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Alexis Galeno Matos, Jhimmy Talbot, Raphael Peres, Larissa Domenegueti Ferreira, Jose Carlos Alves Filho, Jayter Silva Paula; Latanoprost eye drops increases interleukine-33 in mice eyes. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3483.
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Long-term use of topical antiglaucoma drugs is associated with ocular surface inflammation and is a risk factor for trabeculectomy failure. Interleukine-33 (IL-33) is a member of the IL-1 family of cytokines and has been associated with the perpetuation of pro-inflammatory processes.
Latanoprost (0.05 mg/ml, 4 μl; N=12) or phosphate buffered saline (PBS, 4 μl, N=12) eye drops were applied to the right eye of C57BL/6 mice once a day for 10 days. After euthanasia, samples of cornea and conjunctiva were collected, at 5th and 10th day, for ELISA for IL-6 and IL-33. IL-33, IL-6 and TNF-alpha were also measured with ELISA in samples from mice 3T3 fibroblasts cultured in DMEM. These cells were treated, after reaching 80% confluence at third passage, with HBSS-Hanks added or not to latanoprost 0.05 mg/ml, for 60 min and were analyzed after 24 hours. Data were presented as mean±SEM and compared using the Student t test.
In vivo treatment with latanoprost increased IL-6 levels (91.3±4.9 pg/mg vs 140.9±14.7 pg/mg; p=0.0123) and decreased IL-33 levels (159.4 ±4.1 pg/mg vs 102.7 ± 17.9 pg/mg; p= 0.004) at 5th day. However, at 10th day, both IL-33 and IL-6 levels were increased, but not significantly. 3T3 fibroblasts treated with latanoprost showed significant higher levels of IL-33 (0.03 ±0.01 pg/mg vs 0.67 ±0.36 pg/mg; p=0.019) and TNF-alpha (0.03 ±0.01 pg/mg vs 1.66 ±0.46; p=0.024) than controls. No significant difference was observed in the comparison of IL-6 levels in vitro.
The present findings confirmed the expression of pro-inflammatory mediators in the ocular surface due to the prostaglandin analog exposure and demonstrated for the first time the increased expression of IL-33 with latanoprost treatment. Although IL-33-producing fibroblasts might play a central role in the cicatrization process, the exact effects of IL-33 on the conjunctival healing process and the initial decrease in IL-33 levels deserve further explanation.
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