Reduced choroidal neovascular membrane formation in cyclooxygenase-2 null mice.
OBJECTIVE
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.
Rezaei
Kasra A
KA
Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
Toma
Hassanain S
HS
Cai
Jiyang
J
Penn
John S
JS
Sternberg
Paul
P
Kim
Stephen J
SJ
D000818:Animals; D002829:Choroid / Q000378:metabolism; D020256:Choroidal Neovascularization / Q000201:enzymology* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000502:physiology*; D004195:Disease Models, Animal; D005451:Fluorescein Angiography; D053583:Interleukin-1beta / Q000378:metabolism*; D017075:Laser Coagulation; D051379:Mice; D008810:Mice, Inbred C57BL; D012160:Retina / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2