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Editors Selection IGR 11-3

Basic Research: EP2 - receptor and agonist for treating glaucoma dysfunction

Comment by Makoto Aihara on:

24080 Expression of prostaglandin PGE2 receptors under conditions of aging and stress and the protective effect of the EP2 agonist butaprost on retinal ischemia, Osborne NN; Li GY; Ji D et al., Investigative Ophthalmology and Visual Science, 2009; 50: 3238-3248

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Four different types of EP receptors are present in the retina, functioning through different intracellular signaling pathways. So far, EP receptors may have been recognized as detrimental receptors to induce ocular diseases because general agonist PGE2 induces inflammation in total by the stimulation of EP1-4 receptors. In this paper by Osborne et al., (1238) the distribution and dimerization of each EP receptor were investigated well in detail by aging and stress. These data was well assessed by immunohistochemisty and western blot analysis. One of my concerns is whether the antibody sufficiently detects homodimer or heterodimer and monomer of EP receptors both in the tissue and in the western blotting. It has not been clarified whether the dimers are homo or hetero. The authors revealed the change of dimer/monomer ratio by ischemic stress, but the effect of butaprost on EP2 receptor profile in the normal and ischemic stress was not assessed. Moreover, it has not been discussed what this dimerization itself means. The binding of butaprost to EP2 may change the receptor dimerization of EP receptors. Also, such seven trans-membrane type receptors easily consist heterodimers. Thus, the other receptors may contribute to show the neuroprotective effect. In future, these receptor profile and neuroprotective effect by butaprost should be assessed in RGC culture, because in this study, the change of receptors and the physiological function and protein expression of the retina was evaluated using the whole retina.

EP2 receptor and its agonist may have a strong potential to treat ocular dysfunction, especially glaucoma

We have found that EP receptors may elicit various cellular response in each cell. It has been recently reported that EP2 and EP4 agonists reduce intraocular pressure successfully in animal models. Moreover, including this paper, EP2 agonist and EP4 agonist protected the ischemia‐induced retinal dysfunction. The presence of EP2 receptor in RGC, neuroprotective effect on ischemia by EP2 agonist, and IOP reduction through EP2 receptor suggest that EP2 receptor and its agonist may have a strong potential to treat ocular dysfunction, especially glaucoma.

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