Therapeutic effects of topical doxycycline in a benzalkonium chloride-induced mouse dry eye model.
OBJECTIVE
We investigated the therapeutic effects and underlying mechanisms of topical doxycycline in a benzalkonium chloride (BAC)-induced mouse dry eye model.


METHODS
Eye drops containing 0.025%, 0.1% doxycycline or solvent were administered to a BAC-induced dry eye model four times daily. The clinical evaluations, including tear break-up time (BUT), fluorescein staining, inflammatory index, and tear volume, were performed on days 0, 1, 4, 7, and 10. Global specimens were collected on day 10 and processed for immunofluorescent staining, TUNEL, and periodic acid-Schiff assay. The levels of inflammatory mediators in the corneas were determined by real-time PCR. The total and phosphorylated nuclear factor-κB (NF-κB) were detected by Western blot.


RESULTS
Both 0.025% and 0.1% doxycycline treatments resulted in increased BUT, lower fluorescein staining scores, and inflammatory index on days 4, 7, and 10, while no significant change in tear volume was observed. The 0.1% doxycycline-treated group showed more improvements in decreasing fluorescein staining scores, increasing Ki-67-positive cells, and decreasing TUNEL- and keratin-10-positive cells than other groups. The mucin-filled goblet cells in conjunctivas were increased, and the expression of CD11b and levels of matrix metalloproteinase-9, IL-1β, IL-6, TNF-α, macrophage inflammatory protein-2, and cytokine-induced neutrophil chemoattractant in corneas were decreased in both doxycycline-treated groups. In addition, doxycycline significantly reduced the phosphorylation of NF-κB activated in the BAC-treated corneas.


CONCLUSIONS
Topical doxycycline showed clinical improvements and alleviated ocular surface inflammation on BAC-induced mouse dry eye, suggesting a potential as an anti-inflammatory agent in the clinical treatment of dry eye.
Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, China.
Zhen
Z
Zhang
Wen-Zhao
WZ
Yang
Zhen-Zhen
ZZ
Zhu
Qian-Qian
QQ
Hu
Yan-Feng
YF
Chen
Hui
H
He
Yong-Xiong
YX
Chen
Zu-Guo
ZG
Liu
D000287:Administration, Topical; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D001548:Benzalkonium Compounds; D049109:Cell Proliferation / Q000187:drug effects; D003315:Cornea / Q000187:drug effects; D004195:Disease Models, Animal; D004318:Doxycycline / Q000008:administration & dosage*; D015352:Dry Eye Syndromes / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D020397:Goblet Cells / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000187:drug effects
D000900:Anti-Bacterial Agents; D001548:Benzalkonium Compounds; D016328:NF-kappa B; D004318:Doxycycline
anti-inflammation; benzalkonium chloride; dry eye; topical doxycycline