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Effect of topical prostaglandin D2 on the aqueous humor dynamics in rabbits

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Abstract

Effects of topically applied prostaglandin (PG) D2 on the aqueous outflow facility, uveoscleral flow, and aqueous flow rate were studied in rabbits to reveal its intraocular pressure (IOP)-reducing mechanism. The outflow facility after PGD2 application (50 μg) as measured by 2-min tonography was 0.19 μl/min/mm Hg and did not differ from that before the application (0.22) or from that of the control contralateral eye (0.21). Direct measurement of the uveoscleral flow by perfusion of the anterior chamber for 30 min with fluorescein isothiocyanate-labeled dextran solution showed the flow rate to be about 0.15 μl/min in indomethacin-treated (10 mg/kg, i.p.) rabbits. In these animals, PGD2 (50 μg) was ineffective in changing the flow rate, while PGF2α (50 μg) significantly increased the flow by about 35%. Indirect assessment of the effects of PGs on this flow system was made using the uveoscleral flow-antagonizing ability of topical pilocarpine (1.5 mg). IOP reduction by PGD2 (50 μg) was only slightly inhibited by pilocarpine, while that by PGF2α (10 μg) was markedly reduced. Aqueous flow rate measured fluorophotometrically was about 3.5 μl/min in normal eyes. After PGD2 (50 μg) the flow rate was significantly reduced to 3.0 μl/min. The magnitude of this reduction was estimated to be enough to account for the IOP reduction after application of 50 μg of PGD2. These results indicate that IOP reduction caused by topical PGD2 application is due mostly to the inhibition of aqueous flow rate.

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References

  1. Becker B, Constant MA (1965) The facility of aqueous outflow. Arch Ophthalmol 55:305–312

    Google Scholar 

  2. Bill A (1966) The routes for bulk drainage of aqueous humour in rabbits with and without cyclodialysis. Doc Ophthalmol 20:157–169

    Google Scholar 

  3. Bill A (1967) Effects of atropine and pilocarpine on aqueous humour dynamics in cynomolgus monkeys (Macaca irus). Exp Eye Res 6:120–125

    Google Scholar 

  4. Bill A (1971) Aqueous humor dynamics in monkeys (Macaca irus andCercopithecus ethiops). Exp Eye Res 11:195–206

    Google Scholar 

  5. Bundy GL, Morton DR, Peterson DC, Nishizawa EE, Miller WL (1983) Synthesis and platelet aggregation inhibiting activity of prostaglandin D analogues. J Med Chem 26: 790–799

    Google Scholar 

  6. Camras CB, Bito LZ, Eakins KE (1977) Reduction of intraocular pressure by prostaglandins applied topically to the eyes of conscious rabbits. Invest Ophthalmol Vis Sci 16:1125–1134

    Google Scholar 

  7. Caprioli J, Sears M (1983) Forskolin lowers intraocular pressure in rabbits, monkeys, and man. Lancet I:958–960

    Google Scholar 

  8. Caprioli J, Sears M (1984) Combined effect of forskolin and acetazolamide on intraocular pressure and aqueous flow in rabbit eyes. Exp Eye Res 39:47–50

    Google Scholar 

  9. Coleman RA (1987) Methods in prostanoid receptor classification. In: Benedetto C, McDonald-Gibson RG, Nigam S, Slater TF (eds) Prostaglandins and related substances. IRL Press, Oxford, pp 267–303

    Google Scholar 

  10. Crawford K, Kaufman PL (1987) Pilocarpine antagonizes prostaglandin F2α-induced ocular hypotension in monkeys. Arch Ophthalmol 105:1112–1116

    Google Scholar 

  11. Goh Y, Nakajima M, Azuma I, Hayaishi O (1986) Prostaglandin D2 reduces intraocular pressure: a possible therapeutic agent for glaucoma. Proc Int Soc Eye Res 4:14

    Google Scholar 

  12. Goh Y, Nakajima M, Azuma I, Hayaishi O (1986) The correlation between ocular hypotensive and anterior uveal adenylate cyclase-stimulating activities of PGD2-related compounds. Acta Soc Ophthalmol Jpn 91 [Suppl]:181

    Google Scholar 

  13. Goh Y, Nakajima M, Azuma I, Hayaishi O (1988) Prostaglandin D2 reduces intraocular pressure. Br J Ophthalmol 72:461–464

    Google Scholar 

  14. Goh Y, Nakajima M, Azuma I, Hayaishi O (1989) Effects of prostaglandin D2 and its analogues on intraocular pressure in rabbits. Jpn J Ophthalmol 32:471–480

    Google Scholar 

  15. Gregory D, Sears M, Bausher L, Mishima H, Mead A (1981) Intraocular pressure and aqueous flow are decreased by cholera toxin. Invest Ophthalmol Vis Sci 20: 371–381

    Google Scholar 

  16. Hayashi M, Yablonski ME, Bito LZ (1987) Eicosanoids as a new class of ocular hypotensive agents. 2. Comparison of the apparent mechanism of the ocular hypotensive effects of A- and F-type prostaglandins. Invest Ophthalmol Vis Sci 28:1639–1943

