Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Prostaglandins and ocular inflammation

  • 60 Accesses

  • 5 Citations

Abstract

Evidence for prostaglandins as mediators of some inflammatory responses is briefly, but critically discussed. The hypothesis that prostaglandins are mediators of ocular inflammation is presented and discussed according to the tenets of Miller & Melmon (1970). Prostaglandins are released after mechanical stimulation, paracentesis, laser irradiation, (non)-immunogenic uveitis in experimental animals, and in patients with acute anterior uveitis. Prostaglandins were neither found after antidromic stimulation of the trigeminal nerve, oculomotor nerve stimulation, intracameral formaldehyde, topical nitrogen mustard, nor in patients with open angle glaucoma.

Administering of prostaglandins produces transient ocular hypertension, increased vascular permeability and miosis. Ocular hypotension has been shown to follow the hypertensive response. Hypertension is considered to be due to a breakdown of the blood-aqueous barrier of the ciliary processes and iris. Prostaglandins of the E series are the most potent, and species differences occur. Prostaglandin E1 potentiates the histamine-induced increase in vascular permeability of the conjunctiva, but not the uvea. Polyphloretin phosphate aspecifically blocks the ocular actions of prostaglandins. Non-steroidal anti-inflammatory drugs inhibit prostaglandin synthetase and the ocular effects of arachidonic acid, its substrate. Prostaglandins are poorly catabolised by the eye, but are removed from ocular fluids by a transport mechanism in the anterior uvea. This becomes inoperative in (non)-immunogenic uveitis in rabbits allowing prostaglandins to accumulate. Anti-inflammatory steroids decrease the availability of arachidonic acid for prostaglandin synthetase. Intermediates formed in the biosynthesis of prostaglandins may well be more important in inflammation than the prostaglandins themselves.

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

References

  1. Ambache, N. Properties of irin, a physiological constituent of the rabbit's iris. J. Physiol. London 135: 114–132 (1957).

  2. Ambache, N. & H.C. Brummer. A simple chemical procedure for distinguishing E from F prostaglandins, with application to tissue extracts. Brit. J. Pharmacol. 33: 162–170 (1968).

  3. Ambache, N., H.C. Brummer, J.G. Rose & J. Whiting. Thin layer chromatography of spasmogenic unsaturated hydroxy-acids from various tissues. J. Physiol. London 185: 77–78P (1966).

  4. Ambache, N., L. Kavanagh & J. Whiting. Effect of mechanical stimulation on rabbit's eyes: release of active substance in anterior chamber perfusates. J. Physiol. London 176: 378–408 (1965).

  5. Ånggard, E. & B. Samuelsson. Smooth muscle stimulating lipids in sheep iris. The identification of prostaglandin 431–01. Biochem. Pharmacol. 13: 281–283 (1964).

  6. Beitch, B.R. & K.E. Eakins. The effects of prostaglandins on the intraocular pressure of the rabbit. Brit. J. Pharmacol. 37: 158–167 (1969).

  7. Bergström, S., L.A. Carlson & J.R. Weeks. The prostaglandins: A family of biologically active lipids. Pharmacol. Rev. 20: 1–48 (1968).

  8. Bethel, R.A. & K.E. Eakins. The mechanism of the antagonism of experimentally induced ocular hypertension by polyphloretin phosphate. Exp. Eye Res. 13: 83–91 (1971).

  9. Bhattacherjee, P. Release of prostaglandin-like substances by Shigella endotoxin and its inhibition by non-steroidal anti-inflammatory compounds. Brit. J. Pharmacol. 54: 489–494 (1975).

  10. Bhattacherjee, P. Stimulation of prostaglandin synthetase activity in inflamed ocular tissue of the rabbit. Exp. Eye Res. 24: 215–216 (1977).

  11. Bhattacherjee, P. & K.E. Eakins. Inhibition of the prostaglandin synthetase systems in ocular tissues by indomethacin. Brit. J. Pharmacol. 50: 227–230 (1974a).

