Gene transfer to the nonhuman primate retina with recombinant feline immunodeficiency virus vectors.
We hypothesize that recombinant feline immunodeficiency viral (rFIV) vectors may be useful for gene transfer to the nonhuman primate retina. We performed vitrectomies and subretinal injections in the right eyes of 11 cynomolgus monkeys. Vesicular stomatitis virus glycoprotein-pseudotyped rFIV that expressed the Escherichia coli beta-galactosidase gene was injected into eight eyes. Sham vehicle or lactose buffer injections were also performed in two of these eight study eyes. rFIV pseudotyped with an amphotropic envelope was used in two eyes, and in one animal injections of lactose buffer only were given. After surgery the animals were clinically evaluated by retinal photography and electroretinography. beta-Galactosidase expression was evaluated, at a final end point, in histological sections. We found photoreceptor and Müller cells to have the greatest transgene expression. Focal inflammatory responses localized to the injection site were seen histologically in all eyes. No difference in transduction efficiency was seen between injections near the macula and more peripheral injections. Visual function as assessed by electroretinography was not significantly affected by vector or vehicle injections. We conclude that rFIV vectors administered beneath the retina can transduce a variety of retinal cells in the nonhuman primate retina. rFIV vectors have therapeutic potential and could be exploited to develop gene therapy for the human eye.
Lotery
Andrew J
AJ
Department of Ophthalmology and Visual Sciences, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242, USA. andrew-lotery@uiowa.edu
Derksen
Todd A
TA
Russell
Stephen R
SR
Mullins
Robert F
RF
Sauter
Sybille
S
Affatigato
Louisa M
LM
Stone
Edwin M
EM
Davidson
Beverly L
BL
D000818:Animals; D015870:Gene Expression; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000235:genetics / Q000502:physiology*; D006801:Humans; D016089:Immunodeficiency Virus, Feline / Q000235:genetics / Q000502:physiology*; D008252:Macaca fascicularis; D008562:Membrane Glycoproteins; D011323:Primates; D011995:Recombination, Genetic; D012160:Retina; D014759:Viral Envelope Proteins / Q000235:genetics; D001616:beta-Galactosidase / Q000235:genetics
C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; D001616:beta-Galactosidase