Comparison of ocular surface mucin expression after topical ophthalmic drug administration in dry eye-induced mouse model

Inhee Moon, Hyun Goo Kang, Areum Yeo, Hyemi Noh, Hyeon Chang Kim, Jong Suk Song, Yong Woo Ji, Hyung Keun Lee

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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.

Original languageEnglish
Pages (from-to)612-620
Number of pages9
JournalJournal of Ocular Pharmacology and Therapeutics
Volume34
Issue number9
DOIs
Publication statusPublished - 2018 Nov

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All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Pharmacology
  • Pharmacology (medical)

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