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Young Jeung Park, Yeoun-Hee Kim, Se-Hyung Lee, Jae-Chang Jung, Cheil Eye Research Group; In Vivo Effects of Preservative-free and Preserved Prostaglandin Analogs on C57BL/6 mouse. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1475.
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To evaluate the effects of PGs with benzalkoniumchloride (BAC), alternative preservatives, or preservatives free(PF) on ocular surface C57BL/6 mouse.
C57BL/6 mice were treated with topical administration of normal saline or 5μl of several PGs once a day at 9 : 00 pm for one month. Right eyes were exposed to the following drugs: BAC 0.02%, bimatoprost 0.01% (with BAC 0.02%), latanoprost 0.005% (with BAC0.02%), tafluprost 0.0015% (with 0.001% BAC/without preservatives) and travoprost 0.004% (with 0.001% Polyquad). Corneal fluorescein staining was evaluated in all groups before harvest. Tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), human leukocyte antigen (HLA)-DR, and phospho-c-Jun N-terminalkinases(pJNK) in paraffin embedment and sectioned corneal tissues were evaluated by H&E staining and immunohistochemistry.
BAC or BAC-containing PGs showed significantly increased corneal fluorescein staining compared with normal saline, PF-PG and alternatively preserved PG treated cornea. In the H&E staining, epithelium in the tissue of normal saline, PF-PG and alternatively preserved PG treatment normally consisted of 5-6 layers of cells. Whereas, BAC or BAC-containing PGs, especially bimatoprost 0.01% (with BAC 0.02%), latanoprost 0.005% (with BAC 0.02%), treated epithelia showed irregular patterns of cell arrangement and some appeared broken. Expression levels of TNF-alpha, IL-6, HLA-DR from BAC or BAC-containing PGs treated corneal tissues increased significantly compared with that of normal saline, PF-PG and alternatively preserved PG treated mice. JNK activation by TNF-alpha and various environmental stresses implies that JNK may regulate gene expression or other biochemical function in cells also highly increased in BAC or BAC containing PGs treatment condition except in the cases of PF-PG and alternatively preserved PG treatment condition.
This in vivo study revealed that BAC-induced ocular surface toxicity is significant, although it is important to emphasize that the clinical significance of ocular surface toxicity differences observed among the different PGs formulations has not yet been firmly established. Alternatively preserved or preservative-free glaucoma medications seem to be a reasonable and viable option in selection of glaucoma medication alternative to those preserved with BAC.
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