Abstract
Introduction
There has been rapid progress in our understanding of dry eye pathogenesis, as well as the development of improved diagnostic clinical tests. Various types of dry eye treatment drugs have been developed. This review summarizes the basic and clinical research carried out in the development of diquafosol for ophthalmic use.
Results
Diquafosol is a dinucleotide, purinoreceptor P2Y2 receptor agonist. Basic pharmacological studies have shown that it acts on P2Y2 receptors at the ocular surface, to promote tear and mucin secretion via elevated intracellular Ca2+ concentrations. Diquafosol also improves tear and mucin secretion in experimental dry eye models. Based on the results of laboratory experiments, the authors conducted a series of clinical studies in patients with dry eye disease. Diquafosol was effective in the treatment of dry eye disease at an optimal dose of 3% six times a day. In comparison to commercially available 0.1% sodium hyaluronate ophthalmic solution, 3% diquafosol ophthalmic solution showed non-inferiority in improving corneal fluorescein staining scores and superiority in improving keratoconjunctival Rose Bengal staining scores.
Conclusions
Diquafosol ophthalmic solution has a novel mechanism of action that is characterized by its stimulatory effects on tear and mucin secretion. This drug has the potential to be effective in patients with tear film instability and short break-up time type of dry eye, which are essential factors in dry eye pathogenesis.
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References
Lemp MA. Report of National Eye Institute/Industry Workshop on clinical trials in dry eyes. CLAO J. 1995;21:221–232.
Shimazaki J. Dry Eye Research Group in Japan. Definition and criteria of dry eye. Ganka. 1995;37:765–770.
DEWS members. 2007 Report of the International Dry Eye Workshop (DEWS). Ocul Surf. 2007;5:65–204.
Shimazaki J. Dry Eye Research Group in Japan. Definition and diagnosis of dry eye 2006. J Eye. 2007;24:181–184.
Fahmy AM, Hardten DR. Treating ocular surface disease: new agents in development. Clin Ophthalmol. 2011;5:465–472.
Nichols KK, Yerxa B, Kellerman DJ. Diquafosol tetrasodium: A novel dry eye therapy. Expert Opin Invest Drugs. 2004;13:47–54.
Cowlen MS, Zhang VZ, Warnock L, Moyer CF, Peterson WM, Yerxa BR. Localization of ocular P2Y2 receptor gene expression by in situ hybridization. Exp Eye Res. 2003;77:77–84.
Li Y, Kuang K, Yerxa B, Wen Q, Rosskothen H, Fischbarg J. Rabbit conjunctival epithelium transports fluid, and P2Y2 receptor agonists stimulate Cl− and fluid secretion. Am J Physiol. 2001;281:C595–C602.
Jumblatt JE, Jumblatt MM. Regulation of ocular mucin secretion by P2Y2 nucleotide receptors in rabbit and human conjunctiva. Exp Eye Res. 1998;67:341–346.
Takaoka-Shichijo Y, Murakami T, Nakamura M. Stimulatory effect of diquafosol tetrasodium on tear fluid secretion in normal rabbits. J Eye. 2011;28:1029–1033.
Murakami T, Fujita H, Fujihara T, Nakamura M, Nakata K. Novel non-invasive sensitive determination of tear volume changes in cats. Ophthalmic Res. 2002;34:371–374.
Fujihara T, Murakami T, Fujita H, Nakamura M. Nakata K. Improvement of corneal barrier function by the P2Y2 agonist INS365 in a rat dry eye model. Invest Ophthalmol Vis Sci. 2001;42:96–100.
Fujihara T, Murakami T, Nagano T, Nakamura M, Nakata K. INS365 suppresses loss of corneal epithelial integrity by secretion of mucin-like glycoprotein in a rabbit short-term dry eye model. J Ocul Pharmacol Ther. 2002;18:363–370.
Murakami T, Fujihara T, Horibe Y, Nakamura M. Diquafosol elicits increases in net Cl− transport through P2Y2 receptor stimulation in rabbit conjunctiva. Ophthalmic Res. 2004;36:89–93.
Takaoka-Shichijo Y, Shinomiya K, Katsuta O, Nakamura M. Stimulatory action of diquafosol tetrasodium on mucin-like glucoprotein secretion in rabbit conjunctival tissues. J Eye. 2011;28:543–548.
Takaoka-Shichijo Y, Sakamoto A, Nakamura M. Effect of diquafosol tetrasodium on MUC5AC secretion by rabbit conjunctival tissues. J Eye. 2011;28:261–265.
Takaoka-Shichijo Y, Nakamura M. Stimulatory effect of diquafosol tetrasodium on the expression of membrane-binding mucin genes in cultured human corneal epithelial cells. J Eye. 2011;28:425–429.
Nakamura M, Imanaka T. New treatment for dry eye: diquafosol tetrasodium. Jpn J Ocular Pharmacol. 2011;25:42–46.
Matsumoto Y, Ohashi Y, Watanabe H, Tsubota K; Diquafosol Ophthalmic Solution Phase 2 Study Group. The efficacy and safety of diquafosol ophthalmic solution in patients with dry eye syndrome: a Japanese phase 2 clinical trial. Ophthalmology. 2012; Jun 25 [Epub ahead of print].
Takamura E, Tsubota K, Watanabe H, Ohashi Y. A randomized, double-masked comparison study of diquafosol versus sodium hyaluronate ophthalmic solutions in dry eye patients. Br J Ophthalmol. In press.
Yamaguchi M, Tsubota K, Watanabe H, Ohashi Y. The safety and efficacy of long-term treatment with 3% diquafosol ophthalmic solution for dry eye. J Eye. 2012;29:527–535.
Nelson JD. In-office diagnostic tests for dry eye disease. In: Asbell PA, Lemp MA, eds. Dry Eye Disease: The Clinician’s Guide to Diagnosis and Treatment. New York: Thieme Medical Publishers; 2006:33–46.
Kaido M, Matsumoto Y, Shigeno Y, Ishida R. Dogru M. Corneal fluorescein staining correlates with visual function in dry eye patients. Invest Ophthalmol Vis Sci. 2011;52:9516–9522.
Watanabe H. Significance of mucin on the ocular surface. Cornea. 2002;21:S17–S22.
Dua HS, Kruse FE. Innovations in the treatment of dry eye disease: mucin stimulators and hormone replacement. In: Asbell PA, Lemp MA, eds. Dry Eye Disease: The Clinician’s Guide to Diagnosis and Treatment. New York: Thieme Medical Publishers; 2006:108–113.
Dogru M, Tsubota K. Pharmacotherapy of dry eye. Expert Opin Pharmacother. 2011;12:325–333.
Shimazaki J. Risk factors for dry eye syndrome. Ganka. 2011;53:1553–1557.
Sakamoto A, Takaoka-Shichijo Y, Yamashita N, Nakamura M. Combined effect of diquafosol tetrasodium and purified HA ophthalmic solutions on tear fluid volume in normal rabbits. J Eye. In press.
Dota A, Nakamura M. Combined effect of diquafosol tetrasodium and HA ophthalmic solutions in rat dry eye model. J Eye. 2011;28:1477–1481.
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Nakamura, M., Imanaka, T. & Sakamoto, A. Diquafosol Ophthalmic Solution for Dry Eye Treatment. Adv Therapy 29, 579–589 (2012). https://doi.org/10.1007/s12325-012-0033-9
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DOI: https://doi.org/10.1007/s12325-012-0033-9