Diquafosol Ophthalmic Solution for Dry Eye Treatment

Nakamura, Masatsugu; Imanaka, Tadayuki; Sakamoto, Asuka

doi:10.1007/s12325-012-0033-9

Cited by 84 publications

(60 citation statements)

References 12 publications

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“…Besides inflammatory conditions, there is also an interest in the therapeutic potential of purinergic compounds in a wide range of other pathologies [228] including atherosclerotic vascular diseases [229], cancer [230,231], ocular problems [232], lower urinary tract dysfunction [233], and neurodegenerative disorders including amyotropic lateral sclerosis, multiple sclerosis and Alzheimer's disease [225]. To date only two P2 receptor antagonist are marketed: the irreversible P2Y 12 receptor antagonist clopidogrel (Plavix®), which is used as an antithrombotic agent in patients with atherosclerotic vascular disease [234] and another orally active but reversible antagonist of P2Y 12 , Ticagrelor (Brilinta®), which showed to even have a greater efficacy in reducing cardiovascular death compared with clopidogrel [235].…”

Section: Therapeutic Potential Of P2 Receptor Targetingmentioning

confidence: 99%

Purinergic signaling in inflammatory cells: P2 receptor expression, functional effects, and modulation of inflammatory responses

Jacob

Novo

Bachert

et al. 2013

Purinergic Signalling

198

158

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Extracellular ATP and related nucleotides promote a wide range of pathophysiological responses via activation of cell surface purinergic P2 receptors. Almost every cell type expresses P2 receptors and/or exhibit regulated release of ATP. In this review, we focus on the purinergic receptor distribution in inflammatory cells and their implication in diverse immune responses by providing an overview of the current knowledge in the literature related to purinergic signaling in neutrophils, macrophages, dendritic cells, lymphocytes, eosinophils, and mast cells. The pathophysiological role of purinergic signaling in these cells include among others calcium mobilization, actin polymerization, chemotaxis, release of mediators, cell maturation, cytotoxicity, and cell death. We finally discuss the therapeutic potential of P2 receptor subtype selective drugs in inflammatory conditions.

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Section: Therapeutic Potential Of P2 Receptor Targetingmentioning

confidence: 99%

Purinergic signaling in inflammatory cells: P2 receptor expression, functional effects, and modulation of inflammatory responses

Jacob

Novo

Bachert

et al. 2013

Purinergic Signalling

198

158

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“…43 The possible mechanism of that action is that DQS ophthalmic solution increases tear-film stability, thus eliminating the vicious cycle (the core mechanism of dry eye on the ocular surface) by increasing fluid secretion, mucin secretion, and membrane-binding mucin gene expression. 13 On the ocular surface of healthy subjects evaluated by meniscometry, an AT reportedly increased fluid volume for~2 min after instillation, and sodium hyaluronate increased the fluid volume for 5 min. 18 The fluid volume at 15 min after instillation of DQS was increased in the SS patients with dry eye and decreased lacrimal gland function.…”

Section: Discussionmentioning

confidence: 99%

“…11 Reportedly, DQS increases tear-film stability on the ocular surface, thereby improving the subjective symptoms and objective signs of dry eye. [12][13][14][15] In addition, DQS exhibits P2Y 2 receptor agonist activity and accelerates fluid transport from the serosal to mucosal (tear) side via chloride channel activation following intracellular calcium ion concentration elevation in the conjunctival epithelium. 16,17 The findings of a previous study suggested that the stimulatory action of DQS on fluid secretion is independent of lacrimal gland function, because the Schirmer test results for a rat model of lacrimal gland removal showed aqueous fluid secretion.…”

Section: Introductionmentioning

confidence: 99%

The increase of aqueous tear volume by diquafosol sodium in dry-eye patients with Sjögren’s syndrome: a pilot study

