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Editors Selection IGR 11-2

Medical Treatment: IOP reduction by EP2 & EP4 agonists

Comment by Achim Krauss on:

23942 Effects of prostanoid EP agonists on mouse intraocular pressure, Saeki T; Ota T; Aihara M et al., Investigative Ophthalmology and Visual Science, 2009; 50: 2201-2208

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Prostaglandin F2α analogs are the most effective ocular hypotensive agents currently available for the treatment of glaucoma and ocular hypertension. More recently, a different class of prostaglandins has received attention ‐ PGE2 analogs that specifically target one of the four E-type prostaglandin receptors (EP1, EP2, EP3, EP4). By employing agonists selective for each of the EP receptor subtypes Saeki et al. (831) demonstrate that EP2 and EP4 agonists, but not EP1 and EP3 agonists, reduce IOP in mice.

EP2 and EP4 agonists, but not EP1 and EP3 agonists, reduce IOP in mice

The activity of the EP2 agonist was abrogated in EP2-knock-out mice, but unaffected in EP1-KO and EP3-KO mice, thus providing clear evidence of the involvement of the EP2 receptor in IOP regulation. Due to high post-natal mortality, EP4-KO mice were not available. Given its pharmacological profile coupled with the finding that the EP4 agonist was fully effective in EP1-3-KO animals provides evidence of the involvement of EP4 receptors in IOP regulation. The evidence generated in this mouse model is in good agreement with reports on EP2 (Woodward et al., 1995; Nilsson et al., 2006) and EP4 mimetics (Woodward et al., 2009; Prasanna et al., 2009) in higher species. Both PGE2 analogs lowered IOP in FP-KO mice compared to wild-type mice, suggesting that their

The mouse model offers the ability to further substantiate data obtained with pharmacological tools through the use of knock-out animals

ocular hypotensive activity is not mediated through the receptor sensitive to PGF2α analogs. Neither EP2 nor EP4 agonist modulated pressure-dependent outflow. No other aqueous humor dynamics parameters were investigated. The lack of effect on conventional outflow is in agreement with higher species for the EP2 agonist (Nilsson et al., 2006), but not for the EP4 agonist which lowers IOP via the conventional route in non-human primates (Woodward et al., 2009). In summary, this study further supports the concept that prostaglandin EP2 and EP4 receptors are involved in IOP regulation. The mouse model provides a powerful tool since it offers the ability to further substantiate data obtained with pharmacological tools through the use of knock-out animals.

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