Published Online
on June 23, 2003

A more recent version of this article appeared on July 15, 2003

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Basic Science Reports

Cyclooxygenase-2 in Human and Experimental Ischemic Proliferative Retinopathy

F. Sennlaub, MD, PhD; F. Valamanesh, MSc; A. Vazquez-Tello, PhD; A. M. El-Asrar, MD, PhD; D. Checchin, MSc; S. Brault, MSc; F. Gobeil, PhD; M. H. Beauchamp, MSc; B. Mwaikambo, BSc; Y. Courtois, PhD; K. Geboes, MD, PhD; D. R. Varma, MD, PhD; P. Lachapelle, PhD; H. Ong, PhD; F. Behar-Cohen, MD, PhD S. Chemtob, MD, PhD

From the Departments of Pediatrics, Ophthalmology, and Pharmacology, Research Center of Hôpital Sainte-Justine (F.S., A.V.-T., D.C., S.B., F.G., M.H.B., B.M., S.C.); Departments of Pharmacology (D.R.V., B.M.) and Ophthalmology (P.L.), McGill University; and Faculty of Pharmacy, Université de Montréal (H.O.), Montreal, Québec, Canada, and Développement, Vieillissement et Pathologie de la Rétine, Institut National de la Santé et de la Recherche Médicale U450, Paris, France (F.V., Y.C., F.B.C.); Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia (A.M.E.-A.); and Department of Pathology, University Hospitals Leuven, Belgium (K.G.).

Correspondence to Florian Sennlaub, MD, PhD, Department of Pediatrics, Centre de Recherche, Hôpital Sainte-Justine, 3175, chemin de la Côte-Sainte-Catherine, Montréal, Québec, Canada H3T 1C5. E-mail fsennlaub{at}justine.umontreal.ca

Background— Intravitreal neovascular diseases, as in ischemic retinopathies, are a major cause of blindness. Because inflammatory mechanisms influence vitreal neovascularization and cyclooxygenase (COX)–2 promotes tumor angiogenesis, we investigated the role of COX-2 in ischemic proliferative retinopathy.

Methods and Results— We describe here that COX-2 is induced in retinal astrocytes in human diabetic retinopathy, in the murine and rat model of ischemic proliferative retinopathy in vivo, and in hypoxic astrocytes in vitro. Specific COX-2 but not COX-1 inhibitors prevented intravitreal neovascularization, whereas prostaglandin E₂, mainly via its prostaglandin E receptor 3 (EP₃), exacerbated neovascularization. COX-2 inhibition induced an upregulation of thrombospondin-1 and its CD36 receptor, consistent with the observed antiangiogenic effects of COX-2 inhibition; EP₃ stimulation reversed effects of COX-2 inhibitors on thrombospondin-1 and CD36.

Conclusion— These findings point to an important role for COX-2 in ischemic proliferative retinopathy, as in diabetes.

Key Words: prostaglandins • diabetes mellitus • ischemia • vasculature

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