Skip to main content
The British Journal of Ophthalmology logoLink to The British Journal of Ophthalmology
. 2000 Dec;84(12):1411–1414. doi: 10.1136/bjo.84.12.1411

Mechanism related to reduction of intraocular pressure by melanocortins in rabbits

N Naveh 1, A Kaplan-Messas 1, J Marshall 1
PMCID: PMC1723342  PMID: 11090484

Abstract

AIM—To investigate whether the ocular hypotensive effect of alpha melanocyte stimulating hormone (MSH) is related to eicosanoids or cyclic AMP (cAMP).
METHODS—Intraocular pressure (IOP) readings were taken at a similar time on the day before and after a single dose of topical MSH. Changes in the levels of prostaglandin E2 (PGE2) and prostacyclin in incubated iris ciliary body (ICB) explants were measured by specific radioimmunoassay (RIA). Incubated ICB explants were exposed to MSH or adrenaline (epinephrine) for a week. In addition, cAMP levels in the medium were determined following short term incubation using RIA.
RESULTS—A significant dose related reduction in IOP was noted with topical MSH (mean (SD) maximal effect 4.5 (0.1) mm Hg (21%); p<0.001 v appropriate baseline) which persisted up to 6 hours (p=0.05). MSH treated ICB explants showed a 1.5-fold increase in PGE2 and prostacyclin levels (p<0.001 for each parameter) while cAMP levels were increased twofold (p<0.001).
CONCLUSIONS—A single application of MSH caused a sustained dose related ocular hypotensive effect with no side effects. An increase in eicosanoid and cAMP levels following ICB exposure to MSH indicated their involvement in MSH induced ocular hypotension. MSH and its analogues might have clinical relevance as antiglaucoma drugs with fewer side effects because of their antiallergic and anti-inflammatory properties.



