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Originally published In Press as doi:10.1167/iovs.08-3185 on March 5, 2009
 (Investigative Ophthalmology and Visual Science. 2009;50:3238-3248.)
© 2009 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.08-3185
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Expression of Prostaglandin PGE2 Receptors under Conditions of Aging and Stress and the Protective Effect of the EP2 Agonist Butaprost on Retinal Ischemia

Neville N. Osborne,1 Guang-Yu Li,2 Dan Ji,1 Belmira L. Andrade da Costa,3 Rebecca J. Fawcett,1 Kui Dong Kang,1 and Kay D. Rittenhouse4

1From the Nuffield Laboratory of Ophthalmology, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; 2The Second Hospital of Jilin University, Changchun, China; 3Departmento de Fisiologia e Farmacologia, Cidade Universitária, Recife, PE, Brazil; and 4Pfizer, Translation Medicine in Ophthalmology, San Diego, California.

PURPOSE. To localize different prostaglandin E2 receptors in rat retinas of varying age, deduce how they are affected by acute stress insult, and determine whether the negative effect of ischemia/reperfusion is attenuated by the EP2 agonist butaprost.

METHODS. Ischemia was induced by the elevation of intraocular pressure. Butaprost was injected intravitreally immediately after ischemia. Standard methods were used for recording of electroretinograms (ERGs) and processing of immunohistochemistry. Extracts of whole retinas were analyzed for specific proteins by Western blotting or by RT-PCR for defined mRNAs.

RESULTS. The localization of different EP receptor types is similar in retinas of all aged rats. However, differences exist in the monomer/dimer ratios in retinas of different age. Acute stress insult (48 hours after ischemia) affects the ratio of monomer/dimer of all EP receptor types and increases EP2 and EP3 immunoreactivities in Müller cells of the adult retina. Ischemia and 5 to 7 days of reperfusion to the retina caused the normal ERG and the localization of nNOS and ChAT immunoreactivities to be affected. Certain proteins and mRNAs were lowered in content, whereas other proteins and mRNAs were upregulated. In addition, specific optic nerve proteins were drastically reduced. Most of these changes induced by ischemia/reperfusion were significantly blunted by butaprost.

CONCLUSIONS. All subtypes of EP receptors exist primarily in the inner retina at different ages, but their monomer/dimer ratios vary. Stress affects the monomer/dimer ratio and EP2 and EP3 immunoreactivities in Müller cells. Butaprost injected intravitreally significantly blunts the detrimental influence of ischemia/reperfusion to the retina.






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