Mechanism related to reduction of intraocular pressure by melanocortins in rabbits.
OBJECTIVE
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.
Naveh
N
N
Goldschleger Eye Research Institute, Tel Aviv University School of Medicine, Sheba Medical Center, Israel. hnave@zahav@net.il
Kaplan-Messas
A
A
Marshall
J
J
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D002924:Ciliary Body / Q000187:drug effects / Q000378:metabolism; D046508:Culture Techniques; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D007429:Intraocular Pressure / Q000187:drug effects* / Q000502:physiology; D008297:Male; D011817:Rabbits; D011897:Random Allocation; D000521:alpha-MSH / Q000494:pharmacology*
D000521:alpha-MSH; D015121:6-Ketoprostaglandin F1 alpha; D000242:Cyclic AMP; D015232:Dinoprostone