Comparison of Short-Term Effects of Diquafosol and Rebamipide on Mucin 5AC Level on the Rabbit Ocular Surface

Hori, Yuichi; Kageyama, Tomofumi; Sakamoto, Asuka; Shiba, Tomoaki; Nakamura, Masatsugu; Maeno, Takatoshi

doi:10.1089/jop.2016.0092

Cited by 24 publications

(24 citation statements)

References 13 publications

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“…DQS is reported to promote not only tear secretion but also mucin secretion. 33 Because DQS increased both of these secretions might be attributable to the increase in tear stability in terms of tear quality and tear quantity, resulting in improvement of corneal epithelial damage. In this study, mucin secretion increase by DQS was not measured; however, an increase in mucin secretion could underlie the observed improvement in corneal epithelial damage.…”

Section: Discussionmentioning

confidence: 99%

<p>Effect of Diquafosol Ophthalmic Solution on Airflow-Induced Ocular Surface Disorder in Diabetic Rats</p>

Dota

Sakamoto

Nagano

et al. 2020

OPTH

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To examine the effect of 3% diquafosol ophthalmic solution (DQS) on ocular surface disorders in diabetic model rats maintained in a continuous airflow condition. Methods: Goto-Kakizaki (GK) rats, a spontaneous model of type 2 diabetes, were exposed to constant airflow for 8 weeks. After the establishment of the animal model in this environment, DQS or saline was instilled six times a day into GK rat eyes for 6 weeks. Schirmer's test was performed before and after 6-week instillations. Corneal fluorescein staining was scored at 2-, 4-, and 6-week instillations. Touch thresholds for the cornea were also determined using a Cochet-Bonnet esthesiometer before and after 6-week instillations. Results: The mean Schirmer's test score after instillation of DQS was twice higher than that recorded for saline alone. DQS significantly decreased corneal staining scores at 4-and 6-week instillations. No changes in touch thresholds were observed before and after 6-week instillations. Conclusion: These results suggest that DQS improves corneal epithelial damage by stimulating tear secretion without influencing corneal sensation in diabetic keratopathy. Thus, DQS may have potential for treatment of diabetic patients with dry eye.

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Section: Discussionmentioning

confidence: 99%

<p>Effect of Diquafosol Ophthalmic Solution on Airflow-Induced Ocular Surface Disorder in Diabetic Rats</p>

Dota

Sakamoto

Nagano

et al. 2020

OPTH

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“…71 We also compared the short-term effects on the MUC5AC level in rabbit tear fluid and conjunctival goblet cells after instilling both eyedrops. 50 Only diquafosol increased the MUC5AC level 15 minutes after one instillation. 50 These results suggested that diquafosol promotes rapid secretion of MUC5AC from conjunctival goblet cells into the tear film after instillation.…”

Section: Comparison Of Diquafosol and Rebamipidementioning

confidence: 96%

“…50 Only diquafosol increased the MUC5AC level 15 minutes after one instillation. 50 These results suggested that diquafosol promotes rapid secretion of MUC5AC from conjunctival goblet cells into the tear film after instillation. We hypothesized that diquafosol might improve tear fluid stability in the short term with its stimulatory effect on the tear fluid and mucin secretion via the P2Y2 receptor; on the other hand, rebamipide might improve the mucosal epithelia and increase the goblet cell numbers, which cure the ocular surface in patients with dry eye.…”

Section: Comparison Of Diquafosol and Rebamipidementioning

confidence: 96%

“…49 Hori et al reported that the MUC5AC level in rabbit tears increased 15 minutes after instillation of 3% diquafosol tetrasodium eyedrops. 50 In addition to MUC5AC, Takaoka-Shichijo and Nakamura reported that diquafosol increased the mRNA expression of membrane-associated mucins, MUC1, MUC4, and MUC16, after a 3-hour incubation with 100 lM diquafosol in cultured human corneal epithelial cells. 51 To date, many studies have reported the effectiveness of 3% diquafosol ophthalmic solution for treating many types of dry eye, including the aqueous deficient type, 52,53 short tear film breakup time type, [54][55][56] laser in situ keratomileusis-associated dry eye, 57,58 and obstructive meibomian gland dysfunction.…”

Section: New Therapeutic Approach For Treatment Of Dry Eyementioning

confidence: 99%

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Secreted Mucins on the Ocular Surface

Hori

2018

Invest. Ophthalmol. Vis. Sci.

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Mucins, which play important roles on the ocular surface in wettability, lubrication, and barrier function, are classified into two categories: secreted mucins and membrane-associated mucins. The most important secreted mucin on the ocular surface is MUC5AC, which is secreted by the conjunctival goblet cells. In the human conjunctiva, goblet cells are present in higher concentrations in the fornix, inferior nasal bulbar, and the lid wiper on the lid margin. The number of conjunctival goblet cells and MUC5AC expression/secretion are decreased in a patient with dry eye. In Japan, drugs that stimulate mucin secretion or increase the number of conjunctival goblet cells are commercially available. A P2Y 2 receptor, diquafosol, stimulates tear fluid secretion from conjunctival epithelial cells and promotes mucin secretion from conjunctival goblet cells. Rebamipide was marketed originally as an oral therapeutic drug to treat gastritis in Japan. Topical rebamipide increases numbers of goblet cells in the bulbar conjunctiva and the lid wiper area of palpebral conjunctiva. Many researchers have reported decreases in the ocular surface mucin expression including MUC5AC secreted by goblet cells in patients with dry eye. However, it is unknown whether changes in mucin expression on the ocular surface cause or result from dry eye. Further study is needed to determine the true mechanism of dry eye disease.

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“…6,7 In addition, diquafosol sodium increases tear volume and stimulates mucin secretion by secretary goblet cells, 7,8 as previously observed in animal models. [9][10][11][12][13] However, diquafosol does not directly act on the lacrimal glands or stimulate protein secretion. 14 Moreover, diquafosol upregulates the expression of membrane-binding mucin genes in corneal epithelial cells.…”

Section: Diquafosolmentioning

confidence: 99%

Medical Treatment for Dry Eye in Japan

Watanabe

2018

Invest. Ophthalmol. Vis. Sci.

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The etiology of dry eye has not been clarified. In the United States, the inflammation theory is supported as the main cause of dry eye, whereas the Asia Dry Eye Society has identified tear instability as the main cause. Based on this tear instability concept, the P2Y2 antagonist Diquas and the mucin secretagogue Mucosta were developed and launched in Japan over the last 5 years, and they have been widely prescribed to patients with dry eye. Moreover, Diquas has also been launched in other Asian countries, such as Korea, Thailand, and Vietnam. This report summarizes the efficacy and characteristics of these two eye drops to improve our understanding of dry eye.

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Comparison of Short-Term Effects of Diquafosol and Rebamipide on Mucin 5AC Level on the Rabbit Ocular Surface

Abstract: These data indicated that more PAS-positive MUC5AC was released into the tear fluid from the goblet cells by diquafosol than by rebamipide. There is a difference in the induction pattern of MUC5AC into the tears from the goblet cells between these eye drops.

Cited by 24 publications

References 13 publications

<p>Effect of Diquafosol Ophthalmic Solution on Airflow-Induced Ocular Surface Disorder in Diabetic Rats</p>

<p>Effect of Diquafosol Ophthalmic Solution on Airflow-Induced Ocular Surface Disorder in Diabetic Rats</p>

Secreted Mucins on the Ocular Surface

Medical Treatment for Dry Eye in Japan

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