Therapeutic efficacy of fibroblast growth factor 10 in a rabbit model of dry eye
Therapeutic efficacy of fibroblast growth factor 10 in a rabbit model of dry eye
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DOI：
10.3892/mmr.2015.4368
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发表时间：
2015-11-01
影响因子：
3.4
通讯作者：
Ke, Bilian
中科院分区：
文献类型：
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作者：
Zheng, Wenjing;Ma, Mingming;Ke, Bilian
本研究的目的是研究成纤维细胞生长因子10（FGF 10）在促进兔干眼模型中角膜上皮细胞的愈合、存活和粘蛋白表达方面的治疗功效。健康雌性新西兰白色兔12只，随机分为3组。泪腺注射单独的盐水（正常对照组）或伴刀豆球蛋白A（Con A）、局部磷酸盐缓冲盐水（PBS; PBS对照组）或25 μ g/ml FGF 10（FGF 10治疗组）。随后评估泪腺炎症、泪液功能、角膜上皮细胞完整性、细胞凋亡和粘蛋白表达。结合组织学和电子显微镜观察进行泪腺组织活检。采用傅立叶域光学相干断层扫描技术测量泪液弯月面高度（TMH）和泪液弯月面面积（TMA）。同时评估泪膜破裂时间（TBUT），并进行角膜荧光素染色。采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法计数角膜和结膜（Cj）上皮细胞（EC）凋亡的百分比。Muc 1的mRNA表达水平采用逆转录-定量聚合酶链反应分析。注射ConA后第3天，PBS组和治疗组的TMH和TMA值与正常对照组相比显著降低。然而，与PBS组相比，FGF 10治疗组的TMH和TMA分别在治疗后3天和7天更高。治疗7 d后，FGF 10治疗组角膜上皮细胞超微结构修复，角膜荧光素染色减少，TBUT延长。与PBS组相比，FGF 10治疗组中凋亡的角膜和Cj-EC的百分比显著降低。与正常对照组相比，FGF 10可显著诱导角膜上皮细胞Muc 1 mRNA的表达;与PBS对照组相比，FGF 10可诱导Cj-ECs Muc 1 mRNA的表达水平升高。本研究采用兔泪腺注射ConA 3天后成功建立兔干眼症模型。FGF 10滴眼液增加TMH和TMA，促进角膜上皮愈合，减少角膜和Cj-EC的凋亡，并导致Muc 1表达增加。
The aim of the present study was to investigate the therapeutic efficacy of fibroblast growth factor 10 (FGF10) in the promotion of healing, survival and expression of mucin in corneal epithelial cells in a rabbit dry eye model. A total of 12 healthy female New Zealand white rabbits were divided randomly into three groups. The lacrimal glands were injected with saline either alone (normal control group) or with concanavalin A (Con A), with either topical phosphate-buffered saline (PBS; PBS control group) or 25 mu g/ml FGF10 (FGF10 treatment group). Lacrimal gland inflammation, tear function, corneal epithelial cell integrity, cell apoptosis and mucin expression were subsequently assessed. Lacrimal gland tissue biopsies were performed in conjunction with histology and electron microscopy observations. Tear meniscus height (TMH) and tear meniscus area (TMA) were measured using Fourier domain-optical coherence tomography. Tear membrane break-up time (TBUT) was also assessed and corneal fluorescein staining was performed. The percentages of apoptotic corneal and conjunctival (Cj) epithelial cells (ECs) were counted using a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method. The mRNA expression levels of Muc1 were determined using reverse transcription-quantitative polymerase chain reaction analyses. The TMH and TMA values of the PBS and treatment groups were found to be significantly reduced, compared with those of the normal control group 3 days after Con A injection. However, the TMH and TMA of the FGF10 treatment group were higher, compared with those of the PBS group 3 and 7 days after treatment, respectively. Furthermore, the FGF10 treatment group exhibited prolonged TBUT, reduced corneal fluorescein staining and repaired epithelial cell ultra-structure7 days after treatment. The percentages of apoptotic corneal- and Cj-ECs in the FGF10 treatment group were significantly reduced, compared with those in the PBS group. FGF10 significantly induced the mRNA expression of Muc1 in the corneal epithelial cells, compared with the normal control group, and induced higher mRNA expression levels of Muc1 in the Cj-ECs, compared with the PBS control group. In the present study, the rabbit dry eye model was successfully established 3 days after lacrimal gland Con A injection. FGF10 eye drops increased TMH and TMA, promoted corneal epithelial healing, reduced apoptosis of the corneal- and Cj-ECs and led to increased expression of Muc1.