Understanding pericytes to better treat vision loss

The research led by Alexandre Dubrac  stems from his deep interest in the vascular system and especially capillaries, the tiny blood vessels that play a vital role in keeping organs functioning properly. More specifically, he studies pericytes, often overlooked cells that are essential to capillary health.

Found in large numbers in organs like the brain and eye, pericytes play a supporting role for the endothelial cells that make up the capillaries. Pericyte dysfunction is now recognized as a major factor in several diseases including retinopathies linked to prematurity or diabetes. These conditions lead to vision loss caused by poor vascularization and uncontrolled inflammation—processes in which pericytes may be more actively involved than previously thought.

To better understand their role, Alexandre Dubrac and his team at the Centre de recherche du CHU Sainte-Justine affiliated to Université de Montréal, developed transgenic mouse models and used cutting-edge technology like single-cell sequencing, which analyzes the genetic material of individual cells. The findings showed that pericytes are far more than passive cells. In fact, they accompany endothelial cells in pathological processes and can even become diseased themselves. The researchers also identified new pericyte populations involved in fibrosis, a type of excessive scarring that contributes to vision loss.

The discoveries pave the way for promising clinical applications. Specific markers found in the pathological pericytes identified in the study could be used to develop more sensitive diagnostic tools and allow for more accurate risk stratification in patients. In the long term, the research could help advance precision medicine for the treatment of vascular eye diseases by fostering the development of therapies that target not only the endothelium but also its key partners the pericytes.

References

• Zarkada, G., Howard, J. P., Xiao, X., Park, H., Bizou, M., Leclerc, S., Künzel, S. E., Boisseau, B., Li, J., Cagnone, G., Joyal, J.-S., Andelfinger, G., Eichmann, A., et Dubrac, A. (2021). Specialized endothelial tip cells guide neuroretina vascularization and blood-retina-barrier formation. Developmental Cell, 56(15), 2237-2251.e6. https://doi.org/10.1016/j.devcel.2021.06.021
• Dubrac, A., Künzel, S. E., Künzel, S. H., Li, J., Chandran, R. R., Martin, K., Greif, D. M., Adams, R. H., et Eichmann, A. (2018). NCK-dependent pericyte migration promotes pathological neovascularization in ischemic retinopathy. Nature Communications, 9, article 3463. https://doi.org/10.1038/s41467-018-05926-7