    Google Scholar 

  17. Hayashi M, Yablonski ME, Resul B, Bito LZ (1987) Comparison of the mechanism of the ocular hypotensive effect of PGF2α-1-isopropyl ester, PGA2 and PGA2-1-isopropyl ester on normal and hypotensive cats' eyes. Invest Ophthalmol Vis Sci 28 [ARVO Suppl]:265

    Google Scholar 

  18. Jones RF, Maurice DM (1966) New method of measuring the rate of aqueous flow in man with fluorescein. Exp Eye Res 5:208–220

    Google Scholar 

  19. Kass MA, Podos SM, Moses RA, Becker B (1972) Prostaglandin E1 and aqueous humor dynamics. Invest Ophthalmol 11:1022–1027

    Google Scholar 

  20. Kornbluth W, Linner E (1955) Experimental tonography in rabbits. Arch Ophthalmol 54:717–724

    Google Scholar 

  21. Langham ME (1959) Influence of the intraocular pressure on the formation of the aqueous humour and the outflow resistance in the living eye. Br J Ophthalmol 43:705–732

    Google Scholar 

  22. Langham ME, Edward N (1987) A new procedure for the measurement of the outflow facility in conscious rabbits. Exp Eye Res 45:665–672

    Google Scholar 

  23. Langham ME, Leydhecker W, Krieglstein G, Waller W (1976) Pneumatonographic studies on normal and glaucomatous eyes. Adv Ophthalomol 32:108–133

    Google Scholar 

  24. Lee P, Podos SM, Severin C (1984) Effect of prostaglandin F2α on aqueous humor dynamics of rabbit, cat, and monkey. Invest Ophthalmol Vis Sci 25:1087–1093

    Google Scholar 

  25. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with Folin's phenol reagent. J Biol Chem 193:265–275

    Google Scholar 

  26. Masuda K, Mishima S (1973) Effects of prostaglandins on inflow and outflow of the aqueous humor in rabbits. Jpn J Ophthalmol 17:300–309

    Google Scholar 

  27. Maurice DM, Mishima S (1984) Ocular pharmacokinetics. In: Sears ML (ed) Handbook of experimental pharmacology, vol 69. Springer, Berlin Heidelberg New York, pp 19–116

    Google Scholar 

  28. Mishima S, Masuda K, Tamura T (1977) Drugs influencing aqueous humor formation and drainage. In: Dikstein S (ed) Drugs and ocular tissues. Karger, Basel, pp 128–287

    Google Scholar 

  29. Moses RA, Parkison G, Snower D (1981) Prostaglandin E2 effect on the facility of outflow in the rabbit eye. Ann Ophthalmol 13:721–723

    Google Scholar 

  30. Nakajima M, Goh Y, Azuma I, Hayaishi O (1988) Effects of prostaglandin D2 and BW245C on the human intraocular pressure. Acta Soc Ophthalmol Jpn 92 [Suppl]:121

    Google Scholar 

  31. Narumiya S, Toda N (1985) Different responsiveness of prostaglandin D2-sensitive systems to prostaglandin D2 and its analogues. Br J Pharmacol 85:367–375

    Google Scholar 

  32. Nilsson SFE, Stjernschantz J, Bill A (1987) PGF2α increases uveoscleral outflow. Invest Ophthalmol Vis Sci 28 [ARVO Suppl]:284

    Google Scholar 

  33. Schafer AI, Cooper B, O'Hara D, Handin R (1979) Identification of platelet receptors for prostaglandin I2 and D2. J Biol Chem 254:2914–2917

    Google Scholar 

  34. Suguro K, Toris CB, Pederson JE (1985) Uveoscleral outflow following cyclodialysis in the monkey eye using a fluorescent tracer. Invest Ophthalmol Vis Sci 26:810–813

    Google Scholar 

  35. Toris CB, Pederson JE (1987) Aqueous humor dynamics in experimental iridocyclitis. Invest Ophthalmol Vis Sci 28:477–481

    Google Scholar 

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Authors and Affiliations

  1. Hayaishi Bioinformation Transfer Project, Research Development Corporation of Japan, Kyoto, Japan

    Yasumasa Goh

  2. Department of Ophthalmology, School of Medicine, University of Tokyo, Tokyo, Japan

    Makoto Araie

  3. Department of Ophthalmology, Osaka Medical College, Daigaku-machi, Takatsuki, 569, Osaka, Japan

    Masayuki Nakajima, Ikuo Azuma & Osamu Hayaishi

Authors
  1. Yasumasa Goh
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  2. Makoto Araie
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  3. Masayuki Nakajima
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  4. Ikuo Azuma
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  5. Osamu Hayaishi
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Goh, Y., Araie, M., Nakajima, M. et al. Effect of topical prostaglandin D2 on the aqueous humor dynamics in rabbits. Graefe's Arch Clin Exp Ophthalmol 227, 476–481 (1989). https://doi.org/10.1007/BF02172902

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  • DOI: https://doi.org/10.1007/BF02172902

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