title: Ketorolac inhibits choroidal neovascularization by suppression of retinal VEGF.
abstract: We assessed the effect of topical ketorolac on laser-induced choroidal neovascularization (CNV), measured retinal PGE(2) and VEGF levels after laser treatment, and determined the effect of ketorolac on PGE(2) and VEGF production. Six laser burns were placed in eyes of rats which then received topical ketorolac 0.4% or artificial tears four times daily until sacrifice. Fluorescein angiography (FA) was performed at 2 and 3 weeks and retinal pigment epithelium-choroid-sclera flat mounts were prepared. The retina and vitreous were isolated at 1, 3, 5, 7, and 14 days after laser treatment and tested for VEGF and PGE(2). Additional animals were lasered and treated with topical ketorolac or artificial tears and tested at 3 and 7 days for retinal and vitreous VEGF and PGE(2.) Ketorolac reduced CNV on FA by 27% at 2 weeks (P<0.001) and 25% at 3 weeks (P<0.001). Baseline retina and vitreous PGE(2) levels were 29.4 μg/g and 16.5 μg/g respectively, and reached 51.2 μg/g and 26.9 μg/g respectively, 24h after laser treatment (P<0.05). Retinal VEGF level was 781pg/g 24h after laser treatment and reached 931pg/g by 7 days (P<0.01). Ketorolac reduced retinal PGE(2) by 35% at 3 days (P<0.05) and 29% at 7 days (P<0.001) and retinal VEGF by 31% at 3 days (P=0.10) and 19% at 7 days (P<0.001). Topical ketorolac inhibited CNV and suppressed retinal PGE(2) and VEGF production.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, TN, USA. skim30@gmail.com
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kim
authors.forename: Hassanain S
authors.initials: HS
authors.lastname: Toma
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Barnett
authors.forename: John S
authors.initials: JS
authors.lastname: Penn
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D020256:Choroidal Neovascularization / Q000175:diagnosis / Q000378:metabolism / Q000517:prevention & control*; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000378:metabolism; D004195:Disease Models, Animal; D005451:Fluorescein Angiography; D020910:Ketorolac / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D014822:Vitreous Body / Q000187:drug effects / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D015232:Dinoprostone; D020910:Ketorolac