  12. Bhattacherjee, P. & K.E. Eakins. A comparison of the inhibitory activity of compounds on ocular prostaglandin biosynthesis. Invest. Ophthal. 14: 967–972 (1974b).

  13. Bhattacherjee, P. & K.E. Eakins. Inhibition of the ocular effects of sodium arachidonate by anti-inflammatory compounds. Prostaglandins 9: 175–182 (1975).

  14. Bhattacherjee, P. & B.R. Hammond. Inhibition of increased permeability of the blood-aqueous barrier by non-steroidal anti-inflammatory compounds as demonstrated by fluorescein angiography. Exp. Eye Res. 21: 499–505 (1975).

  15. Bhattacherjee, P. & B.R. Hammond. Effect of indomethacin on the ocular action of adrenaline in the rabbit. Exp. Eye Res. 24: 307–313 (1977).

  16. Bito, L.Z. The effects of experimental uveitis on anterior uveal prostaglandin transport and aqueous humour composition. Invest. Ophthal. 13: 959–965 (1974).

  17. Bito, L.Z. & E.V. Salvador. Intraocular fluid dynamics. III. The site and mechanism of prostaglandin transfer across the blood intraocular fluid barriers. Exp. Eye Res. 14: 233–241 (1972).

  18. Bonta, I.L., H. Bult, L.L.M. van der Ven & J. Noordhoek. Essential fatty acid deficiency: A condition to discriminate prostaglandin and non-prostaglandin mediated components of inflammation. Agents and Actions 6: 154–158 (1976).

  19. Bonta, I.L., M.J. Parnham, M.J.P. Adolfs & L. van Vliet. Dual function of E-type prostaglandins in models of chronic inflammation. Paper presented at Future Trends in Inflammation III, London, February 14–18, 1977.

  20. Casey, W. J. The effect of prostaglandin E2 on the rhesus monkey pupil. Prostaglandins 6: 243–251 (1974).

  21. Chiang, T.S. Effects of intravenous infusions of histamine, 5-hydroxytryptamine, bradykinin and prostaglandins on intraocular pressure. Arch. Int. Pharmacodyn. 207: 131–138 (1974).

  22. Cole, D.F. Prevention of experimental ocular hypertension with polyphloretin phosphate. Brit. J. Ophthal. 45: 482–489 (1961).

  23. Cole, D. F. The site of breakdown of the blood-aqueous barrier under the influence of vaso-dilator drugs. Exp. Eye Res. 19: 591–607 (1974).

  24. Cole, D.F. & W.G. Ungar. Prostaglandins as mediators for the responses of the eye to trauma. Exp. Eye Res. 17: 357–368 (1973).

  25. Conquet, Ph., B. Plazonnet & J.C. LeDouarec. Arachidonic acid-induced elevation of intraocular pressure and anti-inflammatory agents. Invest. Ophthal. 14: 772–775 (1975).

  26. Crunkhorn, P. & A.L. Willis. Actions and interactions of prostaglandins administered intradermally in rat and man. Brit. J. Pharmacol. 36: 216 P (1969).

  27. Dellow, P.G. & T.S. Miles. Meiosis: A prostaglandin response that is not inhibited by aspirin. Brit. J. Pharmacol. 55: 157–159 (1975).

  28. Eakins, K.E. Increased intraocular pressure produced by prostaglandins E1 and E2 in the cat eye. Exp. Eye Res. 10: 87–92 (1970).

  29. Eakins, K.E., M. Atwal & P. Bhattacherjee. Inactivation of prostaglandin E1 by ocular tissues in vitro Exp. Eye Res. 19: 141–146 (1974).

  30. Eakins, K.E. & P. Bhattacherjee. Histamine, prostaglandins and ocular inflammation. Exp. Eye Res. 24: 299–305 (1977).

  31. Eakins, K.E., R.A.F. Whitelocke, E.S. Perkins, A. Bennett & W.G. Ungar. Release of prostaglandins in ocular inflammation in the rabbit. Nature New Biology 239: 248–249 (1972a).

  32. Eakins, K.E., R.A.F. Whitelocke, A. Bennett & A.C. Martenet. Prostaglandin-like activity in ocular inflammation. Brit. Med. J. 3: 452–453 (1972b).

