Proliferation Increasing Genetic Engineering in Human Corneal Endothelial Cells: A Literature Review

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.

The effects of acute angle closure crisis on corneal endothelial cells in patients with type 2 diabetes mellitus

“…Irreversible vision loss will occur if such an injury is not well controlled. Although many studies have investigated the engineering of human corneal endothelial cells in vitro , endothelial damage is still irreversible in vivo ( 27 – 29 ).…”

Unlocking the therapeutic potential of the corneal endothelium: Intravital imaging reveals endogenous regenerative capabilities

“…The current standard of care for treating corneal endothelial dysfunction is penetrating or posterior lamellar keratoplasty, which presents a challenge due to the complexity and cost of the procedure, and worldwide shortages in donor tissue [ 9 , 10 ]. A promising strategy to prevent the disease and restore vision, is to modulate intrinsic molecular pathways to promote corneal endothelial cell proliferation, in order to rejuvenate the tissue [ 11 ]. Modified mRNA technology can be used to transiently alter the protein expression program of cells in vivo, offering an appealing vehicle for the implementation of this therapeutic strategy [ 12 ].…”

Nanoneedles Induce Targeted siRNA Silencing of p16 in the Human Corneal Endothelium

“…Among local gene delivery approaches for the human cornea, [ 19 ] viral transduction still raises immunogenicity and safety concerns, [ 20 ] steering research toward safer nonviral approaches, using lipid based transfection [ 21 ] and electroporation. [ 22,23 ] Those nonviral delivery methods can be effective in vitro and ex vivo but still present cell toxicity, do not provide a localized delivery, and do not efficiently address accessibility challenges in vivo.…”