Skip to main content
Log in

Expression of the P2Y2 receptor on the rat ocular surface during a 1-year rearing period

Japanese Journal of Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

P2Y2 receptors are expressed on ocular surface tissues. Diquafosol ophthalmic solution (DIQUAS® ophthalmic solution 3 %; Santen Pharmaceutical Co., Ltd.) acts on these receptors and promotes the secretion of water and mucin. It has been shown to be an efficient dry eye treatment. If P2Y2 receptor expression on the ocular surface decreases with age, the effect of diquafosol may be reduced in elderly persons. In this study, we investigated the changes in P2Y2 receptor expression on the rat ocular surface over an extended period of time.

Methods

P2Y2 receptor expression in the conjunctiva, cornea, meibomian gland and lacrimal glands of male and female Sprague–Dawley rats was examined from 5 weeks until 53 weeks of age using immunostaining and quantitative-PCR.

Results

In the immunohistological examinations, P2Y2 receptor expression was observed in the conjunctival epithelium containing goblet cells, corneal epithelium, meibomian gland ductal epithelium and lacrimal gland ductal epithelium. However, its expression was not significantly different between each age group or between sexes. Regarding P2Y2 receptor mRNA expression, there was an age-related increase in the bulbar conjunctiva. In particular, a significant increase was observed in the 53-week-old age group as compared to the 5-week-old female age group. However, age-related changes in expression were not observed in the cornea or meibomian gland in males or females.

Conclusions

We observed no significant age-related decrease was observed for P2Y2 receptor protein and mRNA expression on rat ocular surface tissues.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price includes VAT (France)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

References

  1. Fries JE, Wheeler-Schilling TH, Guenther E, Kohler K. Expression of P2Y1, P2Y2, P2Y4, and P2Y6 receptor subtypes in the rat retina expression of P2Y1, P2Y2, P2Y4, and P2Y6 receptor subtypes in the rat retina. Invest Ophthalmol Vis Sci. 2004;45:3410–7.

    Article  PubMed  Google Scholar 

  2. Ralevic V, Burnstock G. Receptors for purines and pyrimidines. Pharmacol Rev. 1998;50:413–92.

    CAS  PubMed  Google Scholar 

  3. Hosoya K, Ueda H, Kim KJ, Lee VH. Nucleotide stimulation of Cl(−) secretion in the pigmented rabbit conjunctiva. J Pharmacol Exp Ther. 1999;291(1):53–9.

    CAS  PubMed  Google Scholar 

  4. Shiue MH, Kulkarni AA, Gukasyan HJ, Swisher JB, Kim KJ, Lee VH. Pharmacological modulation of fluid secretion in the pigmented rabbit conjunctiva. Life Sci. 2000;66:PL105–11.

    Article  CAS  PubMed  Google Scholar 

  5. Murakami T, Fujihara T, Nakamura M, Nakata K. P2Y(2) receptor stimulation increases tear fluid secretion in rabbits. Curr Eye Res. 2000;21:782–7.

    Article  CAS  PubMed  Google Scholar 

  6. Dartt DA. Regulation of mucin and fluid secretion by conjunctival epithelial cells. Prog Retin Eye Res. 2002;21:555–76.

    Article  CAS  PubMed  Google Scholar 

  7. Murakami T, Fujihara T, Nakamura M, Nakata K. P2Y(2) receptor elicits PAS-positive glycoprotein secretion from rabbit conjunctival goblet cells in vivo. J Ocul Pharmacol Ther. 2003;19:345–52.

    Article  CAS  PubMed  Google Scholar 

  8. Pendergast W, Yerxa BR, Douglass JG 3rd, Shaver SR, Dougherty RW, Redick CC, et al. Synthesis and P2Y receptor activity of a series of uridine dinucleoside 5′-polyphosphates. Bioorg Med Chem Lett. 2001;11:157–60.

    Article  CAS  PubMed  Google Scholar 

  9. Nakamura M, Imanaka T. New treatment for dry eye: diquafosol tetrasodium. Jpn J Ocular Pharmacol. 2011;25:42–6.

    Google Scholar 

  10. 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;119:1954–60.

    Article  PubMed  Google Scholar 

  11. Takamura E, Tsubota K, Watanabe H, Ohashi Y, Diquafosol Ophthalmic Solution Phase 3 Study Group. A randomized, double-masked comparison study of diquafosol versus sodium hyaluronate ophthalmic solutions in dry eye patients. Br J Ophthalmol. 2012;96:1310–5.

    Article  PubMed Central  PubMed  Google Scholar 

  12. 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;29:527–35.

    Google Scholar 

  13. Koh S, Ikeda C, Takai Y, Watanabe H, Maeda N, Nishida K. Long-term results of treatment with diquafosol ophthalmic solution for aqueous-deficient dry eye. Jpn J Ophthalmol. 2013;57:440–6.

    Article  CAS  PubMed  Google Scholar 

  14. Tauber J, Davitt WF, Bokosky JE, Nichols KK, Yerxa BR, Schaberg AE, et al. Double-masked, placebo-controlled safety and efficacy trial of diquafosol tetrasodium (INS365) ophthalmic solution for the treatment of dry eye. Cornea. 2004;23:784–92 (Erratum in Cornea. 2007; 264: 514).

