An immune response after intraocular administration of an adenoviral vector containing a beta galactosidase reporter gene slows retinal degeneration in the rd mouse

Background/aims-Retinal degenerations are a leading cause of blindness for which there are currently no effective treatments. This has stimulated inte rest in the investigation of gene therapy strategies for these diseases in a variety of animal models. A number of attempts have been made to prevent photoreceptor loss in the rd mouse model of retinal degeneration using aden oviral vectors containing either a copy of the missing functional gene or a gene encoding either a neurotrophic factor or an antiapoptotic factor. The authors have previously demonstrated that intraocular administration of an adenoviral vector containing a beta galactosidase gene (AV.LacZ) results i n an immune response to viral gene products and beta galactosidase. Here th e effect of the immune response on retinal degeneration is examined. Methods-Juvenile rd mice were injected intravitreally with AV.LacZ and a pr oportion were depleted of either CD4+ or CD8+ T cells or both. Control anim als were injected with PBS. The mice were sacrificed 10 and 20 days post-in jection and their eyes embedded in paraffin wax and sectioned. Results-10 days after intravitreal injection of AV.LacZ, the outer nuclear layer contains an average of 2.5 rows compared with 1.5 in PBS injected ani mals (p<0.005). The protective effect of AV.LacZ is negated by immune suppr ession and does not extend beyond 20 days. Conclusion-An immune response to vector and transgene products is able to s low degeneration in the rd mouse. This phenomenon should be taken into acco unt when analysing the degeneration in the rd mouse following gene transfer .