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Fei Dong, Yujin Zhang, Jianhua Zhang, Chia-Yang Liu, Winston W Y Kao; Role of IL-1β in Dry Eye Diseases. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© ARVO (1962-2015); The Authors (2016-present)
Interleukin-1β (IL-1β), a pro-inflammatory cytokine, mediates the pathogenesis of dry eye diseases. We aimed to establish an inflammatory dry eye disease model via the overexpression of IL-1β by conjunctival epithelial cells for studying pathogenesis of the diseases at molecular and cellular levels.
Bitransgenic Krt4R/tetO-IL-1β mice were obtained by cross breeding transgenic tetO-IL-1β mice and Krt4-rtTA (Krt4R) driver mice (generated via knock-in strategy of IRES-rtTA transgene into the mouse Krt4 allele by CRISPR/Cas9 genome editing technique). Four weeks-old bitransgenic mice were induced to over express IL-1β in conjunctival epithelium by feeding doxycycline chow to the experimental mice for various periods of times. Stereomicroscopy, fluorescein staining, in vivo confocal HRTII microscopy, histology and immunohistochemistry staining were applied to evaluate ocular surface conditions after dox induction. Single transgenic Krt4R, tetO-IL-1β and un-induced bitransgenic Krt4R/tetO-IL-1β mice were used as controls.
Presence of inflammatory cells and corneal haze were observed in the corneas of bitransgenic IL-1βCJtg mice by in vivo HRT II confocal microscopy in three days and 2 weeks of doxycycline induction, respectively. Corneal epithelium damage was confirmed by fluorescein staining. Immunofluorescence staining of α-smooth muscle actin revealed the formation of corneal scar tissues. Histology examination showed conjunctival epithelium cornification, abnormal goblet cells, and anomaly of Meibomian glands. In contrast, the control mice did not exhibit any dry eye syndrome.
Overexpression of IL-1β by conjunctival epithelium results in ocular surface inflammation; the animal model of IL-1βCJtg mice manifesting syndrome of dry eye diseases is useful for studying the pathogenesis of dry eye diseases.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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