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Katsuhiko Shinomiya, Mayumi Ueta, Maki Kobori, Kenji Nakanishi, Norihiko Yokoi, Shigeru Kinoshita; Usefulness of a Dry-eye Mouse Model Produced by Exorbital Lacrimal Gland Excision and Analysis of the Increase of Caspase-1 Independent IL-1 β in the Tear Fluid of Those Mice. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2335.
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For the production of a dry-eye mouse model, previously reported methods include the topical administration of benzalkonium chloride, injection of botulinum toxin into the lacrimal gland, and breeding mice in a low humidity environment combined with scopolamine administrations. The purpose of this present study was to report the usefulness of a new dry-eye mouse model produced by exorbital lacrimal gland excision. Since it has been reported that inflammatory cytokine interleukin-1 beta (IL-1 β) increases in the tear fluid of dry eye patients, we examined IL-1 β production in the tear fluid of our new dry-eye mouse model. Moreover, we examined whether caspase-1 contributed to the IL-1 β production in the tear fluid, because it has also been reported that caspase-1 is important for IL-1 β production.
Unilateral excision of the exorbital lacrimal gland was performed on caspase-1 knockout (Casp1-KO) and C57BL/6 (WT) mice. To evaluate dry eye symptoms, we performed fluorescein staining and measured tear production every two weeks after surgery, and then compared the data obtained from the untreated eyes with that obtained from the exorbital lacrimal gland excised eyes. IL-1 β production in the tear fluid of each mouse was measured by ELISA.
Tear production in the exorbital lacrimal gland excised mice (Casp1-KO and WT) was significantly decreased and superficial punctate keratitis (SPK) was observed. IL-1 β production in the tear fluid of exorbital lacrimal gland excised mice (both Casp1-KO and WT) was increased compared with untreated eyes. In addition, IL-1 β production in the tear fluid of Casp1-KO mice (both with and without surgery) was not lower than that in the WT mice.
Persistent tear-volume reduction and SPK was induced, thus indicating that the exorbital lacrimal gland excised mouse is useful as a dry eye mouse model and for the investigation of dry-eye pathogenesis. The increase of IL-1 β in tear fluid might indicate that persistent tear-volume reduction causes some kind of inflammatory reaction. Interestingly, the increases of IL-1 β in the tear fluid of our dry-eye Casp1-KO model mirrored that in the WT mice, suggesting that IL-1 β production is independent of caspase-1.
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