  33. Feldberg, W. & P.N. Saxena. Further studies on prostaglandin E1 fever in cats. J. Physiol. London 219: 739–746 (1972).

  34. Ferreira, S.H. Prostaglandins, aspirin-like drugs and analgesia. Nature New Biology 240: 200–203 (1972).

  35. Floman, N. & U. Zor. Mechanism of steroid action in ocular inflammation. Inhibition of prostaglandin production. Invest. Ophthal. 16: 69–73 (1977).

  36. Flower, R.D. Drugs which inhibit prostaglandin biosynthesis. Pharmacol. Rev. 26: 33–66 (1974).

  37. Greaves, M.W., J. Søndergaard & W. McDonald-Gibson. Recovery of prostaglandins in human cutaneous inflammation. Brit. Med. J. 2: 258–260 (1971).

  38. Green, J. & K. Kim. Pattern of ocular response to topical and systemic prostaglandin. Invest. Ophthal. 14: 36–40 (1975).

  39. Gryglewski, R.J., B. Panczenko, R. Korbut, L. Grodsinska & A. Ocetkiewicz. Corticosteroids inhibit prostaglandin release from perfused mesenteric blood vessels of rabbit and from perfused lungs of sensitized guinea-pig. Prostaglandins 10: 343–355 (1975).

  40. Hall, D.W.R. & K.D. Jaitly. Inflammatory responses of the rabbit eye to prostaglandins. Agents and Actions. Suppl. 2: 123–134 (1977).

  41. Hamberg, M., J. Svensson & B. Samuelsson. Thromboxanes; A group of biologically active compounds derived from prostaglandin endoperoxides. Proc. Nat. Acad. Sci. USA 72: 2994–2998 (1975).

  42. Horton, E.W. Action of prostaglandin E1 on tissues which respond to bradykinin. Nature London 200: 892–893 (1963).

  43. Horton, E.W. Biological activities of pure prostaglandins. Experientia 21: 113–118 (1965).

  44. Jaffe, B.M., S.M. Podos & B. Becker. Indomethacin blocks arachidonic acid-associated elevation of aqueous humor prostaglandin E. Invest. Ophthal 12: 621–622 (1973).

  45. Jampol, L.M., A.H. Neufeld & M. L. Sears. Pathways for the response of the eye to injury. Invest. Ophthal. 14: 184–189 (1975).

  46. Kadowitz, P.J., P.D. Joiner & A.L. Hyman. Physiological and pharmacological roles of prostaglandins. Ann. Rev. Pharmacol. 15: 285–306 (1975).

  47. Kaley, G. & R. Weiner. Microcirculatory studies with prostaglandin E1. In: Prostaglandin Symposium of the Worcester Foundation for Experimental Biology. Eds. Ramwell, P.W. & Shaw, J.E. New York, Interscience 321 (1968).

  48. Kaley, G. & R. Weiner. Effect of prostaglandin E1 on leucocyte migration. Nature New Biology 234: 114–115 (1971).

  49. Karim, S.M.M. & G.M. Filshie. Use of prostaglandin E2 for therapeutic abortion. Brit. Med. J. 3: 198–200 (1970).

  50. Karim, S.M.M. & K. Hillier. Prostaglandins: Pharmacology and clinical application. Drugs 8: 176–207 (1974).

  51. Kass, M.A., S.M. Podos, R.A. Moses & B. Becker. Prostaglandin E1 and aqueous humour dynamics. Invest. Ophthal 11: 1022–1027 (1972).

  52. Kelly, R.G.M. & M.S. Starr. Effects of prostaglandins and a prostaglandin antagonist on intraocular pressure and protein in the monkey eye. Canad. J. Ophthal. 6: 205–211 (1971).

  53. Kuehl Jr., F. A., J.L. Humes, R.W. Egan, E. A. Ham, G.C. Beveridge & C.G. van Arman. Role of prostaglandin endoperoxide PGG2 in inflammatory processes. Nature London 265: 170–173 (1977).

