Reduced choroidal neovascular membrane formation in cyclooxygenase-2 null mice.

Rezaei KA, Toma HS, Cai J, Penn JS, Sternberg P, Kim SJ
Invest Ophthalmol Vis Sci. 2011 52 (2): 701-7

PMID: 20881304 · PMCID: PMC3053102 · DOI:10.1167/iovs.10-6319

PURPOSE - To assess the degree of laser-induced choroidal neovascular membrane formation in wild-type (WT) and COX-2 null mice and to measure vascular endothelial growth factor (VEGF), interleukin (IL)-1β, and tumor necrosis factor (TNF)-α levels in the retina and choroid.

METHODS - Four laser burns were placed in each eye of WT and COX-2 null mice to induce choroidal neovascularization. Fluorescein angiography (FA) was performed at 14 days, and retinal pigment epithelium-choroid-sclera (choroidal) flat mounts were prepared. The retina and choroid were isolated from WT and COX-2 null mice at 24, 72, and 168 hours after laser photocoagulation and from unlasered eyes and were tested for VEGF, IL-1β, and TNF-α.

RESULTS - COX-2 null mice demonstrated 58% (P = 0.001) and 48% (P = 0.001) reductions in CNV formation on FA and choroidal flat mounts, respectively, compared with WT mice. For unlasered mice, mean VEGF concentrations in the retina and choroid were 1.2 ± 0.42 pg/mg protein for WT but only 0.42 ± 0.2 pg/mg protein for COX-2 null mice (P < 0.05). After laser photocoagulation, WT mice showed significantly greater VEGF and IL-β expression in the retina and choroid by 168 hours (P < 0.05) and 72 hours (P < 0.05), respectively, compared with COX-2 null mice.

CONCLUSIONS - COX-2 null mice exhibited significantly less choroidal neovascular membrane formation associated with reduced expression of VEGF. The results of this study suggest that COX-2 modulates VEGF expression in CNV and implicates a potential therapeutic role for nonsteroidal anti-inflammatory drugs.

MeSH Terms (14)

Animals Choroid Choroidal Neovascularization Cyclooxygenase 2 Disease Models, Animal Fluorescein Angiography Interleukin-1beta Laser Coagulation Mice Mice, Inbred C57BL Retina Retinal Pigment Epithelium Tumor Necrosis Factor-alpha Vascular Endothelial Growth Factor A

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