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Further studies on ocular responses to DP receptor stimulation
D F Woodward1, C S Spada, S B Hawley
1Department of Biological Sciences, Allergan, Inc., Irvine, CA 92713-9534.
European Journal of Pharmacology
|January 19, 1993
Summary
Selective DP receptor agonists, like SQ 27986, effectively lower intraocular pressure without causing ocular surface damage. Prostaglandin D2 (PGD2) effects are mediated by the DP receptor, but its ocular side effects may involve other pathways.
Area of Science:
- Ophthalmology
- Pharmacology
- Ocular Surface Disease
Background:
- Prostaglandin D2 (PGD2) lowers intraocular pressure (IOP) but causes ocular side effects.
- Selective DP receptor agonists offer a potential therapeutic advantage for managing IOP.
Purpose of the Study:
- To further define the ocular pharmacology of PGD2 using selective DP receptor agonists and antagonists.
- To investigate the role of the DP receptor in PGD2-induced ocular effects and IOP reduction.
Main Methods:
- Administration of SQ 27986 (DP receptor agonist) and BW A868C (DP receptor antagonist) in cats and rabbits.
- Assessment of intraocular pressure, conjunctival microvascular permeability, and goblet cell population.
- Blocking studies using BW A868C to confirm DP receptor involvement in PGD2's hypotensive effect.
Main Results:
- SQ 27986 effectively lowered IOP in cats and rabbits without causing ocular surface pathology.
- BW A868C blocked the ocular hypotensive effect of PGD2 in rabbits, confirming DP receptor mediation.
- PGD2-induced conjunctival microvascular permeability was inhibited by BW A868C, suggesting complex DP receptor signaling.
Conclusions:
- Selective DP receptor agonists are promising for IOP reduction with minimal ocular surface toxicity.
- The DP receptor is critical for PGD2's IOP-lowering effects in rabbits.
- Unexpected findings regarding PGD2's vascular effects suggest potential DP receptor subtypes or signaling pathways.