Attenuation of Laser-Induced Choroidal Neovascularization by Blockade of Prostaglandin D2 Receptor 2.

PURPOSE: The purpose of this study was to investigate the impact of prostaglandin D2 (PGD2) receptor 2 (DP2) on choroidal neovascularization (CNV) formation in mice.

METHODS: Using a laser-induced CNV model, the CNV size of wild-type (WT) mice treated with DP2 antagonist (CAY10471 or OC000459) was compared with that of untreated mice. Vascular endothelial growth factor (VEGF) and MCP-1 levels were also compared between the two groups. Similar experiments were performed comparing DP2 knockout (DP2KO) mice with WT mice (8 and 56 weeks old). The number of infiltrating macrophages to laser spots was also compared between the WT and DP2KO mice. We administered a DP2 antagonist to 15-methyl PGD2 (a DP2 agonist)-stimulated ARPE-19 cells and measured VEGF secretion by enzyme-linked immunosorbent assay. Tube formation assay was performed on human umbilical vein endothelial cells with or without a DP2 antagonist.

RESULTS: CNV sizes were significantly smaller in mice treated with CAY10471 or OC000459 than in those treated with vehicle. Similarly, the CNV size of DP2KO mice was significantly smaller than that of WT mice. The number of macrophages at laser spots in DP2KO mice was significantly lower than that in WT mice. The VEGF concentration of lasered DP2KO mice's eyes was significantly lower than that of lasered WT mice' eyes. DP2 antagonist treatment suppressed VEGF secretion in ARPE-19 cells under 15-methyl PGD2 stimulation. The tube formation assay suggested that lumen formation was inhibited by a DP2 antagonist.

CONCLUSIONS: DP2 blockade attenuated choroidal neovascularization.

TRANSLATIONAL RELEVANCE: Drugs targeting DP2 are potentially a novel treatment for age-related macular degeneration.