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Updated: Aug 9, 2026
Limbal Approach-Subretinal Injection of Viral Vectors for Gene Therapy in Mice Retinal Pigment Epithelium
Published on: August 7, 2015
Potential long-term inhibition of ocular neovascularisation by recombinant adeno-associated virus-mediated secretion
Y K Y Lai1, W Y Shen, M Brankov
1Department of Molecular Ophthalmology, Lions Eye Institute, Nedlands, Western Australia, Australia.
Abstract:
Neovascularisation (NV) within the eye often results in visual loss. Vascular endothelial growth factor (VEGF) has been implicated in the development of ocular NV. Previous studies have shown that VEGF antagonists successfully suppressed retinal and choroidal NV in animal models. However, the systemic approach and transient nature of the delivery systems used in these studies hinder therapeutic application. To achieve stable and localised ocular anti-angiogenic therapy, we explored the use of recombinant adeno-associated virus (rAAV)-mediated secretion gene therapy (SGT). In this study, we generated a rAAV vector encoding soluble VEGF receptor 1, sFlt-1 (AAV-CMV.sflt) and determined its ability to inhibit cautery-induced corneal NV and laser-induced choroidal NV. Delivery of AAV-CMV.sflt into the anterior chamber resulted in transgene expression in the iris pigment epithelium and corneal endothelium, which reduced the development of corneal NV in the stroma of cauterised rats by 36% compared with cauterised control groups (P = 0.009). Subretinal delivery of AAV-CMV.sflt near the equator of the eye also suppressed choroidal NV at the laser lesions around the optic nerve by 19% (P = 0.002), indicating that there was diffusion of the secreted anti-angiogenic protein across the retina. Both results suggest that the long-term suppression of ocular NV is possible through the use of stable rAAV-mediated SGT.
Insights
Recombinant adeno-associated virus (rAAV)-mediated gene therapy effectively suppressed ocular neovascularization (NV). This stable, localized approach offers a promising new treatment for vision loss caused by NV.
Area of Science:
- Ophthalmology
- Gene Therapy
- Angiogenesis Research
Background:
- Ocular neovascularization (NV) is a major cause of vision loss.
- Vascular endothelial growth factor (VEGF) plays a key role in ocular NV development.
- Previous anti-VEGF therapies had limitations due to systemic delivery and transient effects.
Purpose of the Study:
- To investigate the potential of recombinant adeno-associated virus (rAAV)-mediated secretion gene therapy (SGT) for stable, localized ocular anti-angiogenic treatment.
- To evaluate the efficacy of a rAAV vector encoding soluble VEGF receptor 1 (sFlt-1) in inhibiting corneal and choroidal NV.
Main Methods:
- Generation of a rAAV vector (AAV-CMV.sflt) encoding sFlt-1.
- Delivery of AAV-CMV.sflt into the anterior chamber to assess corneal NV inhibition in rats.
- Subretinal delivery of AAV-CMV.sflt to evaluate choroidal NV suppression in laser-induced models.
Main Results:
- Anterior chamber delivery reduced corneal NV by 36% (P = 0.009).
- Subretinal delivery suppressed choroidal NV by 19% (P = 0.002), demonstrating retinal diffusion.
- Transgene expression was confirmed in ocular tissues following vector delivery.
Conclusions:
- Stable, rAAV-mediated SGT is a viable strategy for long-term suppression of ocular NV.
- This approach overcomes limitations of previous anti-VEGF therapies, offering localized and sustained therapeutic effects.
- The study highlights the potential of gene therapy for treating vision-threatening neovascular eye diseases.
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