Quantitative Image Analysis of Laser-induced Choroidal Neovascularization in Rat

Edelman, J.; Castro, Marisol R.

doi:10.1006/exer.2000.0907

Cited by 124 publications

(100 citation statements)

References 26 publications

(39 reference statements)

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“…After 2 weeks, the mice were anesthetized and perfused with 1 ml of PBS containing 50 mg/ml of fluoresceinlabeled dextran (2 Â 10 6 average mw, Sigma, St Louis, MO, USA) as previously described, 31 and the area of choroidal neovascularization at Bruch's membrane rupture sites was measured on choroidal flat mounts by image analysis. 32 Eyes were removed and fixed for 1 h in 10% phosphate-buffered formalin. The cornea and lens were removed and the entire retina was carefully dissected from the eyecup.…”

Section: Mice With Oxygen-induced Ischemic Retinopathymentioning

confidence: 99%

Angiopoietin 1 inhibits ocular neovascularization and breakdown of the blood–retinal barrier

et al. 2004

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Section: Mice With Oxygen-induced Ischemic Retinopathymentioning

confidence: 99%

Angiopoietin 1 inhibits ocular neovascularization and breakdown of the blood–retinal barrier

et al. 2004

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“…In those eyes, the retina was removed and CNV quantified by Neurolucida analysis of whole mount preparations (Figs 4-6). It could be that AG013764 or AG013711 reduced the amount of AAV-VEGF induced CNV, or reduced the permeability of CNV for dextran, or both (Edelman and Castro 2000;Ferris 2004). In laser induced CNV, high molecular weight fluorescein labeled dextran (2×10 6 molecular weight) is thought to be confined within the neo-vascular blood vessels (Edelman and Castro 2000).…”

Section: Discussionmentioning

confidence: 99%

“…It could be that AG013764 or AG013711 reduced the amount of AAV-VEGF induced CNV, or reduced the permeability of CNV for dextran, or both (Edelman and Castro 2000;Ferris 2004). In laser induced CNV, high molecular weight fluorescein labeled dextran (2×10 6 molecular weight) is thought to be confined within the neo-vascular blood vessels (Edelman and Castro 2000). However, overexpression of VEGF may make these blood vessels more permeable to dextran, as evidenced by an area of hyper-fluorescence that has well-demarcated boundaries and a uniform intensity (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…A noteworthy aspect of the present model is that it allows us to generate relatively large areas of CNV (50-100 times the area of a laser-induced CNV; ˜ 0.03 -0.08 mm 2 (Edelman and Castro 2000;Hangai et al, 2001;Mori et al, 2001;Dejneka et al, 2004) ). In the present study, the intervention started six weeks after the initial injection of AAV-VEGF and at least 1-2 weeks after the development of CNV.…”

Section: Discussionmentioning

confidence: 99%

“…Using a method similar to that previously described (Edelman and Castro 2000), each animal was perfused intracardially with 50 ml PBS to wash out the blood and followed immediately by 20 ml of 10% gelatin and 2.5% FITC-dextran (MW: 2×10 6 Sigma, St. Louis, MO, USA). FITC-dextran perfused rats were kept in the refrigerator at 4°C for two to four hours to solidify the gelatin.…”

Section: Fluorescein Angiography and Fitc-dextran Flat-mount Of Rpe-cmentioning

confidence: 99%

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Receptor tyrosine kinase inhibitors AG013764 and AG013711 reduce choroidal neovascularization in rat eye

Wang

Shi

Niesman

et al. 2007

Experimental Eye Research

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Age-related macular degeneration (AMD) is the major cause of blindness for people over 60. In the "wet" form of AMD compounds targeting growth factor signaling pathways such as VEGF have been a major focus for therapeutic interventions. In a previously developed rat model of CNV, we utilized two receptor tyrosine kinase inhibitors (RTKi) to block VEGFR-1, VEGFR-2 and PDGFR signaling following the establishment of CNV. AAV-VEGF 165 was injected into the subretinal space of rats at postnatal days 15-17. Six weeks later, a suspension of RTK inhibitors, AG013764 or AG013711, was injected intraperitoneally (IP, twice daily) or intravitreally (every five days) over a two week period. FITC-dextran whole-mounts of RPE-choroid-sclera were prepared after the animals were sacrificed. CNV area was quantified using Neurolucida to measure the hyperfluorescence on FITC-dextran whole-mounts. Histology and immunohistochemistry were performed as described previously. VEGF expression in control and treated eyes was confirmed by immunohistochemistry and histological sections indicated recovery of retinal morphology and CNV reduction in treated eyes. In the animals IP injected with AG013764 or AG013711 the mean CNV level was reduced by 25 to 33% compared to control, but this effect did not achieve statistical significance. Intravitreal injections of AG013764 or AG013711 reduced the level of CNV by approximately 60% compared to control (p< 0.005 or p< 0.05, respectively). These data show that two RTK inhibitors, AG013764 or AG013711, delivered intravitreally, significantly reduce blood vessel proliferation in this AAV-VEGF 165 model of CNV.

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Inhibition of Choroidal Neovascularization by a Peptide Inhibitor ofthe Urokinase Plasminogen Activator and Receptor System in a Mouse Model

Das

Boyd²,

Jones³

et al. 2004

Arch Ophthalmol

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To determine the role played by the urokinase plasminogen activator (uPA) and urokinase plasminogen activator receptor (uPAR) system in choroidal neovascularization (CNV) and whether inhibition of this system can suppress the extent of CNV in an animal model. Methods: Choroidal neovascularization was induced in mice by laser photocoagulation using the slitlamp delivery system. Reverse transcriptase-polymerase chain reaction and immunocytochemical analysis were performed on the retina choroids of these animals to examine the expression of uPAR. For 2 weeks following laser treatment, animals were injected intraperitoneally with a novel peptide inhibitor of the uPA-uPAR system (100 mg/kg twice a day every day, every other day, and once a week). Control laser-treated animals receive an intraperitoneal injection of phosphate-buffered saline every day. Following treatment, animals were perfused with fluoresceinlabeled dextran, eyes were removed, and the areas of new vessels were examined in the retina-choroid whole mounts by fluorescence microscopy and quantitated using image analysis software. Results: In this study, uPAR was found to be upregulated in the choroidal tissues of mice with laserinduced CNV. The uPAR was localized to the endothelial cells of the fibrovascular tissue within the CNV complex. Systemic administration of the peptide inhibitor of the uPA-uPAR system resulted in a significant reduction of CNV (up to 94%). The response was found to be frequency-of-dose dependent. No toxic effects or tissue destruction was noted following the peptide treatment. Conclusions: Our results strongly suggest that upregulation of the uPA-uPAR system is an important step during CNV, and significant inhibition of CNV was seen when cell surface-associated uPA-uPAR activity was prevented with the peptide inhibitor.

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Quantitative Image Analysis of Laser-induced Choroidal Neovascularization in Rat

Cited by 124 publications

References 26 publications

Angiopoietin 1 inhibits ocular neovascularization and breakdown of the blood–retinal barrier

Angiopoietin 1 inhibits ocular neovascularization and breakdown of the blood–retinal barrier

Receptor tyrosine kinase inhibitors AG013764 and AG013711 reduce choroidal neovascularization in rat eye

Inhibition of Choroidal Neovascularization by a Peptide Inhibitor ofthe Urokinase Plasminogen Activator and Receptor System in a Mouse Model

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