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Hongshan Liu, Yong Yuan, Jianhua Zhang, Alan Jone, Winston Kao; A Dry Eye Model By Overexpression Of Interleukin-1β In Corneal Epithelium Of Krt12rtta/Tet-O-IL1b Mice. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2334.
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Dry eye is characterized by increased osmolarity of the tear and the persistent inflammation of ocular surface. However, the etiology and pathogenesis remain largely elusive. We hypothesized the overexpression of interleukinn-1β (IL1β) by corneal epithelium triggers a severe and persistent inflammation. In attempts of developing a mouse model of dry eye, we examine the ocular characteristics of tet-On Krt12-rtTA/Tet-O-IL1β bitransgenic mice that overexpress proinflammatory cytokine, IL1β, by corneal epithelium.
4 to 8 weeks old Krt12-rtTA/Tet-O-ILβ bitransgenic micewere fed doxycycline chow (Dox), and un-induced bitransgenic mice were used as control. After the different courses of induction, Dox was replaced with regular chow. Lissamine green staining was used to assess the damage of ocular surface; in vivo confocal microscopy was employed to examine the characteristics of ocular surface. The tear solution was collected for Western blot. Ocular tissues were subjected to histology, immunofluorescence staining.
One week after induction, bitransgenic mice displayed conjunctival and ciliary congestion. Two weeks later, cornea became cloudy and neovascularization, which is more easily to occur in female mice compared to male (p < 0.001). By lissamine green staining, punctuate erosions of conjunctival and corneal epithelium were detected. Confocal images revealed that cell density in the cornea was obviously increased and intensive blood vessels interspersed in cornea. Immunofluorescent staining revealed that the number of leukocytes significantly increased 72 hours, and peaked at one week after induction. Two weeks later, lymphocytes dominantly infiltrated ocular surface and the typical conjunctiva-associated lymphoid follicle proliferated in conjunctival area. The protein concentration of tear solution was significantly increased and Western blot verified that is related to the increase of cytokines. To further examine whether the inflammation can be a persistent inflammation, Dox was replaced with regular chow and the results showed it became a persistent inflammation after the continued induction for longer than 4 weeks.
The overexpression of IL1β by corneal epithelium results in a abnormal tear and persistent severe inflammation of ocular surface; the animal model of Krt12-rtTA/Tet-O-ILβ mouse mimicking dry eye can be used to study the dry eye.
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