RETINAL FUNCTIONAL CHANGE CAUSED BY ADENOVIRAL VECTOR-MEDIATED TRANSFECTION OF LACZ GENE

We examined the effect of insertion of an exogenous gene on retinal fu nction to assess the rationale of adenoviral vector-mediated gene tran sfer for future gene therapy, An adenoviral vector expressing bacteria l LacZ (AdCALacZ) was injected into the eyes of adult rats either intr avitreally (group A) or subretinally (group B), and the gene expressio n and retinal function were thus examined at different time points aft er gene transfer for 3 weeks. X-Gal histostaining showed that neural r etinal cells were transfected in group A and that retinal pigment epit helial cells were transfected in group B. The gene transfer was more e fficient in group B (54.4% of the fixed retinal area was stained) than ire group A (10.4%). The electroretinogram (ERG) revealed retinal dys function in the AdCALacZ-transfected rats even at the stage in which t he histological damage was not apparent by electron microscopy and imm unohistochemical studies for cytokeratin, S-100 protein, and glial fib rillary acidic protein. The ERG change was correlated with the intensi ty of inflammation, and retinal function recovered to the original lev el by 3 weeks, along with a diminution of inflammation. Functional cha nges were more evident in eyes treated with AdCALacZ than in those inf ected with adenoviral vector with no exogenous gene; however, no histo logical difference was observed between these groups, indicating that the insertion of exogenous gene itself affects retinal function. The r esults showed that different kinds of retinal cells could be gene-tran sferred by an adenoviral vector, depending on the application method. The retinal dysfunction caused by each adenoviral transfection method was caused by inflammation and the insertion of exogenous gene, and th is retinal dysfunction was recoverable. In future gene therapy, specia l attention should be given to the method of exogenous gene insertion in the retina.