Abstract
The corneal endothelium is the inner layer of the cornea. Despite comprising only a monolayer of cells, dysfunction of this layer renders millions of people visually impaired worldwide. Currently, corneal endothelial transplantation is the only viable means of restoring vision for these patients. However, because the supply of corneal endothelial grafts does not meet the demand, many patients remain on waiting lists, or are not treated at all. Possible alternative treatment strategies include intracameral injection of human corneal endothelial cells (HCEnCs), biomedical engineering of endothelial grafts and increasing the HCEnC density on grafts that would otherwise have been unsuitable for transplantation. Unfortunately, the limited proliferative capacity of HCEnCs proves to be a major bottleneck to make these alternatives beneficial. To tackle this constraint, proliferation enhancing genetic engineering is being investigated. This review presents the diverse array of genes that have been targeted by different genetic engineering strategies to increase the proliferative capacity of HCEnCs and their relevance for clinical and research applications. Together these proliferation-related genes form the basis to obtain a stable and safe supply of HCEnCs that can tackle the corneal endothelial donor shortage.
Highlights
When light enters the eye, the first tissue it passes through is the cornea
ZO-1 short hairpin RNA (shRNA) only increased the amount of Human corneal endothelial cells (HCEnCs) significantly on full-thickness donor grafts with a relatively low endothelial cell density (ECD), independent of age, while this was not reported in the cells overexpressing ZONAB [12]
These results indicate that a downregulation of ZO-1 by RNA interference (RNAi) is not sufficient to promote HCEnC proliferation in the presence of contact inhibition
Summary
When light enters the eye, the first tissue it passes through is the cornea. This highly specialized transparent tissue is comprised of 5 anatomical layers; the epithelium, Bowman’s layer, stroma, Descemet’s membrane and its most posterior layer, the endothelium. The expression of SV40 large T-antigen in HCEnCs resulted in an increased proliferation rate and extended survival of HCEnCs from both old and young donors [26,27,28,29]. These TERT-transfected cells exhibited many HCEnC-associated characteristics including contact inhibition, presence of ZO-1 and N-cadherin on protein level and an intact Na+/K+-ATPase pump function.
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