Experimental gene transfer to the corneal endothelium

Transfer of cDNA to corneal endothelial cells has been demonstrated in cell monolayers in vitro, in endothelium of whole thickness corneas ex vivo and following intracameral injection. Studies examining the feasibility and optimal methods for gene transfer to the cornea have used viral and non-viral vectors, initially histochemical or fluorescent marker genes, and in endothelium of numerous species ranging from mouse to man. As the feasibility of genetic modification of corneal endothelial cells has been successfully demonstrated in a number of cell culture and animal models, there is significant potential for gene transfer in the treatment of human corneal endothelial disease. The two most widely studied applications of gene transfer to endothelium are (i) transduction of immunomodulatory genes to donor corneal endothelium prior to transplantation as a strategy to delay allogeneic rejection and (ii) modulation of apoptosis or induction of replication in human corneal endothelial cells to increase cell density. Although continued improvements in vectors for gene transfer will improve the efficacy and safety of gene therapy, more detailed understanding of the altered biology of endothelium in disease will be necessary to allow selection of appropriate targets for a gene-based treatment approach.

► Corneal endothelium gene therapy includes transfer of cDNA and inhibitory RNA.
► Gene transfer is feasible in endothelial cells in vitro, and whole corneas ex vivo.
► Two experimental approaches show significant potential for endothelial gene therapy:
► (1) Transfer of immunomodulatory genes to prevent transplant rejection.
► (2) Transfer of genes modulating cell division or survival to increase cell density.