Therapeutic Effects And Mechanisms Of Basic Fibroblast Growth Factor On Benzalkonium Chloride-induced Dry Eye In A Mouse Model

Purpose To evaluate the therapeutic effects and possible mechanisms of basicFibroblast Growth Factor (bFGF) on the mouse dry eye model induced byBenzalkonium Chloride (BAC).Methods75male BALB/c mice (150eyes) were treated with topical administrationof0.2%BAC to induce dry eye. Choose the consistency of break-up time of tear film(BUT), corneal fluorescein staining scores and inflammation index, on day(D)23after the BAC treatment, the eyes were re-selected and randomly divided into A, B, C,D four groups: control(dry eye) group, vehicle-treated group, bFGF5000IU eyedrops-treated and bFGF25000IU eye drops-treated group. Clinical evaluations ofBUTs, corneal fluorescein staining, and inflammatory index were performed on days0,1,3and5. Global specimens were collected on D6and the following examinationswere performed: H&E staining, periodic acid-Schiff (PAS) assay, cornealimmunostaianing of Ki-67and cytokeratin19(K19), and corneal Western blot ofMUC-1and P63. After the treatment, removing eyeballs of mice and staining themwith HE and periodic acid Schiff (PAS), Immunohistochemical staining with Ki-67,immune fluorescent labeling with cytokeratin19(K19), then detect expression level ofMuc-1and P63of Angle of conjunctival tissue.Results80eyes were included in the sequential experiment,20eyes for each group.There were no clinical differences among the groups on day0,1and3.On day5, theBUT was (2.176±0.828),(1.941±0.464),(2.389±0.719),(2.833±0.924)s in groupA, B, C and D respectively, the BUT in group C and D were significant longer thanthose of group A and B (F=4.426, P=0.007). The statistical results of clinicalevaluations showed no significant changes in corneal fluorescein staining and inflammatory (F=0.401, P=0.753),(F=0.719, P=0.544). Corneal morphology showedthe feature of thicker corneal epithelial layer in group A and B, and uniformity intopical application of bFGF. bFGF relatively increased the number of goblet cells andthe expression of MUC1in the epithelium, but showed no significant changes ongoblet cells (F=4.481, P=0.06). Meanwhile, bFGF significantly increased Ki-67(F=73.418, P=0.000)，K19and P63positive cells and decreased K10positive cells,and the result of group D was more obvious.Conclusion bFGF presented a certain therapeutic agent on the BAC-induced mousedry eye, by the possible function of stabilizing the tear film and maintaining theintegrity of corneal epithelium.