2020 Brain Star Award Winner: Dr. François Binet

 

Neutrophils play an active role in retinas of patients undergoing proliferative retinopathies

The retina is a thin layer of nervous tissue at the back of the eye that transforms light into neuronal signals. The retina is essential for vision and is supported by a networks of small blood vessels. In diabetic retinopathy, a common cause of vision loss, these blood vessels degenerate and regrow in an aberrant manner. Such degeneration and regrowth can compromise the functioning of retinal nerve cells. In this ground-breaking publication, François Binet and collaborators describe how neutrophils, a class of white blood cells, play an active role in retinas of patients undergoing proliferative retinopathies (PR).

PRs are characterized by aberrant vascular structures in the eye called neovascular tufts, which can lead to vision loss. Using a model for PR and several complementary experimental approaches to analyse the molecular, cellular and physiological players in the development of PRs, the researchers observed that, after rapid proliferation, cells in diseased blood vessels engaged molecular pathways linked to senescence. These senescent cells summoned an inflammatory response in which neutrophils migrated and accumulated in neovascular tufts in the retina.  In addition, they demonstrated that neutrophils produced molecular “traps” onto diseased vessels to remodel them. This endogenous repair mechanism promoted the elimination of senescent blood vessels and could lead to beneficial vascular remodeling.

In some patients with PR, natural regression of neovascular tufts can occur, but the underlying causes were unknown. This study shows that neutrophils can invade the retina in the later stage of the disease and allow tissue repair through elimination of diseased vascular cells. The selective removal of senescent cells is related to their capacity to attract neutrophils and induce the production of molecular traps.

Thus, this manuscript describes a novel manner by which immune cells clear senescent cells. These findings stress the importance of removing pro-inflammatory senescent cells to allow proper tissue repair. These results also suggest that drugs that promote this process could represent a promising therapeutic avenue for neovascular diseases such as proliferative retinopathies.

François Binet, PhD

This project was initiated when Dr. François Binet was working as a postdoctoral fellow in the laboratory of Dr. Przemyslaw Sapieha at the Hopital Maisonneuve Rosemont Research Center, affiliated with Université de Montréal. As first author of this study, Dr. Binet contributed to the conceptualization of the study and performed most experiments. Furthermore, he analyzed all the data and wrote the manuscript. His responsibilities also included managing communications with collaborators. Finally, he also planned and performed the follow-up experiments to address reviewer comments, along with manuscript editing and correspondence with the editors.

Source of funding:

This work was supported by operating grants from the Canadian Diabetes Association, the Canadian Institutes of Health Research, the Canadian the Heart & Stroke Foundation Canada, the Foundation Fighting Blindness Canada, the Canada Research Chair program and the Natural Sciences and Engineering Research Council of Canada.  P.S. holds the Wolfe Professorship in Translational Research. Collaborators were supported by the Burroughs Wellcome Fund Career Award for Medical Scientists, the Fonds de Recherche du Québec – Santé, the TRANSAT Chair in breast cancer research, MITACs, the Single-Cell Academy (The Vision Health Research Network of Quebec – RRSV), the Antoine Turmel Foundation, the Fonds de Recherche en Ophtalmologie de l’Université de Montréal (FROUM), the Cole Foundation and Hydro-Québec.