This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (15)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Ophthalmology, Other  • Alert me on articles by topic

Michael J. Tolentino, MD; Deeba Husain, MD; Panagiotis Theodosiadis, MD; Evangelos S. Gragoudas, MD; Edward Connolly, BS; Jeanne Kahn, BS; Jeffrey Cleland, BS; Anthony P. Adamis, MD; Andrew Cuthbertson, MD; Joan W Miller, MD

Arch Ophthalmol. 2000;118:78-84.

Objective  To determine if anti–vascular endothelial growth factor antibody and a range of dextrans with varying diffusion radii and molecular weights are permeable through experimental choroidal neovascularization (CNV).

Methods  Choroidal neovascularization was induced in 10 cynomolgus monkey retinas by means of argon laser injury. Digital fundus fluorescein angiograms were performed with fluorescein sodium, fluoresceinated IgG antibodies (anti–vascular endothelial growth factor and a control antibody), and fluoresceinated dextrans with molecular weights of 4, 20, 40, 70 and 150 kd. The 40- and 70-kd dextrans straddle the effective diffusion radius of IgG. For each reagent, early and late angiograms were performed in a standardized fashion, with follow-up images obtained to monitor residual fluorescence.

Results  Perfusion of retinal vessels and choroidal vasculature was seen with all reagents. Fluorescein and 4- and 20-kd dextran leaked rapidly from the CNV within the first minute. Angiography with the use of 40-kd dextran and fluoresceinated antibody, either anti–vascular endothelial growth factor or control IgG, showed fluorescence within the CNV that increased during the first 1 to 5 hours, with mild leakage from the CNV. By 24 hours, fluorescence in the CNV was minimal, although in some cases persistent fluorescence in the surrounding tissue was evident up to 2 weeks. The 70-kd dextran showed fluorescence within the CNV and leakage in 1 of 3 eyes. The 150-kd dextran showed fluorescence within the CNV but did not demonstrate leakage.

Conclusions  Fluoresceinated antibodies and dextran with smaller effective diffusion radii showed CNV perfusion and leakage. Dextrans with larger effective diffusion radii (70 kd and 150 kd) perfused into CNV but did not show leakage consistently.

Clinical Relevance  Determining the permeablity of antibodies and molecules of similar size through CNV can help ascertain the feasibility of using intravenously administered antibodies against angiogenic growth factors as a future treatment for choroidal neovascularization.

From the Retina Service, Massachusetts Eye and Ear Infirmary (Drs Tolentino, Theodosiadis, Husain, Gragoudas, Adamis, and Miller and Mr Connolly), and Surgical Research Laboratories, Children's Hospital (Dr Adamis), Harvard Medical School, Boston, Mass; and Genentech Inc, South San Francisco, Calif (Ms Kahn, Mr Cleland, and Dr Cuthbertson).

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Hepatocyte Growth Factor Induces Retinal Vascular Permeability via MAP-Kinase and PI-3 Kinase without Altering Retinal Hemodynamics.
Clermont et al.
IOVS 2006;47:2701-2708.
ABSTRACT | FULL TEXT  

Single Periocular Injection of Celecoxib-PLGA Microparticles Inhibits Diabetes-Induced Elevations in Retinal PGE2, VEGF, and Vascular Leakage.
Amrite et al.
IOVS 2006;47:1149-1160.
ABSTRACT | FULL TEXT  

Anastomotic Vessels Remain Viable after Photodynamic Therapy in Primate Models of Choroidal Neovascularization
Criswell et al.
IOVS 2005;46:2168-2174.
ABSTRACT | FULL TEXT  

Selective Photodynamic Therapy by Targeted Verteporfin Delivery to Experimental Choroidal Neovascularization Mediated by a Homing Peptide to Vascular Endothelial Growth Factor Receptor-2
Renno et al.
Arch Ophthalmol 2004;122:1002-1011.
ABSTRACT | FULL TEXT  

The Squirrel Monkey: Characterization of a New-World Primate Model of Experimental Choroidal Neovascularization and Comparison with the Macaque
Criswell et al.
IOVS 2004;45:625-634.
ABSTRACT | FULL TEXT  

Investigation of Laser-Induced Choroidal Neovascularization in the Rat
Semkova et al.
IOVS 2003;44:5349-5354.
ABSTRACT | FULL TEXT  

Targeting of Interferon to Choroidal Neovascularization by Use of Dextran and Metal Coordination
Yasukawa et al.
IOVS 2002;43:842-848.
ABSTRACT | FULL TEXT  

Monoclonal Antibody-Mediated Drug Targeting to Choroidal Neovascularization in the Rat
Kamizuru et al.
IOVS 2001;42:2664-2672.
ABSTRACT | FULL TEXT