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Sara R. Savage, Rong Yang, Susan E. Yanni, John S. Penn; The PGF2 FP Receptor Mediates Retinal Angiogenic Cell Behaviors In Vitro. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4860.
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Prostanoids contribute to the pathological angiogenesis that characterizes many diseases, including neovascular eye conditions. We have previously shown that the prostanoid PGF2 is increased in Müller cells and retinal microvascular endothelial cells exposed to disease-relevant stimuli. PGF2 is thought to affect the angiogenic process by binding to its high-affinity receptor, FP. The purpose of the present study was to investigate the role of FP receptor activation in VEGF production by Müller cells and in VEGF-induced proliferation and tube formation by retinal microvascular endothelial cells.
Müller cells derived from COX-2 null mice were treated with increasing concentrations (0.1-10 µM) of the FP agonist Latanoprost. VEGF message and protein were assessed by RT-PCR and ELISA, respectively. Human retinal microvascular endothelial cells (HRMEC) were treated with increasing concentrations (0.1-10 µM) of Latanoprost, and cell proliferation was assessed by BrdU incorporation. HRMEC were treated with increasing concentrations of the FP antagonist AL-8810 (0.1-10 µM), and tubulogenesis was assessed in Matrigel assays.
COX-2 null mouse Müller cells treated with 10 µM Latanoprost demonstrated a 1.3-fold increase in VEGF mRNA expression. Similarly, treatment with 10 µM Latanoprost led to a two-fold increase in the level of VEGF protein secreted by Müller cells (p < 0.03). Increasing concentrations of Latanoprost led to a dose dependent increase in HRMEC proliferation (by approximately 180% at a 10 µM dose). HRMEC treated with 10 µM AL-8810 demonstrated a 50% reduction in tube formation.
Preliminary investigation has demonstrated that FP activation or inhibition influences the behaviors of two retinal cell types that are known to play critical roles in the pathological ocular angiogenesis characteristic of retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration. These studies suggest that the FP receptor may be a rational therapeutic target in neovascular eye disease.
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