Speaker
Descrizione
Vision is the most dominant human sense and the visual system represents a sensitive marker of biological and physical insults. Here, we exploited this system to compare the effects of ultra-high dose rate radiotherapy (FLASH) and conventional dose rate irradiation (CONV) in healthy C57BL/6 mice and in a preclinical models of ocular melanoma and glioblastoma. Irradiations were performed with a new-generation linear accelerator (LINAC) capable of alternating between FLASH and CONV modalities, enabling a direct comparison of regimens.
We analyzed two critical levels of the visual pathway: the retina, where photo-transduction and radiation toxicity often initiate, and the primary visual cortex, where visual signals are processed. In healthy animals, FLASH markedly reduced retinal inflammation, with lower microglial activation and decreased expression of molecular stress markers, and modulated cortical responses in a dose-dependent manner. Both in melanoma and glioblastoma model, FLASH and CONV showed comparable efficacy in reducing tumor size, yet FLASH better preserved the integrity of non-tumoral tissues. Importantly, both retina and cortex displayed dose-dependent sensitivity to irradiation, underscoring the visual system as a highly responsive readout for treatment-induced effects.
These findings demonstrate that FLASH radiotherapy can mitigate radiation-induced toxicity in the visual system without compromising tumor control. By preserving retinal and cortical integrity while maintaining antitumor efficacy, FLASH emerges as a promising therapeutic approach for ocular melanoma and potentially other conditions where vision preservation is critical.
