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一种新型局部眼用制剂减轻体内急性芥子气角膜病变的初步研究

A Novel Topical Ophthalmic Formulation to Mitigate Acute Mustard Gas Keratopathy In Vivo: A Pilot Study.

作者信息

Tripathi Ratnakar, Balne Praveen K, Sinha Nishant R, Martin Lynn M, Kamil Sabeeh, Landreneau James R, Gupta Suneel, Rodier Jason T, Sinha Prashant R, Hesemann Nathan P, Hofmann Alexandria C, Fink Michael K, Chaurasia Shyam S, Mohan Rajiv R

机构信息

Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, USA.

One-Health Vision Research Program, Departments of Veterinary Medicine and Surgery and Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.

出版信息

Transl Vis Sci Technol. 2020 Nov 2;9(12):6. doi: 10.1167/tvst.9.12.6. eCollection 2020 Nov.

DOI:10.1167/tvst.9.12.6
PMID:33200047
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7645241/
Abstract

PURPOSE

This pilot study investigated the in vivo therapeutic potential and tolerability of a multimodal ophthalmic formulation, topical eye drops (TED), for acute mustard gas keratopathy (MGK) using a rabbit model.

METHODS

Twenty New Zealand White rabbits were used. Only right eyes of 18 rabbits (oculus dexter [OD]) received single sulfur mustard gas (SM) vapor injury, whereas contralateral eyes were left untreated or received TED for tolerabilty evaluation. Two rabbit eyes received no treatment and served as age-matched naive control. The four groups were: Naive (oculus sinister [OS] untreated eyes; n = 9); TED (OS treated only with TED BID for 3 days; n = 9); SM (OD exposed to SM vapor; n = 9); and SM+TED (OD exposed to SM+TED BID for 3 days; n = 9). Ocular examination in live rabbits were performed utilizing slit-lamp biomicroscopy, Fantes grading system, fluorescein staining, Schirmer's tests, pachymetry, and applanation tonometry. Cellular and molecular changes in rabbit corneas were assessed after humane euthanasia on day-3 and day-7 with histopathological and real-time polymerase chain reaction PCR techniques.

RESULTS

TED to rabbit eyes was found tolerable in vivo. SM-exposed eyes showed significant increase in Fantes scores, central corneal thickness (CCT), Schirmer's test, epithelium-stroma separation, and corneal edema. TED mitigated clinical symptoms by reducing corneal edema, Fantes scores, CCT, and Schirmer's test. Further, TED decreased SM-induced corneal haze, inflammatory and profibrotic markers, transforming growth factor-TGF-β1 and cyclooxygenase-2COX-2, and damage to corneal structure, including epithelial-stromal integrity.

CONCLUSIONS

The developed multimodal eyedrop formulation, TED, has potential to mitigate acute MGK effectively in vivo.

TRANSLATIONAL RELEVANCE

TED is effective against MGK.

摘要

目的

本初步研究使用兔模型，调查了一种多模式眼科制剂——局部滴眼液（TED）对急性芥子气角膜病变（MGK）的体内治疗潜力和耐受性。

方法

使用20只新西兰白兔。18只兔子的右眼（右眼[OD]）接受单次硫芥子气（SM）蒸气损伤，而对侧眼不进行处理或接受TED以评估耐受性。2只兔眼未接受治疗，作为年龄匹配的未处理对照。四组分别为：未处理组（左眼[OS]未处理眼；n = 9）；TED组（OS仅用TED每日两次治疗3天；n = 9）；SM组（OD暴露于SM蒸气；n = 9）；SM + TED组（OD暴露于SM并每日两次给予TED治疗3天；n = 9）。对活兔进行眼部检查，采用裂隙灯生物显微镜检查、Fantes分级系统、荧光素染色、泪液分泌试验、角膜测厚和压平眼压测量。在第3天和第7天进行人道安乐死后，用组织病理学和实时聚合酶链反应PCR技术评估兔角膜的细胞和分子变化。

结果

发现TED对兔眼在体内具有耐受性。暴露于SM的眼睛在Fantes评分、中央角膜厚度（CCT）、泪液分泌试验、上皮 - 基质分离和角膜水肿方面显著增加。TED通过减轻角膜水肿、Fantes评分、CCT和泪液分泌试验来缓解临床症状。此外，TED降低了SM诱导的角膜混浊、炎症和促纤维化标志物、转化生长因子 - TGF-β1和环氧化酶 - 2COX - 2，以及对角膜结构的损害，包括上皮 - 基质完整性。

结论

所开发的多模式滴眼液制剂TED在体内具有有效减轻急性MGK的潜力。

转化相关性

TED对MGK有效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d21/7645241/dbd7487384c0/tvst-9-12-6-f008.jpg
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