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Regression of ocular neovascularization in response to increased expression of pigment epithelium-derived factor
Keisuke Mori1, Peter Gehlbach, Akira Ando
1Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-9277, USA.
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 (PEDF) 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.
Insights
Gene therapy using pigment epithelium-derived factor (PEDF) successfully regressed established ocular neovascularization in mouse models. This approach promotes apoptosis within neovascular lesions, offering a potential new treatment for eye conditions.
Area of Science:
- Ophthalmology
- Gene Therapy
- Molecular Biology
Background:
- Existing treatments for ocular neovascularization are effective before stimulus onset but fail to regress established conditions.
- Ocular neovascularization, driven by factors like vascular endothelial growth factor (VEGF), poses a significant threat to vision.
Purpose of the Study:
- To investigate the efficacy of adenoviral-vectored pigment epithelium-derived factor (PEDF) gene transfer in regressing established ocular neovascularization.
- To evaluate PEDF gene therapy in transgenic mouse models with VEGF-induced neovascularization and laser-induced choroidal neovascularization.
Main Methods:
- Adenoviral vector carrying a PEDF expression construct (AdPEDF.11) or a control vector (AdNull.11) was administered via intravitreous or subretinal injection.
- Neovascularization was quantified using image analysis before and after treatment in rho/VEGF mice and a choroidal neovascularization model.
Main Results:
- AdPEDF.11 injection led to significant regression of ocular neovascularization in both mouse models.
- TUNEL staining confirmed apoptosis within neovascular lesions in eyes treated with AdPEDF.11, indicating cell death.
Conclusions:
- Pigment epithelium-derived factor (PEDF) gene transfer effectively induces regression of established ocular neovascularization.
- The mechanism involves promoting apoptosis of cells within neovascular lesions, suggesting a novel therapeutic strategy for ocular neovascular diseases.