Regression of ocular neovascularization in response to increased expression of pigment epithelium-derived factor

Keisuke Mori, Peter Gehlbach, Akira Ando, Duncan McVey, Lisa Wei, Peter A Campochiaro

Research output: Contribution to journalArticle

Abstract

PURPOSE. Several pharmacologic treatments have been shown to reduce ocular neovascularization when administered before the onset of angiogenic stimuli, but none have been shown to cause regression of already established ocular neovascularization. In this study, the authors tested the effect of adenoviral vectored pigment epithelium-derived factor (PEDT) gene transfer on established neovascularization in transgenic mice with expression of vascular endothelial growth factor (VEGF) in photoreceptors (rho/VEGF mice) and in a model of choroidal neovascularization. METHODS. Two weeks after the onset of VEGF transgene expression in rho/VEGF mice or 2 weeks after laser-induced rupture of Bruch's membrane in wild-type mice, subgroups of mice were killed, and the baseline amount of neovascularization was measured by image analysis. The remainder of the mice received an intravitreous or subretinal injection of adenoviral vector containing a PEDF expression construct (AdPEDF. 11) or control vector (AdNull.11). RESULTS. Seven days after injection in rho/VEGF mice or 10 days after injection in the choroidal neovascularization model, the amount of neovascularization in AdPEDF. 11-injected eyes was significantly less than the baseline level, indicating that regression of neovascularization had occurred. There was TUNEL staining within choroidal neovascular lesions in eyes injected with AdPEDF. 11. Eyes given a subretinal injection of AdNull. 11 had TUNEL-positive cells in the retina, but none within areas of choroidal neovascularization. CONCLUSIONS. These data indicate that increased expression of PEDF causes regression of ocular neovascularization by promoting apoptosis of cells within neovascular lesions and possibly represents a new treatment paradigm for patients with established ocular neovascularization.

Original languageEnglish (US)
Pages (from-to)2428-2434
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume43
Issue number7
StatePublished - 2002

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Vascular Endothelial Growth Factor A
Choroidal Neovascularization
Injections
In Situ Nick-End Labeling
Bruch Membrane
pigment epithelium-derived factor
Transgenes
Transgenic Mice
Retina
Rupture
Lasers
Apoptosis
Staining and Labeling
Therapeutics
Genes

ASJC Scopus subject areas

  • Ophthalmology

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Regression of ocular neovascularization in response to increased expression of pigment epithelium-derived factor. / Mori, Keisuke; Gehlbach, Peter; Ando, Akira; McVey, Duncan; Wei, Lisa; Campochiaro, Peter A.

In: Investigative Ophthalmology and Visual Science, Vol. 43, No. 7, 2002, p. 2428-2434.

Research output: Contribution to journalArticle

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N2 - PURPOSE. Several pharmacologic treatments have been shown to reduce ocular neovascularization when administered before the onset of angiogenic stimuli, but none have been shown to cause regression of already established ocular neovascularization. In this study, the authors tested the effect of adenoviral vectored pigment epithelium-derived factor (PEDT) gene transfer on established neovascularization in transgenic mice with expression of vascular endothelial growth factor (VEGF) in photoreceptors (rho/VEGF mice) and in a model of choroidal neovascularization. METHODS. Two weeks after the onset of VEGF transgene expression in rho/VEGF mice or 2 weeks after laser-induced rupture of Bruch's membrane in wild-type mice, subgroups of mice were killed, and the baseline amount of neovascularization was measured by image analysis. The remainder of the mice received an intravitreous or subretinal injection of adenoviral vector containing a PEDF expression construct (AdPEDF. 11) or control vector (AdNull.11). RESULTS. Seven days after injection in rho/VEGF mice or 10 days after injection in the choroidal neovascularization model, the amount of neovascularization in AdPEDF. 11-injected eyes was significantly less than the baseline level, indicating that regression of neovascularization had occurred. There was TUNEL staining within choroidal neovascular lesions in eyes injected with AdPEDF. 11. Eyes given a subretinal injection of AdNull. 11 had TUNEL-positive cells in the retina, but none within areas of choroidal neovascularization. CONCLUSIONS. These data indicate that increased expression of PEDF causes regression of ocular neovascularization by promoting apoptosis of cells within neovascular lesions and possibly represents a new treatment paradigm for patients with established ocular neovascularization.

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