  54. Lewis, G.P. Role of kinins and prostaglandins as mediators of functional hyperaemia. Proc. R. Soc. Med. 64: 6–9 (1971).

  55. Lewis, G.P. & P.J. Piper. Inhibition of release of prostaglandins as an explanation of some of the actions of anti-inflammatory corticosteroids. Nature London 254: 308–311 (1975).

  56. Meyers, R. L. & T.H. Pettit. Chemotaxis of polymorphonuclear leukocytes in corneal inflammation: tissue injury in Herpes simplex virus infection. Invest. Ophthal. 13: 187–197 (1974).

  57. Miller, J.D., K.E. Eakins & M. Atwal. The release of PGE2-like activity into aqueous humor after paracentesis and its prevention by aspirin. Invest. Ophthal. 12: 939–942 (1973).

  58. Miller, R.L. & K.L. Melmon. The related roles of histamine, serotonin and bradykinin in the pathogenesis of inflammation. Ser. Haemat. 3: 5–38 (1970).

  59. Milton, A. S. Prostaglandin PGE1 and endotoxin fever, and the effect of aspirin, indomethacin and 4-acetamidophenol. In: Advances in the Biosciences, Pergamon Press, Oxford 9: 495–500 (1973).

  60. Moncada, S., S.H. Ferreira & J.R. Vane. Prostaglandins, aspirin-like drugs and the oedema of inflammation. Nature London 246: 217–219 (1973).

  61. Morley, I. Interactions between lymphocytes and macrophages. Agents and Actions (in press).

  62. Neufeld, A.H., D.K. Dueker, T. Vegge & M.L. Sears. Adenosine 3′,5′-monophosphate increases the outflow of aqueous humor from the rabbit eye. Invest. Ophthal 14: 40–42 (1975).

  63. Neufeld, A.H., L.M. Jampol & M.L. Sears. Aspirin prevents the disruption of the blood-aqueous barrier in the rabbit eye. Nature London 238: 158–159 (1972a).

  64. Neufeld, A.H., L.M. Jampol & M.L. Sears. Cyclic-AMP in the aqueous humor: The effects of adrenergic agents. Exp. Eye Res. 14: 242–250 (1972b).

  65. Neufeld, A.H. & M.L Sears. Prostaglandin and the eye. Prostaglandins 4: 157–175 (1973).

  66. Neufeld, A.H. & M.L. Sears. Cyclic-AMP in ocular tissues of the rabbit, monkey, and human. Invest. Ophthal. 13: 475–477 (1974).

  67. Nijkamp, F.P., R.J. Flower, S. Moncada & J.R. Vane. Partial purification of rabbit aorta contracting substance-releasing factor and inhibition of its activity by anti-inflammatory steroids. Nature London 263: 479–482 (1976).

  68. Paterson, C.A. & R.R. Pfister. Prostaglandin-like activity in the aqueous humor following alkali burns. Invest. Ophthal. 14: 177–183 (1975).

  69. Perkins, E.S. Prostaglandins and the eye. Adv. Ophthal. 29: 2–21 (1975).

  70. Podos, S.M. & B. Becker. Prostaglandins and the eye. Symposium on Ocular Therapy 7: 96–103 (1974).

  71. Podos, S.M. & B. Becker. Comparison of ocular prostaglandin synthesis inhibitors. Invest. Ophthal. 15: 841–844 (1976).

  72. Podos, S.M., B. Becker & M.A. Kass. Prostaglandin synthesis, inhibition, and intraocular pressure. Invest. Ophthal. 12: 426–433 (1973).

  73. Podos, S.M., B.M. Jaffe & B. Becker. Prostaglandins and glaucoma. Brit. Med. J. 4: 232 (1972).

  74. Rosenthale, M.E., A. Dervinis, J. Kassarich & S. Singer. Prostaglandins and anti-inflammatory drugs in the dog knee joint. J. Pharm. Pharmacol. 24: 149–150 (1972).

  75. Solomon, L.M., L. Juhlin & M.B. Kirschenbaum. Prostaglandin on cutaneous vasculature. J. Invest. Dermatol. 51: 280–282 (1968).

