Mechanism Related to Reduction of Intraocular Pressure by Melanocortins in Rabbits

Overview

Journal Br J Ophthalmol

Specialty Ophthalmology

Date 2000 Nov 25

PMID 11090484

Citations 3

Authors

N Naveh

A Kaplan-Messas

J Marshall

Affiliations

Soon will be listed here.

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 E(2) (PGE(2)) 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 PGE(2) 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.

Citing Articles

Therapeutic Effect of α-MSH in Primary Cultured Orbital Fibroblasts Obtained from Patients with Thyroid Eye Disease.

Cheng P, Tsai P, Tai M, Bee Y Int J Mol Sci. 2021; 22(20).

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The Role of Alpha-MSH as a Modulator of Ocular Immunobiology Exemplifies Mechanistic Differences between Melanocortins and Steroids.

Clemson C, Yost J, Taylor A Ocul Immunol Inflamm. 2016; 25(2):179-189.

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Applications of the role of α-MSH in ocular immune privilege.

Taylor A, Lee D Adv Exp Med Biol. 2011; 681:143-9.

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References

Goland R, Conwell I, Warren W, Wardlaw S . Placental corticotropin-releasing hormone and pituitary-adrenal function during pregnancy. Neuroendocrinology. 1992; 56(5):742-9. DOI: 10.1159/000126302. View

Camras C, Schumer R, Marsk A, Lustgarten J, Serle J, Stjernschantz J . Intraocular pressure reduction with PhXA34, a new prostaglandin analogue, in patients with ocular hypertension. Arch Ophthalmol. 1992; 110(12):1733-8. DOI: 10.1001/archopht.1992.01080240073034. View

Mauri A, Volpe A, Martellotta M, Barra V, Piu U, Angioni G . alpha-Melanocyte-stimulating hormone during human perinatal life. J Clin Endocrinol Metab. 1993; 77(1):113-7. DOI: 10.1210/jcem.77.1.8392079. View

Goodall T, Buffey J, Rennie I, Benson M, Parsons M, Faulkner M . Effect of melanocyte stimulating hormone on human cultured choroidal melanocytes, uveal melanoma cells, and retinal epithelial cells. Invest Ophthalmol Vis Sci. 1994; 35(3):826-37. View

Ceriani G, Macaluso A, Catania A, Lipton J . Central neurogenic antiinflammatory action of alpha-MSH: modulation of peripheral inflammation induced by cytokines and other mediators of inflammation. Neuroendocrinology. 1994; 59(2):138-43. DOI: 10.1159/000126650. View

Macaluso A, Mccoy D, Ceriani G, Watanabe T, Biltz J, Catania A . Antiinflammatory influences of alpha-MSH molecules: central neurogenic and peripheral actions. J Neurosci. 1994; 14(4):2377-82. PMC: 6577153. View

Knisely T, Hosoi J, Nazareno R, Granstein R . 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; 35(10):3711-23. View

Yousufzai S, Zheng P, Abdel-Latif 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; 58(5):513-22. DOI: 10.1006/exer.1994.1045. View

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; 10(3):509-20. DOI: 10.1089/jop.1994.10.509. View

10.

Crosson C . Adenosine receptor activation modulates intraocular pressure in rabbits. J Pharmacol Exp Ther. 1995; 273(1):320-6. View

11.

Hunt G . Melanocyte-stimulating hormone: a regulator of human melanocyte physiology. Pathobiology. 1995; 63(1):12-21. DOI: 10.1159/000163930. View

12.

Qureshi I, Xi X, Wu X . Intraocular pressure trends in pregnancy and in the third trimester hypertensive patients. Acta Obstet Gynecol Scand. 1996; 75(9):816-9. DOI: 10.3109/00016349609054709. View

13.

Bito L . Prostaglandins: a new approach to glaucoma management with a new, intriguing side effect. Surv Ophthalmol. 1997; 41 Suppl 2:S1-14. DOI: 10.1016/s0039-6257(97)80002-1. View

14.

Qureshi I . Intraocular pressure and pregnancy: a comparison between normal and ocular hypertensive subjects. Arch Med Res. 1997; 28(3):397-400. View

15.

Schioth H, Muceniece R, Wikberg J . Characterization of the binding of MSH-B, HB-228, GHRP-6 and 153N-6 to the human melanocortin receptor subtypes. Neuropeptides. 1998; 31(6):565-71. DOI: 10.1016/s0143-4179(97)90002-0. View

16.

Gunn T, Miller K, He L, HYMAN R, Davis R, Azarani A . The mouse mahogany locus encodes a transmembrane form of human attractin. Nature. 1999; 398(6723):152-6. DOI: 10.1038/18217. View

17.

DYSTER-AAS H, KRAKAU C . GENERAL EFFECTS OF ALPHA-MELANOCYTE STIMULATING HORMONE IN THE RABBIT. Acta Endocrinol (Copenh). 1965; 48:609-18. DOI: 10.1530/acta.0.0480609. View

18.

DYSTER-AAS H, KRAKAU C . A PHOTO-ELECTRIC INSTRUMENT FOR MEASURING THE AQUEOUS FLARE IN THE INTACT EYE. Ophthalmologica. 1963; 146:48-56. DOI: 10.1159/000304497. View

19.

DYSTER-AAS K, KRAKAU C . INCREASED PERMEABILITY OF THE BLOOD-AQUEOUS HUMOR BARRIER IN THE RABBIT'S EYE PROVOKED BY MELANOCYTE STIMULATING PEPTIDES. Endocrinology. 1964; 74:255-65. DOI: 10.1210/endo-74-2-255. View

20.

Kastin A, Kullander S, BORGLIN N, DAHLBERG B, DYSTER-AAS K, KRAKAU C . Extrapigmentary effects of melanocyte-stimulating hormone in amenorrhoeic women. Lancet. 1968; 1(7550):1007-10. DOI: 10.1016/s0140-6736(68)91113-6. View