Trans-scleral delivery of polyamine analogs for ocular neovascularization.
Periocular injections of the polyamine analog CGC-11144 three times a week causes regression of choroidal neovascularization. This regimen was selected to maximize chances of success for proof of concept, but is not ideal for clinical application. In this study we explored other regimens for periocular delivery of CGC-11144, and 2 other polyamine analogs, CGC-11047 and CGC-11093. A single periocular injection of 200 microg of CGC-11144, 2 mg of CGC-11047, or 1.5 mg of CGC-11093 caused significant suppression and regression of laser-induced choroidal neovascularization. An injection of 2 mg of CGC-11047 or 1.5 mg of CGC-11093 one or two weeks before, but not 3 weeks before, rupture of Bruch's membrane also caused significant suppression. Periocular injection of polyamine analogs also caused strong inhibition of retinal or subretinal neovascularization in mice with oxygen-induced ischemic retinopathy or Rhodopsin promoter/VEGF transgenic mice, respectively. These data suggest that periocular injection of one of 3 different polyamine analogs inhibits retinal or choroidal neovascularization and a single injection provides inhibitory activity for at least 2 to 3 weeks, which could provide the basis for a feasible treatment regimen for clinical trials.
Lima e Silva
Raquel
R
The Departments of Ophthalmology and Neuroscience, The Johns Hopkins University School of Medicine, Maumenee 719, 600 N. Wolfe Street, Baltimore, MD 21287-9277, USA.
Kachi
Shu
S
Akiyama
Hideo
H
Shen
JiKui
J
Hatara
Maria Christina
MC
Aslam
Sadia
S
Gong
Yuan Yuan
YY
Khu
Naw Htee
NH
Lauer
Thomas W
TW
Hackett
Sean F
SF
Marton
Laurence J
LJ
Campochiaro
Peter A
PA
D000818:Animals; D015317:Biogenic Polyamines / Q000008:administration & dosage*; D016570:Bruch Membrane / Q000293:injuries; D020256:Choroidal Neovascularization / Q000188:drug therapy*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D007274:Injections, Intraperitoneal; D007511:Ischemia / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009883:Ophthalmic Solutions / Q000008:administration & dosage*; D010100:Oxygen; D020419:Photoreceptor Cells, Vertebrate / Q000737:chemistry; D011073:Polyamines / Q000494:pharmacology; D015861:Retinal Neovascularization / Q000188:drug therapy; D012171:Retinal Vessels / Q000187:drug effects; D012421:Rupture; D013997:Time Factors; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
D015317:Biogenic Polyamines; C515675:CGC 11047; C515676:CGC 11093; C505025:CGC-11144; D009883:Ophthalmic Solutions; D011073:Polyamines; D042461:Vascular Endothelial Growth Factor A; D010100:Oxygen