Full Text

The Full Text of this article is available as a PDF (130.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abdel-Malek Z. A., Swope V. B., Trinkle L. S., Nordlund J. J. Stimulation of Cloudman melanoma tyrosinase activity occurs predominantly in G2 phase of the cell cycle. Exp Cell Res. 1989 Jan;180(1):198–208. doi: 10.1016/0014-4827(89)90224-3. [DOI] [PubMed] [Google Scholar]
  2. Ariëns E. J. Receptors and dormant receptors--messengers and opportunistic ligands. J Recept Res. 1991;11(1-4):1–11. doi: 10.3109/10799899109066386. [DOI] [PubMed] [Google Scholar]
  3. Bar-Ilan A., Savion N., Naveh N., Ilan A. B. Alpha melanocyte stimulating hormone (alpha-MSH) enhances eicosanoid production by bovine retinal pigment epithelium. Prostaglandins. 1992 Jan;43(1):31–44. doi: 10.1016/0090-6980(92)90062-x. [DOI] [PubMed] [Google Scholar]
  4. Bauer B., Ehinger B. Action of alpha-MSH on the release of neurotransmitters from the retina. Acta Physiol Scand. 1980 Jan;108(1):105–107. doi: 10.1111/j.1748-1716.1980.tb06506.x. [DOI] [PubMed] [Google Scholar]
  5. Bengtsson E., Ehinger B. The effect of experimental uveitis on the uptake of prostaglandin E1 in the rabbit iris-ciliary body. Acta Ophthalmol (Copenh) 1977 Aug;55(4):688–695. doi: 10.1111/j.1755-3768.1977.tb05667.x. [DOI] [PubMed] [Google Scholar]
  6. Bengtsson E. The effect of imidazole on the disruption of the blood-aqueous barrier in the rabbit eye. Invest Ophthalmol. 1976 Apr;15(4):315–320. [PubMed] [Google Scholar]
  7. Bengtsson E. The effect of theophylline on the breakdown of the blood-aqueous barrier in the rabbit eye. Invest Ophthalmol Vis Sci. 1977 Jul;16(7):636–640. [PubMed] [Google Scholar]
  8. Bito L. Z. Prostaglandins: a new approach to glaucoma management with a new, intriguing side effect. Surv Ophthalmol. 1997 Feb;41 (Suppl 2):S1–14. doi: 10.1016/s0039-6257(97)80002-1. [DOI] [PubMed] [Google Scholar]
  9. Camras C. B., Schumer R. A., Marsk A., Lustgarten J. S., Serle J. B., Stjernschantz J., Bito L. Z., Podos S. M. Intraocular pressure reduction with PhXA34, a new prostaglandin analogue, in patients with ocular hypertension. Arch Ophthalmol. 1992 Dec;110(12):1733–1738. doi: 10.1001/archopht.1992.01080240073034. [DOI] [PubMed] [Google Scholar]
  10. Ceriani G., Macaluso A., Catania A., Lipton J. M. Central neurogenic antiinflammatory action of alpha-MSH: modulation of peripheral inflammation induced by cytokines and other mediators of inflammation. Neuroendocrinology. 1994 Feb;59(2):138–143. doi: 10.1159/000126650. [DOI] [PubMed] [Google Scholar]
  11. Clark D., Thody A. J., Shuster S., Bowers H. Immunoreactive alpha-MSH in human plasma in pregnancy. Nature. 1978 May 11;273(5658):163–164. doi: 10.1038/273163a0. [DOI] [PubMed] [Google Scholar]
  12. Crosson C. E. Adenosine receptor activation modulates intraocular pressure in rabbits. J Pharmacol Exp Ther. 1995 Apr;273(1):320–326. [PubMed] [Google Scholar]
  13. DYSTER-AAS H. K., KRAKAU C. E. A PHOTO-ELECTRIC INSTRUMENT FOR MEASURING THE AQUEOUS FLARE IN THE INTACT EYE. Ophthalmologica. 1963;146:48–56. doi: 10.1159/000304497. [DOI] [PubMed] [Google Scholar]
  14. DYSTER-AAS H. K., KRAKAU C. E. GENERAL EFFECTS OF ALPHA-MELANOCYTE STIMULATING HORMONE IN THE RABBIT. Acta Endocrinol (Copenh) 1965 Apr;48:609–618. doi: 10.1530/acta.0.0480609. [DOI] [PubMed] [Google Scholar]
  15. DYSTER-AAS K., KRAKAU C. E. INCREASED PERMEABILITY OF THE BLOOD-AQUEOUS HUMOR BARRIER IN THE RABBIT'S EYE PROVOKED BY MELANOCYTE STIMULATING PEPTIDES. Endocrinology. 1964 Feb;74:255–265. doi: 10.1210/endo-74-2-255. [DOI] [PubMed] [Google Scholar]
  16. Dyster-Aas H. K., Kastin A. J., Vidacovich R. P., Schally A. V. Melanocyte-stimulating activity in serum and the aqueous flare response in rabbits. J Endocrinol. 1970 Feb;46(2):285–286. doi: 10.1677/joe.0.0460285. [DOI] [PubMed] [Google Scholar]
  17. Goland R. S., Conwell I. M., Warren W. B., Wardlaw S. L. Placental corticotropin-releasing hormone and pituitary-adrenal function during pregnancy. Neuroendocrinology. 1992 Nov;56(5):742–749. doi: 10.1159/000126302. [DOI] [PubMed] [Google Scholar]
  18. Goodall T., Buffey J. A., Rennie I. G., Benson M., Parsons M. A., Faulkner M. K., MacNeil S. Effect of melanocyte stimulating hormone on human cultured choroidal melanocytes, uveal melanoma cells, and retinal epithelial cells. Invest Ophthalmol Vis Sci. 1994 Mar;35(3):826–837. [PubMed] [Google Scholar]
  19. Gunn T. M., Miller K. A., He L., Hyman R. W., Davis R. W., Azarani A., Schlossman S. F., Duke-Cohan J. S., Barsh G. S. The mouse mahogany locus encodes a transmembrane form of human attractin. Nature. 1999 Mar 11;398(6723):152–156. doi: 10.1038/18217. [DOI] [PubMed] [Google Scholar]
