Inhee Moon1, Hyun Goo Kang1, Areum Yeo1, Hyemi Noh1, Hyeon Chang Kim1,2, Jong Suk Song3, Yong Woo Ji1,4, Hyung Keun Lee1,5. 1. 1 Department of Ophthalmology, Institute of Vision Research, Yonsei University College of Medicine , Seoul, Korea. 2. 3 Department of Preventive Medicine, Yonsei University College of Medicine , Seoul, Korea. 3. 4 Department of Ophthalmology, Korea University College of Medicine , Seoul, Korea. 4. 2 Department of Ophthalmology, National Health Insurance Service Ilsan Hospital , Goyang, Korea. 5. 5 Department of Ophthalmology, Corneal Dystrophy Research Institute, Yonsei University College of Medicine , Seoul, Korea.
Abstract
PURPOSE: To determine the mucinogenic effect of dry eye (DE) treatment drugs currently in use, we compared the levels of mucin production and inflammatory cytokine expression on the ocular surfaces using a DE-induced mice model. METHODS: C57BL/6 mice were separated into 6 groups: a control group, DE-induced mice with the vehicle and treated with cyclosporine A (CsA), rebamipide (Reb), diquafosol tetrasodium (DQS), or prednisolone (Pred). The mRNA expression of MUC 1, 4, 16, 5AC, and proinflammatory cytokines on the corneal epithelia were determined by quantitative real-time polymerase chain reaction. Expression of each MUC was evaluated using flow cytometry and immunohistostaining. Conjunctival goblet cells were analyzed through periodic acid-Schiff (PAS) staining. RESULTS: Desiccating stress significantly decreased both mRNA and protein levels of all MUCs in the cornea. CsA mainly enhanced MUC5AC, with an increase in PAS-positive cells, whereas DQS chiefly increased membrane-associated mucins (MM). However, Reb only minimally increased expression of MUC5AC and Pred only increased MUC4. MUC16 did not show any significant change in any group. On the contrary, the mRNA levels of interleukin (IL)-1β, -6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were increased in the DE corneas of the control mice and were reduced by all treatments; in particular, IL-6 was significantly suppressed. CONCLUSION: Topical DQS and CsA not only ameliorated ocular surface inflammation under desiccating stress but also upregulated both MM and secretory mucins (SM) and contributed to conjunctival goblet cell recovery, compared to Reb and Pred. Both anti-inflammatory and secretory factors should be considered simultaneously when measuring the treatment effect of DE drugs.
PURPOSE: To determine the mucinogenic effect of dry eye (DE) treatment drugs currently in use, we compared the levels of mucin production and inflammatory cytokine expression on the ocular surfaces using a DE-induced mice model. METHODS: C57BL/6 mice were separated into 6 groups: a control group, DE-induced mice with the vehicle and treated with cyclosporine A (CsA), rebamipide (Reb), diquafosol tetrasodium (DQS), or prednisolone (Pred). The mRNA expression of MUC 1, 4, 16, 5AC, and proinflammatory cytokines on the corneal epithelia were determined by quantitative real-time polymerase chain reaction. Expression of each MUC was evaluated using flow cytometry and immunohistostaining. Conjunctival goblet cells were analyzed through periodic acid-Schiff (PAS) staining. RESULTS: Desiccating stress significantly decreased both mRNA and protein levels of all MUCs in the cornea. CsA mainly enhanced MUC5AC, with an increase in PAS-positive cells, whereas DQS chiefly increased membrane-associated mucins (MM). However, Reb only minimally increased expression of MUC5AC and Pred only increased MUC4. MUC16 did not show any significant change in any group. On the contrary, the mRNA levels of interleukin (IL)-1β, -6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were increased in the DE corneas of the control mice and were reduced by all treatments; in particular, IL-6 was significantly suppressed. CONCLUSION: Topical DQS and CsA not only ameliorated ocular surface inflammation under desiccating stress but also upregulated both MM and secretory mucins (SM) and contributed to conjunctival goblet cell recovery, compared to Reb and Pred. Both anti-inflammatory and secretory factors should be considered simultaneously when measuring the treatment effect of DE drugs.
Authors: Carlos Carpena-Torres; Jesus Pintor; Fernando Huete-Toral; Alba Martin-Gil; Candela Rodríguez-Pomar; Alejandro Martínez-Águila; Gonzalo Carracedo Journal: Int J Mol Sci Date: 2021-11-05 Impact factor: 5.923