,青光眼滴眼液处理后,孟加拉玫瑰红染色和结膜中的炎症细胞数量显著增加。与未处理组相比,青光眼滴眼液处理组的暗细胞数量增加了四倍。相比之下,在瑞巴派特处理的青光眼滴眼液组的结膜中,与载体处理的青光眼滴眼液组相比,孟加拉玫瑰红染色评分、炎症细胞数量和暗细胞数量均减少。

结论

我们在兔体内的研究结果表明,短期使用青光眼滴眼液会在细胞水平上诱导角膜上皮紊乱,但同时使用瑞巴派特有可能保护和修复眼表。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae5/5648230/f26567019d16/pone.0186714.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae5/5648230/e78263d5a41d/pone.0186714.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae5/5648230/0e72de5584a5/pone.0186714.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae5/5648230/f2a630c5ed83/pone.0186714.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae5/5648230/00df76ba92c2/pone.0186714.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae5/5648230/11f63e04937f/pone.0186714.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae5/5648230/f26567019d16/pone.0186714.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae5/5648230/e78263d5a41d/pone.0186714.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae5/5648230/0e72de5584a5/pone.0186714.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae5/5648230/f2a630c5ed83/pone.0186714.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae5/5648230/00df76ba92c2/pone.0186714.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae5/5648230/11f63e04937f/pone.0186714.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae5/5648230/f26567019d16/pone.0186714.g006.jpg

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本文引用的文献

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Prog Retin Eye Res. 2016 Sep;54:49-63. doi: 10.1016/j.preteyeres.2016.04.005. Epub 2016 Apr 16.
2
The Effect of Rebamipide on Ocular Surface Disorders Induced by Latanoprost and Timolol in Glaucoma Patients.瑞巴派特对青光眼患者中拉坦前列素和噻吗洛尔所致眼表疾病的影响。
J Ophthalmol. 2015;2015:689076. doi: 10.1155/2015/689076. Epub 2015 May 10.
3
The effects of 2% rebamipide ophthalmic solution on the tear functions and ocular surface of the superoxide dismutase-1 (sod1) knockout mice.
2%瑞巴派特滴眼液对超氧化物歧化酶-1(SOD1)基因敲除小鼠泪液功能和眼表的影响。
Invest Ophthalmol Vis Sci. 2013 Nov 21;54(12):7793-802. doi: 10.1167/iovs.13-13128.
4
Sodium hyaluronate decreases ocular surface toxicity induced by benzalkonium chloride-preserved latanoprost: an in vivo study.透明质酸钠降低苯扎氯铵保存的拉坦前列素引起的眼表毒性:一项体内研究。
Invest Ophthalmol Vis Sci. 2013 May 9;54(5):3385-93. doi: 10.1167/iovs.12-11181.
5
Rebamipide increases barrier function and attenuates TNFα-induced barrier disruption and cytokine expression in human corneal epithelial cells.雷贝拉唑可增加人角膜上皮细胞的屏障功能,减轻 TNFα 诱导的屏障破坏和细胞因子表达。
Br J Ophthalmol. 2013 Jul;97(7):912-6. doi: 10.1136/bjophthalmol-2012-302868. Epub 2013 Apr 20.
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A randomized, multicenter phase 3 study comparing 2% rebamipide (OPC-12759) with 0.1% sodium hyaluronate in the treatment of dry eye.一项比较 2%瑞巴派特(OPC-12759)与 0.1%玻璃酸钠治疗干眼症的随机、多中心 3 期研究。
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