TY - JOUR
T1 - Trans-scleral delivery of polyamine analogs for ocular neovascularization
AU - Lima e Silva, Raquel
AU - Kachi, Shu
AU - Akiyama, Hideo
AU - JiKui Shen, Shen
AU - Hatara, Maria Christina
AU - Aslam, Sadia
AU - Gong, Yuan Yuan
AU - Khu, Naw Htee
AU - Lauer, Thomas W.
AU - Hackett, Sean F.
AU - Marton, Laurence J.
AU - Campochiaro, Peter A.
N1 - Funding Information:
Supported by the Foundation Fighting Blindness, the Macula Vision Foundation, and a grant from Dr. and Mrs. William Lake.
Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2006/11
Y1 - 2006/11
N2 - 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 μg 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.
AB - 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 μg 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.
KW - age-related macular degeneration
KW - angiogenesis
KW - choroidal neovascularization
KW - endothelial cells
KW - polyamines
KW - proliferative retinopathies
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U2 - 10.1016/j.exer.2006.07.003
DO - 10.1016/j.exer.2006.07.003
M3 - Article
C2 - 16950258
AN - SCOPUS:33748705734
SN - 0014-4835
VL - 83
SP - 1260
EP - 1267
JO - Experimental eye research
JF - Experimental eye research
IS - 5
ER -