In vivo use of oligonucleotides to inhibit choroidal neovascularisation inthe eye

Background We have previously demonstrated the in vivo uptake of oligonucle otides in the rat eye and have continued with experiments to look at the ef fectiveness of targeted oligonucleotide sequences. Vascular endothelial gro wth factor (VEGF) is correlated with new blood vessel formation and has bee n implicated in numerous eye diseases characterised by abnormal blood vesse l proliferation. An oligonucleotide targeted to the VEGF sequence was exami ned for its effect on VEGF production in vitro and the development of choro idal 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 o f choroidal neovascularisation where a krypton laser was used to produce a wound healing response in the choroid and retina. The oligonucleotide was i njected into the vitreous and the development of choroidal neovascularisati on assessed using fluorescein angiography. Results The targeted sequence was shown in vitro to downregulate the VEGF p roduced by RPE cells grown under hypoxic conditions and when injected into laser treated eyes was shown to be preferentially taken up in the laser les ion. 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 prov ided encouraging results for the treatment of neovascularisation. Copyright (C) 2001 John Wiley & Sons, Ltd.