Adeno-associated and herpes simplex viruses as vectors for gene transfer to the corneal endothelium

Purpose. We examined the efficacy and cytopathogenicity of adeno-associated (AAV) and herpes simplex viruses (HSV) as vectors for gene transfer to cor neal endothelial cells (CECs). Methods. Recombinant AAV and HSV were examin ed for their ability to deliver a lacZ histochemical marker gene to whole-t hickness rabbit and human corneas ex vivo. Transgene expression was detecte d with histochemistry and quantified by a colorimetric assay. Results, Rabb it and human corneas transduced with AAV showed increasing numbers of cells expressing marker gene over a 3- to 4-week period. Using 2.5 x 10(6) or 1. 5 x 10(7) infective units for rabbit and human corneal specimens, respectiv ely, similar to 2% of CECs expressed the reporter gene. HSV (10(6) plaque-f orming units/ specimen) transduced similar to 5% of rabbit and human CECs b ut showed cytotoxicity. In contrast to the duration of recombinant AAV-medi ated lacZ expression, recombinant HSV expression was maximal at day 1 and d eclined to low levels at day 7. Conclusion. AAV is a promising vector, but its usefulness for corneal transduction is currently limited by the technic al difficulties preparing high titres. The HSV vector examined is efficient but needs further genetic modification to prolong transgene expression and reduce its toxicity.