Simian Lentiviral Vector–mediated Retinal Gene Transfer of FGF2 Protects Histological Degeneration and Electrical Defect for the Long Period in Two Different Models of Retinitis Pigmentosa

Abstract

Abstract: : Purpose: Lentivirus vector, having a feature of long–term gene expression, is expected as a useful therapeutic method for slowly progressive retinal degeneration. We recently developed a novel lentivirus vector derived from the non–pathogenic simian immunodeficiency virus (SIV), and have demonstrated that SIV vector can be efficiently and safely applicable to retinal gene transfer and have highly therapeutic effect following PEDF gene expression in RCS rats. We assessed the effect of SIV–mediated subretinal gene transfer of basic fibroblast growth factor (FGF2), a potent neurotrophic factor, during the disease progression in two different animal models, RCS rats and rds mice. Methods: Vector injection into the peripheral subretinal space of 3 weeks old RCS rats and rds mice was performed. Histopathological and electroretinographic (ERG) assessment were examined at several periods up to 24 weeks after gene transfer. Results: In RCS rats, FGF2 gene transfer significantly protected the loss of PCs corresponding to the regions of the gene transfer compared to those of control groups until 8 weeks after gene transfer. B–waves of ERGs were significantly observed in the group of SIV–FGF2 treated rats. In rds mice, similarly, histological photoreceptor cell loss and electroretinographical functional defect were significantly prevented at 24 weeks after gene transfer. Conclusions: SIV–medeated gene transfer of FGF2 can protect the retinal degeneration and functional defects in two different animal models for a long period. These results support the utility of this neuroprotective gene thrapy against RP, caused by various gene mutations.

Keywords: gene transfer/gene therapy • retinal degenerations: hereditary • retinal pigment epithelium