In vivo use of oligonucleotides to inhibit choroidal neovascularisation in the eye
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Updated: Aug 15, 2026
In Vivo Multimodal Imaging and Analysis of Mouse Laser-Induced Choroidal Neovascularization Model
Published on: January 21, 2018
K L Garrett1, W Y Shen, P E Rakoczy
1Department of Molecular Ophthalmology, Lions Eye Institute, Nedlands, Western Australia, Australia.
Background:
We have previously demonstrated the in vivo uptake of oligonucleotides in the rat eye and have continued with experiments to look at the effectiveness of targeted oligonucleotide sequences. Vascular endothelial growth factor (VEGF) is correlated with new blood vessel formation and has been implicated in numerous eye diseases characterised by abnormal blood vessel proliferation. An oligonucleotide targeted to the VEGF sequence was examined for its effect on VEGF production in vitro and the development of choroidal neovascularisation in vivo in the eye.
Methods:
A series of sequences were assessed in an in vitro screening system using retinal pigment epithelial (RPE) cells to demonstrate a reduction in VEGF. A targeted sequence was further investigated using an animal model of choroidal neovascularisation where a krypton laser was used to produce a wound healing response in the choroid and retina. The oligonucleotide was injected into the vitreous and the development of choroidal neovascularisation assessed using fluorescein angiography.
Results:
The targeted sequence was shown in vitro to downregulate the VEGF produced by RPE cells grown under hypoxic conditions and when injected into laser treated eyes was shown to be preferentially taken up in the laser lesion. Fluorescein angiography demonstrated that the test oligonucleotide was successful in reducing laser-mediated choroidal neovascularisation.
Conclusions:
A sequence corresponding to the 5'UTR of the VEGF gene has provided encouraging results for the treatment of neovascularisation.
Insights
Targeted oligonucleotides effectively reduced vascular endothelial growth factor (VEGF) production in vitro and inhibited choroidal neovascularization in vivo, offering a potential treatment for neovascular eye diseases.
Area of Science:
- Ophthalmology
- Molecular Biology
- Genetics
Background:
- Oligonucleotide delivery and efficacy in the ocular environment have been previously established.
- Vascular Endothelial Growth Factor (VEGF) is a key factor in neovascularization, implicated in various eye diseases.
- Targeted oligonucleotide sequences offer a potential therapeutic strategy for controlling VEGF-driven pathologies.
Purpose of the Study:
- To evaluate the efficacy of an oligonucleotide targeting VEGF in reducing VEGF production in vitro.
- To assess the in vivo effect of this oligonucleotide on laser-induced choroidal neovascularization (CNV).
Main Methods:
- In vitro screening of oligonucleotide sequences using retinal pigment epithelial (RPE) cells under hypoxic conditions.
- In vivo assessment using a laser-induced CNV animal model.
- Intravitreal injection of the targeted oligonucleotide and evaluation via fluorescein angiography.
Main Results:
- The targeted oligonucleotide demonstrated in vitro downregulation of VEGF production by RPE cells.
- Preferential uptake of the oligonucleotide was observed in laser-induced lesions in vivo.
- Successful reduction of laser-mediated choroidal neovascularization was confirmed by fluorescein angiography.
Conclusions:
- An oligonucleotide targeting the 5'UTR of the VEGF gene shows promise for treating neovascularization.
- This approach offers a potential therapeutic avenue for neovascular eye conditions.
- Further research into VEGF-targeted oligonucleotides is warranted for clinical application.
