Photobiomodulation (PBM) therapy is the use of light with specific sub-thermal radiometric and spectral conditions to heal tissues. Its mechanism is not yet fully understood and PBM conditions are rarely optimized. Our recent in vitro and in vivo observations indicated that PBM: i) increases the tissue oxygen (O2) consumption following hypoxia, ii) promotes angiogenesis in vivo, iii) increases, following an application of 5-aminolevulinic acid, the endogenous production of protoporphyrin IX (PPIX), which can be used as an O2 sensor, and is a photosensitizer approved for cancer detection and therapy. From these observations, we derived three sub-projects:
1) to optimize PBM through an extensive exploration of the radiometric and spectral conditions in real-time, with and without administration of exogenous agents, using a fast novel approach based on the time-resolved luminescence spectroscopy of PPIX (to measure the O2 partial pressure (pO2) as well as cofactors reflecting the metabolism such as NAD(P)H and FAD+;
2) to validate the conditions found to be optimal in vitro (cell proliferation and migration assay) and in vivo, looking at the macroscopic effects of PBM on angiogenesis;
3) to better understand the PBM mechanism by looking in vitro at: gene expression; PPIX production, cytokine changes, ATP and growth factor production; and PBM action spectra.
This project is performed in collaboration with the department of vascular surgery at the Lausanne’s CHUV university hospital (Dr. F. Allagnat and PD-MERClin Dr. S. Déglise).
This project will have a significant impact on the fundamental understanding of PBM and in PBM’s (bio)medical applications: I. The benefits of promoting angiogenesis to ischemic tissues by PBM is essential in many diseases, for instance in the case of diabetic ulcers; II. Similarly, rescuing by PBM tissue subject to dysfunction of its mitochondrial metabolism is a promising approach to treat many chronic diseases, including neurodegenerative diseases, as we have shown both in PINK1 fruit flies and in a Parkinson’s disease rat model; III. Increasing the endogenous ALA-induced PPIX production by PBM will help to improve PPIX’s therapeutic and diagnostic performance, for instance in the detection and removal of glioblastoma, and broaden its applications.