Adenovirus-mediated gene transfer to retinal ganglion cells.

PURPOSE To evaluate the capacity of a replication-defective adenoviral vector to transport retrogradely from the superior colliculus to the nuclei of retinal ganglion cells and to express in these cells vector-encoded transgene. METHODS A replication-deficient adenovirus encoding an expression cassette for the Escherichia coli gene lacZ was injected into the right superior colliculus of mice. Brain sections and both eyes were tested histochemically and/or immunohistochemically for E. coli beta-galactosidase (LacZ) activity at 3, 7, 14, and 30 days after injection. RESULTS lacZ expression was detected in the retinal ganglion cells of the contralateral eye at 7, 14, and 30 days after injection, but no expression was observed in the retina at 3 days after injection. No signs of retinal pathology was observed histologically. LacZ-positive cells also were found in other afferent systems to the superior colliculus, such as the reticular formation, layer V of the ipsilateral visual cortex, and pars reticulata of the ipsilateral substantia nigra. CONCLUSIONS Injection of an adenovirus vector into the superior colliculus is an effective means to transfer and express a gene in retinal ganglion cells while avoiding damage to the eye tissues; thus, it represents a potentially useful tool to manipulate gene expression selectively in the retina.