Antifungal efficacy of corneal collagen cross-linking on treating experimentally induced fungal keratitis of mice

Authors: Zhu Ziqian,  Qiu Shuanghao,  Yue Juan,  Liu Susu,  Gu Lizhe,  Zhang Hongmin,  Li Zhijie,  Wang Liya

DOI: 10.3760/cma.j.issn.2095-0160.2018.05.005
Published 2018-05-10
Cite as Chin J Exp Ophthalmol, 2018,36(5): 344-350.

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Objective

This study was to assess the efficacy of corneal collagen cross-linking treatment on fungal keratitis.

Methods

Eighty SPF male C57BL/6 mice aged 6-8 weeks were selected for the experiment. Fusarium solani infected model was established on the left eyes of all 80 mice.Forty mice were distributed randomly into sham operation group, model control group, scraped epithelium group and corneal collagen cross-linking (CXL) group (treated with epithelium scraped and CXL). Three days after modeling, the levels of the corneal disease severity were scored by slit lamp microscopy.The fungal activity was confirmed by plate counts.The left 40 mice were divided randomly into sham operation group, model control group, scraped epithelium group and CXL group (treated with epithelium scraped and CXL). In 1 day and 2, 3, 4, 5, 6, 7, 14 days after modeling, the corneas were examined under the slit lamp microscope.The corneal pathological examination of each group were conducted with hematoxylin and eosin staining at postoperative 14 days.The animal feeding and use was in accordance with the standards set by the ARVO, and the experiment was approved by the Ethic Committee for Experimental Animal of Henan Eye Institute.

Results

The colony-forming units (CFUs) of fungal solutions in culture significantly decreased with CXL treatment (F=11.97, P=0.00). The Pearson correlation analysis of CFU and clinical scores in CXL group showed that inflammatory cells infiltration was positively correlated with corneal disease severity (r=0.723, P=0.043). Corneal inflammatory score was significantly lower in the CXL group in various time points, with a significant differences among the groups and time points (Fgroup=34.44, P=0.00; Ftime=17.49, P=0.00). Corneal lesion and the depth of ulceration in scraped epithelium group and CXL group were remarkably lower than that in the model control group (all at P<0.05). Histopathology revealed that the degree of corneal collagen fibers destruction and the ratio of inflammatory cells infiltration in scraped epithelium group (59.33%) and CXL group (11.29%) were much lower than that in the model control group (73.65%).

Conclusions

CXL can inhibit the fungal activity effectively in the cornea of mice, and reduce the fungal induced keratitis reaction.

Key words:

Antifungal therapeutic use; Corneal collagen cross-linking; Fungal keratitis; Mice

Contributor Information

Zhu Ziqian
Henan Eye Institute, Henan Eye Hospital, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou 450003, China
Qiu Shuanghao
Henan Eye Institute, Henan Eye Hospital, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou 450003, China
Yue Juan
Henan Eye Institute, Henan Eye Hospital, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou 450003, China
Liu Susu
Henan Eye Institute, Henan Eye Hospital, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou 450003, China
Gu Lizhe
Jinzhou Medical University, Jinzhou 121001, China
Zhang Hongmin
Henan Eye Institute, Henan Eye Hospital, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou 450003, China
Li Zhijie
Key Laboratory of Regenerative Medicine, Ministry of Education, Jinan University, Institute of Ophthalmology, Guangzhou 510632, China
Wang Liya
Henan Eye Institute, Henan Eye Hospital, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou 450003, China
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