Nobuhito Tabuchi1, Hiroshi Toshida2, Daisuke Koike1, Akito Odaka3, Chikako Suto4, Toshihiko Ohta2, Akira Murakami5. 1. 1 Pharmaceutical Research Laboratories No.1, Research and Development Headquarters , Lion Corporation, Kanagawa, Japan . 2. 2 Department of Ophthalmology, Juntendo University Shizuoka Hospital , Shizuoka, Japan . 3. 3 Human and Environmental Safety Evaluation Center, Research and Development Headquarters , Lion Corporation, Kanagawa, Japan . 4. 4 Department of Ophthalmology, Tokyo Women's Medical University Medical Center East , Tokyo, Japan . 5. 5 Department of Ophthalmology, Juntendo University School of Medicine , Tokyo, Japan .
Abstract
PURPOSE: We examined the wound-healing effect of retinol palmitate (VApal) on mucin gene and protein expressions in a rat dry eye model based on lacrimal gland (LG) resection after injury. METHODS: The rat dry eye model was prepared by surgical resection of the main LG in male Long-Evans rats. After alkaline injury of the central part of the lower palpebral conjunctiva bilaterally, VApal eye drops at 1,500 IU/mL in one eye and a vehicle in the fellow eye were both administered 6 times a day for 7 days. The expression of mucin gene and protein was analyzed by real-time polymerase chain reaction or enzyme-linked immunosorbent assay in the cornea and conjunctiva of MUC1, MUC4, MUC16, and MUC5AC after 1, 3, (5), and 7 days of treatment with VApal. RESULTS: Significant decreases in fluorescein-stained areas and rose bengal scores were observed in VApal-treated dry eyes compared with vehicle-treated dry eyes at both 3 (P < 0.05) and 7 days (P < 0.01). Significant increases in corneal rMuc4 and conjunctival rMuc5AC after 1 day (P < 0.01) and conjunctival rMuc16 gene expression after 3 days were observed with VApal treatment (P < 0.05). Furthermore, conjunctival MUC16 expression significantly increased after 3 days of VApal treatment (P < 0.05). CONCLUSIONS: VApal promoted corneal rMuc4, conjunctival rMuc5AC, and conjunctival rMuc16 gene expression in a rat dry eye model after injury. VApal also promoted conjunctival MUC16 expression. These results indicate that VApal has efficacy in improving keratoconjunctival epithelial damage associated with decreased tear production.
PURPOSE: We examined the wound-healing effect of retinol palmitate (VApal) on mucin gene and protein expressions in a rat dry eye model based on lacrimal gland (LG) resection after injury. METHODS: The rat dry eye model was prepared by surgical resection of the main LG in male Long-Evans rats. After alkaline injury of the central part of the lower palpebral conjunctiva bilaterally, VApal eye drops at 1,500 IU/mL in one eye and a vehicle in the fellow eye were both administered 6 times a day for 7 days. The expression of mucin gene and protein was analyzed by real-time polymerase chain reaction or enzyme-linked immunosorbent assay in the cornea and conjunctiva of MUC1, MUC4, MUC16, and MUC5AC after 1, 3, (5), and 7 days of treatment with VApal. RESULTS: Significant decreases in fluorescein-stained areas and rose bengal scores were observed in VApal-treated dry eyes compared with vehicle-treated dry eyes at both 3 (P < 0.05) and 7 days (P < 0.01). Significant increases in corneal rMuc4 and conjunctival rMuc5AC after 1 day (P < 0.01) and conjunctival rMuc16 gene expression after 3 days were observed with VApal treatment (P < 0.05). Furthermore, conjunctival MUC16 expression significantly increased after 3 days of VApal treatment (P < 0.05). CONCLUSIONS: VApal promoted corneal rMuc4, conjunctival rMuc5AC, and conjunctival rMuc16 gene expression in a rat dry eye model after injury. VApal also promoted conjunctival MUC16 expression. These results indicate that VApal has efficacy in improving keratoconjunctival epithelial damage associated with decreased tear production.