Elucidating the Corneal Endothelial Cell Proliferation Capacity through an Interspecies Transcriptome Comparison

The regenerative capacity of corneal endothelial cells (CECs) differs between species; in bigger mammals, CECs are arrested in a non-proliferative state. Damage to these cells can compromise their function causing corneal opacity. Corneal transplantation is the current treatment for the recovery of clear eyesight, but the donor tissue demand is higher than the availability and there is a need to develop novel treatments. Interestingly, rabbit CECs retain a high proliferative profile and can repopulate the endothelium. There is a lack of fundamental knowledge to explain these differences. Gaining information on their transcriptomic variances could allow the identification of CEC proliferation drivers. In this study, human, sheep, and rabbit CECs are analyzed at the transcriptomic level. To understand the differences across each species, a pipeline for the analysis of pathways with different activities is generated. The results reveal that 52 pathways have different activity when comparing species with non-proliferative CECs (human and sheep) to species with proliferative CECs (rabbit). The results show that Notch and TGF-beta pathways have increased activity in species with non-proliferative CECs, which might be associated with their low proliferation. Overall, this study illustrates transcriptomic pathway-level differences that can provide leads to develop novel therapies to regenerate the corneal endothelium.