  20. Hernandez D. E., Simons K. B., Spampinato D., Peiffer R. L., Jr, Drago F. Intracameral administration of alpha-MSH increases intraocular pressure in rabbits. Neuropeptides. 1985 Dec;6(6):553–559. doi: 10.1016/0143-4179(85)90118-0. [DOI] [PubMed] [Google Scholar]
  21. Hiltz M. E., Catania A., Lipton J. M. Alpha-MSH peptides inhibit acute inflammation induced in mice by rIL-1 beta, rIL-6, rTNF-alpha and endogenous pyrogen but not that caused by LTB4, PAF and rIL-8. Cytokine. 1992 Jul;4(4):320–328. doi: 10.1016/1043-4666(92)90073-z. [DOI] [PubMed] [Google Scholar]
  22. Holmdahl G., Bengtsson E. The effect of timolol maleate on the disruption of the blood-aqueous barrier in the rabbit eye. Invest Ophthalmol Vis Sci. 1981 Jun;20(6):726–732. [PubMed] [Google Scholar]
  23. Hunt G. Melanocyte-stimulating hormone: a regulator of human melanocyte physiology. Pathobiology. 1995;63(1):12–21. doi: 10.1159/000163930. [DOI] [PubMed] [Google Scholar]
  24. Hyatt P. J., Bell J. B., Bhatt K., Chu F. W., Tait J. F., Tait S. A., Whitley G. S. Effects of alpha-melanocyte-stimulating hormone on the cyclic AMP and phospholipid metabolism of rat adrenocortical cells. J Endocrinol. 1986 Sep;110(3):405–416. doi: 10.1677/joe.0.1100405. [DOI] [PubMed] [Google Scholar]
  25. Kastin A. J., Beach G. D., Hawley W. D., Kendall J. W., Jr, Edwards M. S., Schally A. V. Dissociation of MSH and ACTH release in man. J Clin Endocrinol Metab. 1973 Apr;36(4):770–772. doi: 10.1210/jcem-36-4-770. [DOI] [PubMed] [Google Scholar]
  26. Kastin A. J., Kullander S., Borglin N. E., Dahlberg B., Dyster-Aas K., Krakau C. E., Ingvar D. H., Miller M. C., 3rd, Bowers C. Y., Schally A. V. Extrapigmentary effects of melanocyte-stimulating hormone in amenorrhoeic women. Lancet. 1968 May 11;1(7550):1007–1010. doi: 10.1016/s0140-6736(68)91113-6. [DOI] [PubMed] [Google Scholar]
  27. Knisely T. L., Hosoi J., Nazareno R., Granstein R. D. The presence of biologically significant concentrations of glucocorticoids but little or no cortisol binding globulin within aqueous humor: relevance to immune privilege in the anterior chamber of the eye. Invest Ophthalmol Vis Sci. 1994 Sep;35(10):3711–3723. [PubMed] [Google Scholar]
  28. Macaluso A., McCoy D., Ceriani G., Watanabe T., Biltz J., Catania A., Lipton J. M. Antiinflammatory influences of alpha-MSH molecules: central neurogenic and peripheral actions. J Neurosci. 1994 Apr;14(4):2377–2382. doi: 10.1523/JNEUROSCI.14-04-02377.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Mauri A., Volpe A., Martellotta M. C., Barra V., Piu U., Angioni G., Angioni S., Argiolas A. alpha-Melanocyte-stimulating hormone during human perinatal life. J Clin Endocrinol Metab. 1993 Jul;77(1):113–117. doi: 10.1210/jcem.77.1.8392079. [DOI] [PubMed] [Google Scholar]
  30. Naveh N., Muchtar S., Benita S. Pilocarpine incorporated into a submicron emulsion vehicle causes an unexpectedly prolonged ocular hypotensive effect in rabbits. J Ocul Pharmacol. 1994 Fall;10(3):509–520. doi: 10.1089/jop.1994.10.509. [DOI] [PubMed] [Google Scholar]
  31. Phillips C. I., Gore S. M. Ocular hypotensive effect of late pregnancy with and without high blood pressure. Br J Ophthalmol. 1985 Feb;69(2):117–119. doi: 10.1136/bjo.69.2.117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Qureshi I. A. Intraocular pressure and pregnancy: a comparison between normal and ocular hypertensive subjects. Arch Med Res. 1997 Autumn;28(3):397–400. [PubMed] [Google Scholar]
  33. Qureshi I. A., Xi X. R., Wu X. D. Intraocular pressure trends in pregnancy and in the third trimester hypertensive patients. Acta Obstet Gynecol Scand. 1996 Oct;75(9):816–819. doi: 10.3109/00016349609054709. [DOI] [PubMed] [Google Scholar]
  34. Schiöth H. B., Muceniece R., Wikberg J. E. Characterization of the binding of MSH-B, HB-228, GHRP-6 and 153N-6 to the human melanocortin receptor subtypes. Neuropeptides. 1997 Dec;31(6):565–571. doi: 10.1016/s0143-4179(97)90002-0. [DOI] [PubMed] [Google Scholar]
  35. Taylor A. W., Streilein J. W., Cousins S. W. Identification of alpha-melanocyte stimulating hormone as a potential immunosuppressive factor in aqueous humor. Curr Eye Res. 1992 Dec;11(12):1199–1206. doi: 10.3109/02713689208999545. [DOI] [PubMed] [Google Scholar]
  36. Yousufzai S. Y., Zheng P., Abdel-Latif A. A. Muscarinic stimulation of arachidonic acid release and prostaglandin synthesis in bovine ciliary muscle: prostaglandins induce cyclic AMP formation and muscle relaxation. Exp Eye Res. 1994 May;58(5):513–522. doi: 10.1006/exer.1994.1045. [DOI] [PubMed] [Google Scholar]

Articles from The British Journal of Ophthalmology are provided here courtesy of BMJ Publishing Group

RESOURCES