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KEISUKE ADACHI, Toshiaki Hirakata, Yosuke Asada, Satoshi Iwamoto, Susumu Nakae, Akira Matsuda; The role of interleukin-33 in retinal tissue fibrosis after laser injury. Invest. Ophthalmol. Vis. Sci. 2018;59(9):344.
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Interleukin-33 (IL-33) is an IL-1 family cytokine, known to have pro-fibrotic function as other Th2 cytokines. We previously reported that IL-33 expression was observed in the nucleus of Muller cells and recombinant IL-33 injection to the vitreous induced the expression of TGF-beta1, TIMP-1 and COL1A1 in the retinal tissue (ARVO 2014). In this study, we examined the roles of IL-33 in tissue repair after laser injury in the mouse retinal tissue using IL-33 knockout (KO) mice and congenic wild-type mice.
Laser photocoagulations (50 micrometer, 100 mW, 100 ms) were performed in unilateral eye of C57BL/6-IL-33 KO and congenic wild-type mice. Il33, Il4, Il5, Il13, Il6, and Ccl2 expression after laser injury of the retina was evaluated chronologically (24, 72, 168 hours after injury) with realtime-PCR. Expression of fibrosis-related genes (Col1a1 and Acta2) was also quantified.
Statistically significant Il33 upregulation was observed from 24 to 72 hour after laser injury in the retinal tissue in wild-type mice. Old mice (16week-old) showed higher Il33 expression (4.21 fold) than young mice (8week-old). Upregulation of Th2 cytokine (Il4, Il5, Il13) expression was observed in wild-type mice after laser injury and significant attenuation of Th2 cytokine expression (Il4; 0.2fold, Il5; 0.36fold, Il13; 0.47fold) was noted in IL-33 KO mice 24 hour after laser injury. The expression of macrophage activation-related genes (Ccl2 and Il6) was peaked at 24 hour after laser injury, and significant reduction of the expression was observed in the IL-33 KO mice (Ccl2; 0.17fold, Il6; 0.23fold) compared to the wild type mice. The expression of fibrosis related genes (Col1a1 and Acta2) was peaked at 168 hours after laser injury and significant attenuation (Col1a1; 0.4fold, Acta2; 0.33fold) of expression was noted in IL-33 KO mice.
Laser injury increased IL-33 expression in mouse retinal tissue and may promote retinal fibrotic changes through activation of Th2 type inflammation-related and macrophage activation-related signaling pathways.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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