Bin-wu Lin1, Mei-zhu Chen2, Shu-xian Fan1, Roy S Chuck3, Shi-you Zhou1. 1. The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center of Sun Yat-sen University, Guangzhou, China. 2. The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center of Sun Yat-sen University, Guangzhou, China Department of Ophthalmology, Fuzhou Dongfang Hospital, Xiamen University, Fuzhou City, Fujian Province, China. 3. The Department of Ophthalmology and Visual Science, Montefiore Medical Center, Albert Einstein College of Medicine, Yeshiva University, Bronx, New York, United States.
Abstract
PURPOSES: To investigate the effect of FK-506 eye drops on Botulinum toxin B (BTX-B)-induced mouse dry eye. METHODS: Forty-five CBA/J mice were followed up for 4 weeks after treatment with 0.025% FK-506, vehicle or 0.9% saline eye drops 3 days after intralacrimal glands injection with 20 milliunits BTX-B. Tear production, corneal fluorescein staining, the mRNA, and protein expression of cytokines were measured. The activation of nuclear factor-κB (NF-κB) was detected by Western blotting. The infiltration of inflammatory cells was examined by immunohistochemistry. RESULTS: After treated with FK-506 eye drops, aqueous tear production in the mice began to recover at week 1, and then increased to the levels of pre-BTX-B injection at week 4 (2.21 ± 0.43 vs. 2.52 ± 0.71 mm, t = 0.84, P > 0.05). The severity of corneal epithelial defects was alleviated at week 2 and further improved at week 4 when compared with those in the vehicle- and saline-treated groups. The gene expression of IL-1β and TNF-α in the FK-506 and vehicle-treated groups were 47.01% and 45.56%, 85.91% and 115.83% of that in the saline-treated group in the ocular surface, while in the lacrimal glands 49.16% and 67.60%, 94.91% and 95.77% of that in the saline-treated group, respectively. The ratio of phosphorylated IκB-α to total IκB-α in the keratoconjunctival tissues was lower in the FK-506-treated group than in the vehicle- and saline-treated groups (both P < 0.05). No inflammatory cells were detected in all groups. CONCLUSIONS: Topical application of FK-506 can inhibit NF-κB activation and related inflammatory response and alleviate the signs of dry eye. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
PURPOSES: To investigate the effect of FK-506 eye drops on Botulinum toxin B (BTX-B)-induced mousedry eye. METHODS: Forty-five CBA/J mice were followed up for 4 weeks after treatment with 0.025% FK-506, vehicle or 0.9% saline eye drops 3 days after intralacrimal glands injection with 20 milliunits BTX-B. Tear production, corneal fluorescein staining, the mRNA, and protein expression of cytokines were measured. The activation of nuclear factor-κB (NF-κB) was detected by Western blotting. The infiltration of inflammatory cells was examined by immunohistochemistry. RESULTS: After treated with FK-506 eye drops, aqueous tear production in the mice began to recover at week 1, and then increased to the levels of pre-BTX-B injection at week 4 (2.21 ± 0.43 vs. 2.52 ± 0.71 mm, t = 0.84, P > 0.05). The severity of corneal epithelial defects was alleviated at week 2 and further improved at week 4 when compared with those in the vehicle- and saline-treated groups. The gene expression of IL-1β and TNF-α in the FK-506 and vehicle-treated groups were 47.01% and 45.56%, 85.91% and 115.83% of that in the saline-treated group in the ocular surface, while in the lacrimal glands 49.16% and 67.60%, 94.91% and 95.77% of that in the saline-treated group, respectively. The ratio of phosphorylated IκB-α to total IκB-α in the keratoconjunctival tissues was lower in the FK-506-treated group than in the vehicle- and saline-treated groups (both P < 0.05). No inflammatory cells were detected in all groups. CONCLUSIONS: Topical application of FK-506 can inhibit NF-κB activation and related inflammatory response and alleviate the signs of dry eye. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
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