Yokoi

Katô

Kinoshita

2016

Eye

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Purpose To investigate the effect of 3% diquafosol sodium ophthalmic solution (DQS) on aqueous tear volume increase in dry-eye patients with Sjögren's syndrome (SS). Methods In this pilot study, 17 dry-eye patients with SS (1 male and 16 females; mean age: 66.4 years) were enrolled and underwent topical instillation of two ophthalmic solutions, artificial tears (AT) in one eye and DQS in the fellow eye, in a masked manner. The central lower tear meniscus radius (TMR) curvature was measured before and at 15 min after instillation by video-meniscometry. Simultaneously, all patients self-evaluated their symptoms of wetness and stinging using a visual analog scale (VAS, in millimeters). Results Topical instillation of DQS significantly increased the TMR at 15 min (mean: 0.21 ± 0.08 (SD) mm) compared with at baseline (mean: 0.16 ± 0.07 mm) (Po0.001, paired t-test), whereas AT had no effect at baseline (mean: 0.18 ± 0.09 mm) or at 15 min (mean: 0.18 ± 0.09 mm). The visual VAS score of wetness at 15-min post-instillation increased in both groups compared with at baseline. In the DQS-treated eyes, the postinstillation change in TMR from baseline was not correlated with the baseline value of the Schirmer test, corneal staining score, or conjunctival staining score. Conclusions Topical instillation of DQS increased aqueous tear volume on the ocular surface of dry-eye patients with SS, with its action being independent of lacrimal gland function.

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“…First studies in animal models showed its properties to enhance tear secretion (Fujihara et al, 2001;Murakami et al, 2000Murakami et al, , 2002Yerxa et al, 2002a). These results, as a secretagogue, were the prelude of Diquafosol, an ophthalmic formulation based on this compound, developed as a new treatment for dry eye and was recently approved for marketing in Japan and South Korea (Jacobson et al, 2012;Nakamura et al, 2012).…”

Section: Effect On Tear Secretionmentioning

confidence: 99%

“…Diquafosol has shown its capability to increase the aqueous and mucin portion of tears Nakamura et al, 2012;Takamura et al, 2012;Tauber et al, 2004). In recent years, diquafosol has been used for treating different conditions related with dry eye (Table 2).…”

Section: Effect On Tear Secretionmentioning

confidence: 99%

The role of dinucleoside polyphosphates on the ocular surface and other eye structures

Carracedo

Crooke

Guzmán-Aránguez

et al. 2016

Progress in Retinal and Eye Research

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a b s t r a c tDinucleoside polyphosphates comprises a group of dinucleotides formed by two nucleosides linked by a variable number of phosphates, abbreviated NpnN (where n represents the number of phosphates). These compounds are naturally occurring substances present in tears, aqueous humour and in the retina. As the consequence of their presence, these dinucleotides contribute to many ocular physiological processes. On the ocular surface, dinucleoside polyphosphates can stimulate tear secretion, mucin release from goblet cells and they help epithelial wound healing by accelerating cell migration rate. These dinucleotides can also stimulate the presence of proteins known to protect the ocular surface against microorganisms, such as lysozyme and lactoferrin. One of the latest discoveries is the ability of some dinucleotides to facilitate the paracellular way on the cornea, therefore allowing the delivery of compounds, such as antiglaucomatous ones, more easily within the eye. The compound Ap 4 A has been described being abnormally elevated in patient's tears suffering of dry eye, Sjogren syndrome, congenital aniridia, or after refractive surgery, suggesting this molecule as biomarker for dry eye condition. At the intraocular level, some diadenosine polyphosphates are abnormally elevated in glaucoma patients, and this can be related to the stimulation of a P2Y 2 receptor that increases the chloride efflux and water movement in the ciliary epithelium. In the retina, the dinucleotide dCp 4 U, has been proven to be useful to help in the recovery of retinal detachments. Altogether, dinucleoside polyphosphates are a group of compounds which present relevant physiological actions but which also can perform promising therapeutic benefits.

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Diquafosol Ophthalmic Solution for Dry Eye Treatment

Cited by 84 publications

References 12 publications

Purinergic signaling in inflammatory cells: P2 receptor expression, functional effects, and modulation of inflammatory responses

Purinergic signaling in inflammatory cells: P2 receptor expression, functional effects, and modulation of inflammatory responses

The increase of aqueous tear volume by diquafosol sodium in dry-eye patients with Sjögren’s syndrome: a pilot study

The role of dinucleoside polyphosphates on the ocular surface and other eye structures

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