Abstract
Purpose: :
To investigate the potential advantages using novel simian immunodeficienty virus vector pseudotyped with Sendai virus F and HN proteins (SeV-F/HN-SIV vector) for retinal gene therapy in a mouse model of choroidal neovascularization (CNV).
Methods: :
SeV-F/HN-SIV vector or conventional VSV-G-pseudotyped SIV (VSV-G-SIV) vector was injected into subretinal space of adult C57BL/6 mice, and the transgene expression was compared between the groups with simple injection and removal 5 minutes after injection. CNV was induced by laser photocoagulation in the eyes treated with SeV-F/HN-SIV vector encoding pigment epithelium-derived factor (PEDF) or soluble fms-like tyrosine kinase-1 (sFlt-1). The CNV area was measured by image analysis at 2 weeks after laser injury. The effect of PEDF and sFlt-1 on normal retina was assessed by histological examination.
Results: :
Only 5 minutes of retinal detachment (RD) following SeV-F/HN-SIV vector injection resulted in high-level gene transfer to retinal pigment epithelium, while over several hours of RD was required in use of VSV-G-SIV vector. The transgene expression was maintained over a 1-year period. SeV-F/HN-SIV-mediated retinal delivery of PEDF or sFlt-1 significantly suppressed laser-induced CNV. Long-term expression of PEDF for 6 months showed no apparent change in retinal structure; however that of sFlt-1 resulted in photoreceptor degeneration.
Conclusions: :
SeV-F/HN-SIV vector enables effective retinal gene transfer by brief exposure. SeV-F/HN-SIV-mediated retinal delivery of PEDF may be an effective approach to the treatment of CNV with broader safety range.
Keywords: gene transfer/gene therapy • retina • age-related macular degeneration