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.