IN-VIVO TRANSFER OF A REPORTER GENE TO THE RETINA MEDIATED BY AN ADENOVIRAL VECTOR

Purpose. The ability of replication-deficient adenovirus to mediate ge ne transfer to retinal cells was evaluated. Methods. A replication-def icient adenoviral vector, AdCMV beta A.ntlacZ, which contains the bact erial beta-galactosidase (lacZ) reporter gene, was injected into the s ubretinal space of normal, rd, and rds strains of mice at various ages . The efficiency and duration of transgene expression were assessed by histochemical examination and transmission electron microscopy. Resul ts. AdCMV beta A.ntlacZ was effective in mediating gene transfer to th e retinal pigment epithelial cells, rod and cone photoreceptor cells, and cells in the inner nuclear layer of the retina for periods of up t o 1 month. Gene transfer to retinal pigment epithelial cells occurred at much lower viral titers than was required for gene transfer to phot oreceptor cells. The extent to which photoreceptor cells could be tran sduced varied with the age of the animals and the conditions of the ph otoreceptor cells: greater numbers of photoreceptor cells were transdu ced in 5- to 7-day-old pups and in mice at the initial stages of photo receptor degeneration than in normal adult mice. No evidence of gross pathogenic effects or viremia in recipient mice was observed. Conclusi ons. Replication-deficient adenovirus mediates transfer and expression of a foreign gene in retinal pigment epithelial and photoreceptor cel ls. Gene transfer to photoreceptor cells is enhanced in developing ret inas or at the predegenerate stage of photoreceptors in genetically pr ogrammed retinal degeneration.