Loss of vision due to corneal endothelial dysfunction affects millions worldwide and has limited treatment options. Here we present a proof-of-concept for a therapeutic approach that aims to enhance regeneration of the corneal endothelium by inducing proliferation of quiescent cells in vivo, using modified mRNA technology. To test the efficacy of this strategy we developed a mouse model to analyze corneal endothelial regeneration by longitudinal live imaging, using two-photon microscopy. The mouse corneal endothelium displayed complete cellular quiescence and a decline in cell density with aging, consistent with human data. Limited proliferation of corneal endothelial cells was observed during injury repair but was insufficient to restore the tissue to pre-injury levels. Treatment via intracameral injection of five modified mRNAs, encoding for proteins involved in cell cycle activation, induced transient proliferation in corneal endothelial cells in the absence of injury and led to an increase in tissue cell density. This approach may offer a paradigm for enhancing the regenerative response in organs with limited endogenous ability.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.