The future of keratoplasty: cell-based therapy, regenerative medicine, bioengineering keratoplasty, gene therapy.

Abstract

To provide an update on the state of development of novel therapeutic modalities for the treatment of corneal diseases. Novel corneal therapeutics may be broadly classified as cell therapy, regenerative medicine, bioengineered corneal grafts and gene therapy. Cell therapy encompasses cultivation of cells, such as corneal endothelial cells (CECs) and keratocytes to replenish the depleted native cell population. Regenerative medicine is mainly applicable to the corneal endothelium, and is dependent on the ability of native, healthy CECs to restore the corneal endothelium following trauma or descemetorhexis; this approach may be effective for the treatment of Peter's anomaly and Fuchs endothelial corneal dystrophy (FECD). Bioengineered corneal grafts are synthetic constructs designed to replace cadaveric corneal grafts; tissue-engineered endothelial-keratoplasty grafts and bioengineered stromal grafts have been experimented in animal models with favourable results. Gene therapy with antisense oligonucleotide and CRISPR endonucleases, including deactivated Cas9, may potentially be used to treat FECD and TGFBI-related corneal dystrophies. These novel therapeutic modalities may potentially supersede keratoplasty as the standard of care in the future.