  76. Smith, M.J.H. Prostaglandins and aspirin: An alternative view. Agents and actions 5: 315–317 (1975).

  77. Starr, M.S. Further studies on the effect of prostaglandin on intraocular pressure in the rabbit. Exp. Eye Res. 11: 170–177 (1971).

  78. Stjernschantz, J., A. Alm & A. Bill. Effects of intracranial oculomotor nerve stimulation on ocular blood flow in rabbits: Modification by indomethacin. Exp. Eye Res. 23: 461–469 (1976).

  79. Szalay, J., R. Goldberg & R. Klug. The effect of prostaglandin on iridial blood vessel permeability. Acta Ophthal. (Kbh) 54: 731–742 (1976).

  80. Taylor, P.L. & R.W. Kelly. 19-Hydroxylated E prostaglandins as the major prostaglandins of human semen. Nature London 250: 665–667 (1974).

  81. Ungar, W.G., D.F. Cole & B.R. Hammond. Disruption of the blood-aqueous barrier following paracentesis in the rabbit. Exp. Eye Res. 20: 255–270 (1975).

  82. Ungar, W.G., E.S. Perkins & M.S. Bass. The response of the rabbit eye to laser irridiation of the iris. Exp. Eye Res. 19: 367–377 (1974).

  83. Vane, J.R. Inhibition of prostaglandin biosynthesis as a mechanism of action of aspirin-like drugs. In: Advances in the Biosciences, Pergamon Press, Oxford 9: 395–411 (1973).

  84. Waitzman, M.B. Influences of prostaglandin and adrenergic drugs on ocular pressure and pupil size. In: Prostaglandin Symposium of the Worcester Foundation for Experimental Biology, Eds. Ramwell, P.W. & Shaw, J.E. Interscience, New York 335–349 (1968).

  85. Waitzman, M.B. Possible new concepts relating prostaglandins in various ocular functions. Sun. Ophthal. 14: 301–326 (1970).

  86. Waitzman, M.B. & C.D. King. Prostaglandin influences on intraocular pressure and pupil size. Am. J. Physiol. 212: 329–334 (1967).

  87. Waitzman, M.B. & C.D. Woods. Some characteristics of an adenyl cyclase preparation from rabbit ciliary processes. Exp. Eye Res. 12: 99–111 (1971).

  88. Whitelocke, R.A.F. & K.E. Eakins. Vascular changes in the anterior uvea of the rabbit produced by prostaglandins. Arch. Ophthal. 89: 495–499 (1973).

  89. Williams, T.J. & J. Morley. Prostaglandins as potentiators of increased vascular permeability in inflammation. Nature London 246: 215–217 (1973).

  90. Willis, A.L. Parallel assay of prostaglandin-like activity in rat inflammatory exudate by means of cascade superfusion. J. Pharm. Pharmacol. 21: 126–128 (1969).

  91. Willoughby, D.A. & P. Dieppe. Prostaglandins in the inflammatory response - pro or anti? In: The role of prostaglandins in inflammation. Ed. Lewis, G.P., Hans Huber Publishers, Bern, pp. 74–25 (1976).

  92. Wyllie, A.M. & L.H. Wyllie. Prostaglandins and glaucoma. Brit. Med. J. 3: 615–617 (1971).

  93. Zink, H.A., S.M. Podos & B. Becker. Inhibition by imidazole of the increase in intraocular pressure induced by topical prostaglandin E. Nature London 245: 21–22 (1973).

Download references

Author information

Additional information

Part of this review was presented at the 171st Congress of the Dutch Ophthalmological Society.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Hall, D.W.R., Bonta, I.L. Prostaglandins and ocular inflammation. Doc Ophthalmol 44, 421–434 (1977). https://doi.org/10.1007/BF00230091

Download citation

Keywords

  • Blood-aqueous barrier
  • Corticosteroids
  • Ocular inflammation
  • Ocular hypertension
  • Prostaglandins
  • Non-steroidal anti-inflammatory drugs