Gene transfer by viral vectors into blood vessels in a rat model of retinopathy of prematurity
Itay Chowersa, Eyal Banina, Yitzchak Hemoa, Rinat Poratb, Haya Falkc, Eli Keshetb, Jacob Pe'era, Amos Panetc
a Department of
Ophthalmology, Hebrew University - Hadassah Medical School, Jerusalem,
Israel, b Department of Molecular Biology, c Department of Virology
Correspondence to: Itay Chowers, MD, Department of Ophthalmology, Hadassah University Hospital, PO Box 12000, 91120 Jerusalem, Israel ichowers{at}jhmi.edu
Accepted for publication 1 March 2001
AIMS
To test the
feasibility of gene transfer into hyaloid blood vessels and into
preretinal neovascularisation in a rat model of retinopathy of
prematurity (ROP), using different viral vectors.
METHODSNewborn rats
were exposed to alternating hypoxic and hyperoxic conditions in order
to induce ocular neovascularisation (ROP rats). Adenovirus, herpes
simplex, vaccinia, and retroviral (MuLV based) vectors, all carrying
the 
galactosidase (-gal) gene, were injected intravitreally on
postnatal day 18 (P18). 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 rats were killed, eyes enucleated, and -gal
expression was examined by X-gal staining in whole mounts and in
histological sections.
RESULTSIntravitreal
injection of the adenovirus and vaccinia vectors yielded marked -gal
expression in hyaloid blood vessels in the rat ROP model. Retinal
expression of -gal with these vectors was limited almost exclusively
to the vicinity of the injection site. Injection of herpes simplex
yielded a punctuate pattern of -gal expression in the retina but not
in blood vessels. No significant -gal expression occurred in rat
eyes injected with the retroviral vector.
CONCLUSIONSAdenovirus
is an efficient vector for gene transfer into blood vessels in an
animal model of ROP. This may be a first step towards utilising gene
transfer as a tool for modulating ocular neovascularisation for
experimental and therapeutic purposes.
© 2001 by British Journal of Ophthalmology
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Br. J. Ophthalmol. 2001 85: 891-892.[Extract] [Full Text] [PDF]
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