Establishing Xenopus laevis as an in vivo model system for investigating the effect of photobiomodulation therapy in oral mucositis

About This Grant

Project Abstract Cancer therapies can lead to the development of oral mucositis (OM) leading to ulceration of the oral epithelium. The painful side effects of OM may result in serious infections, cancer treatment cessation, and loss of eating and nutritional intake. Photobiomodulation therapy (PBMT) is a therapeutic strategy to prevent and treat chemotherapy-induced OM by promoting wound healing and inhibiting inflammation. It has been demonstrated that PBMT can induce a biphasic response where increasing doses result in better outcomes until a threshold is reached where additional doses not only dampen the response but can elicit further tissue damage. During PBMT, the photonic energy induces the release of reactive oxygen species (ROS) and other signaling molecules triggering a signaling cascade that promotes cell migration and proliferation. However, the precise downstream signaling mechanisms elicited by ROS remain unclear. The objective of the proposed research is to establish an in vivo model system using Xenopus laevis tadpole tail regeneration to evaluate the mechanisms and efficacy of PBMT. Our first hypothesis is that different combinations of PBMT parameters, including irradiance, treatment time, fluence, and wavelength, will result in a biphasic Xenopus tail regeneration response. Our second hypothesis is that PBMT will initiate a unique signaling cascade that is dependent on the release of ROS to improve wound healing. We plan on addressing these hypotheses through a variety of in vivo biochemical approaches. Following amputation, Xenopus tadpole tails will be irradiated with varying combinations of PBMT parameters to determine how they affect wound healing. We will also utilize a transgenic Xenopus line that allows for the in vivo visualization of intracellular ROS levels. The use of ROS inhibitors and activators in this model system will determine the requirement of ROS release for PBMT-induced wound healing. To further delineate downstream signaling initiated by PBMT, bulk RNA Sequencing will be employed to identify novel pathways utilized in this wound healing response. The proposed work is important because it will elucidate potential therapeutic targets that can be used in combination with PBMT to enhance its health- promoting effects. Also, optimization of this in vivo model system will provide a reproducible and cost-effective strategy to evaluate the mechanisms of PBMT for a variety of other applications including nervous system conditions, musculoskeletal disorders, skin and mucosal conditions, cancers, and bone and joint disorders, in additional to its oral applications.