| Popis: |
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. |
