A new model of experimental subretinal neovascularization in the rabbit
Guanting Qiu1, Jay M Stewart, Srinivas Sadda
1Doheny Retina Institute, Keck School of Medicine, University of Southern California, 1450 San Pablo Street DEI 3622, Los Angeles, CA 90033-3699, USA. gqiu@doheny.org
Abstract:
Existing animal models of choroidal neovascularization (CNV) present several problems: they are hard to reproduce, they are inefficient, and the CNV created is not sustainable. The purpose of this study is to develop a highly efficient, reliable, sustainable rabbit model of CNV to facilitate the study of anti-angiogenic and anti-proliferative therapies for ocular diseases. Twenty-two pigmented rabbits were used in this study. Eleven rabbits received subretinal injections of either 10 microl of Matrigel with 500 ng of vascular endothelial growth factor (VEGF) or 20 microl of Matrigel with 750 ng of VEGF; eight rabbits received subretinal injections of either 10 or 20 microl of Matrigel only; three rabbits used as controls received subretinal injections of 20 microl phosphate-buffered saline (PBS) alone. Fundus photography, fluorescein angiography, optical coherence tomography, and histologic examinations were performed 1, 2, 4, and 9 weeks after injection. All experimental eyes showed angiographic leakage within this localized area 1 week after injection. The amount of leakage usually increased at weeks 2 and 4 and, in most cases, persisted at week 9. Control eyes demonstrated no leakage at any time point. Optical coherence tomography of treated eyes showed subretinal fluid and the presence of a lesion, possibly vascular or fibrotic, at the site of the leakage. Histologic analysis confirmed the presence of new subretinal blood vessels in the areas of Matrigel deposit. In conclusion, this novel method provides a highly reproducible, reliable, and sustainable rabbit model of experimental choroidal neovascularization. Such a model may prove useful for screening new anti-angiogenic therapies in a larger animal eye.
Insights
Researchers developed a new rabbit model for choroidal neovascularization (CNV), overcoming issues with existing methods. This reliable and sustainable model aids in studying anti-angiogenic therapies for eye diseases.
Area of Science:
- Ophthalmology
- Vascular Biology
- Animal Models
Background:
- Current animal models for choroidal neovascularization (CNV) lack reproducibility, efficiency, and sustainability.
- There is a need for a robust model to study therapies for ocular diseases characterized by CNV.
Purpose of the Study:
- To develop a highly efficient, reliable, and sustainable rabbit model of experimental choroidal neovascularization (CNV).
- To facilitate the study of anti-angiogenic and anti-proliferative therapies for ocular diseases.
Main Methods:
- Twenty-two pigmented rabbits were utilized.
- Subretinal injections of Matrigel with vascular endothelial growth factor (VEGF) were administered to experimental groups.
- Control groups received Matrigel only or phosphate-buffered saline (PBS).
- Ophthalmic imaging (fundus photography, fluorescein angiography, OCT) and histology were performed at multiple time points (1, 2, 4, 9 weeks).
Main Results:
- All treated eyes exhibited angiographic leakage by week 1, which increased and persisted up to 9 weeks.
- Optical coherence tomography revealed subretinal fluid and lesions at leakage sites.
- Histologic analysis confirmed the presence of new subretinal blood vessels.
- Control eyes showed no leakage.
Conclusions:
- A novel, reproducible, reliable, and sustainable rabbit model for experimental choroidal neovascularization (CNV) has been established.
- This model is suitable for screening novel anti-angiogenic therapies for ocular conditions.