    Article  CAS  PubMed  Google Scholar 

  15. Kamiya K, Nakanishi M, Ishii R, Kobashi H, Igarashi A, Sato N, et al. Clinical evaluation of the additive effect of diquafosol tetrasodium on sodium hyaluronate monotherapy in patients with dry eye syndrome: a prospective, randomized, multicenter study. Eye (Lond). 2012;26:1363–8.

    Article  CAS  Google Scholar 

  16. Shimazaki-Den S, Iseda H, Dogru M, Shimazaki J. Effects of diquafosol sodium eye drops on tear film stability in short BUT type of dry eye. Cornea. 2013;32:1120–5.

    Article  PubMed  Google Scholar 

  17. Arita R, Suehiro J, Haraguchi T, Maeda S, Maeda K, Tokoro H, et al. Topical diquafosol for patients with obstructive meibomian gland dysfunction. Br J Ophthalmol. 2013;97:725–9.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Johansson PA, Burnstock G, Dziegielewska KM, Guida E, McIntyre P, Saunders NR. Expression and localization of P2 nucleotide receptor subtypes during development of the lateral ventricular choroid plexus of the rat. Eur J Neurosci. 2007;25:3319–31.

    Article  CAS  PubMed  Google Scholar 

  19. Giaroni C, Knight GE, Zanetti E, Chiaravalli AM, Lecchini S, Frigo G, et al. Postnatal development of P2 receptors in the murine gastrointestinal tract. Neuropharmacology. 2006;50:690–704.

    Article  CAS  PubMed  Google Scholar 

  20. Afework M, Burnstock G. Changes in P2Y2 receptor localization on adrenaline- and noradrenaline-containing chromaffin cells in the rat adrenal gland during development and aging. Int J Dev Neurosci. 2005;23:567–73.

    Article  CAS  PubMed  Google Scholar 

  21. Miao LY, Tang JP, Esposito DP, Zhang JH. Age-related changes in P2 receptor mRNA of rat cerebral arteries. Exp Gerontol. 2001;37:67–79.

    Article  CAS  PubMed  Google Scholar 

  22. 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.

    Article  CAS  PubMed  Google Scholar 

  23. Ishibashi K, Okamura K, Yamazaki J. Involvement of apical P2Y2 receptor-regulated CFTR activity in muscarinic stimulation of Cl(−) reabsorption in rat submandibular gland. Am J Physiol Regul Integr Comp Physiol. 2008;294:R1729–36.

    Article  CAS  PubMed  Google Scholar 

  24. Coutinho-Silva R, Parsons M, Robson T, Burnstock G. Changes in expression of P2 receptors in rat and mouse pancreas during development and ageing. Cell Tissue Res. 2001;306:373–83.

    Article  CAS  PubMed  Google Scholar 

  25. Fujihara T, Murakami T, Fujita H, Nakamura M, Nakata K. Improvement of corneal barrier function by the P2Y(2) agonist INS365 in a rat dry eye model. Invest Ophthalmol Vis Sci. 2001;42:96–100.

    CAS  PubMed  Google Scholar 

  26. 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;18:363–70.

    Article  CAS  PubMed  Google Scholar 

  27. Nakamura M, Imanaka T, Sakamoto A. Diquafosol ophthalmic solution for dry eye treatment. Adv Ther. 2012;29:579–89.

    Article  CAS  PubMed  Google Scholar 

  28. Nichols KK, Yerxa B, Kellerman DJ. Diquafosol tetrasodium: a novel dry eye therapy. Expert Opin Investig Drugs. 2004;13:47–54.

    Article  CAS  PubMed  Google Scholar 

  29. Alves M, Cunha DA, Calegari VC, Saad MJ, Boschero AC, Velloso LA, et al. Nuclear factor-kappaB and advanced glycation end-products expression in lacrimal glands of aging rats. J Endocrinol. 2005;187:159–66.

    Article  CAS  PubMed  Google Scholar 

  30. Kawashima M, Kawakita T, Okada N, Ogawa Y, Murat D, Nakamura S, et al. Calorie restriction: a new therapeutic intervention for age-related dry eye disease in rats. Biochem Biophys Res Commun. 2010;397:724–8.

    Article  CAS  PubMed  Google Scholar 

Download references

Conflicts of interest

H. Tanioka, Employee (Santen Pharmaceutical Co. Ltd.); Y. Kuriki, Employee (Santen Pharmaceutical Co. Ltd.); A. Sakamoto, Employee (Santen Pharmaceutical Co. Ltd.); O. Katsuta, Employee (Santen Pharmaceutical Co. Ltd.); K. Kawazu, Employee (Santen Pharmaceutical Co. Ltd.); M. Nakamura, Employee (Santen Pharmaceutical Co. Ltd.).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hidetoshi Tanioka.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tanioka, H., Kuriki, Y., Sakamoto, A. et al. Expression of the P2Y2 receptor on the rat ocular surface during a 1-year rearing period. Jpn J Ophthalmol 58, 515–521 (2014). https://doi.org/10.1007/s10384-014-0342-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10384-014-0342-4

Keywords

Navigation