Gene transfer by viral vectors into blood vessels in a rat model of retinopathy of prematurity

Aims - To test the feasibility of gene transfer into hyaloid blood vessels and into preretinal neovascularisation in a rat model of retinopathy of pre maturity (ROP), using different viral vectors. Methods - Newborn rats were exposed to alternating hypoxic and hyperoxic co nditions in order to induce ocular neovascularisation (ROP rats). Adenoviru s, herpes simplex, vaccinia, and retroviral (MuLV based) vectors, all carry ing the beta galactosidase (beta -gal) gene, were injected intravitreally o n postnatal day IS (PIS). Two sets of controls were also examined: P18 ROP rats injected with saline and P18 rats that were raised in room air before the viral vectors or saline were injected. Two days after injection, the ra ts were killed, eyes enucleated, and beta -gal expression was examined by X -gal staining in whole mounts and in histological sections. Results - Intravitreal injection of the adenovirus and vaccinia vectors yie lded marked beta -gal expression in hyaloid blood vessels in the rat ROP mo del. Retinal expression of beta -gal with these vectors was limited almost exclusively to the vicinity of the injection site. Injection of herpes simp lex yielded a punctuate pattern of beta -gal expression in the retina but n ot in blood vessels. No significant beta -gal expression occurred in rat ey es injected with the retroviral vector. Conclusions - Adenovirus is an efficient vector for gene transfer into bloo d vessels in an animal model of ROP. This may be a first step towards utili sing gene transfer as a tool for modulating ocular neovascularisation for e xperimental and therapeutic purposes.