Di Marco Beatrice, Sansevero Gabriele, D'Orsi Beatrice, De Santis Elisa, Salamone Giulia, Cavalieri Andrea, Masturzo Luigi, Celentano Mariagrazia, Di Martino Fabio, Capaccioli Simone, Panetta Daniele, Paiar Fabiola, Gonnelli Alessandra, Gadducci Giovanni, Costa Mario, Strettoi Enrica
National Research Council-Institute of Neuroscience, Via Moruzzi 1, Pisa, 56124, Italy.
Regional Doctorate School in Neuroscience, University of Florence, Florence, Italy.
Sci Rep. 2025 Jul 2;15(1):22938. doi: 10.1038/s41598-025-06101-x.
The retinal pigment epithelium (RPE) is a fundamental monolayer of pigmented cells that supports visual function, situated between the neural retina and choroidal blood vessels. Radiotherapy is a common treatment for ocular tumors such as uveal melanoma; however, the RPE is inevitably exposed to radiation during treatment. FLASH radiotherapy, characterized by ultra-high dose-rates, has emerged as a promising approach to minimize normal tissue toxicity while maintaining tumor control. Despite its potential, few preclinical studies have explored the effects of FLASH irradiation on the RPE, and no studies have directly compared FLASH with conventional (CONV) radiotherapy in this context. Using a LINAC capable of switching between FLASH and CONV irradiation, we here address the radiobiological effects on ARPE-19 cells, an in vitro RPE model, and the RPE of living mice. FLASH treatment demonstrated protective effects on ARPE-19 cells, enhancing cell viability and modulating cytokine expression (e.g., IL-6, IL-8). Furthermore, RPE tissue exhibited dose-dependent radiation sensitivity, with FLASH-irradiated mice performing better than CONV-treated ones. These findings indicate that FLASH radiotherapy may protect the RPE during ocular tumor treatment and provide insights into tissue-specific radiation sensitivity in the eye, supporting further research into its clinical applications.
视网膜色素上皮（RPE）是一层位于神经视网膜和脉络膜血管之间的色素细胞单层结构，对视觉功能起支持作用。放射治疗是葡萄膜黑色素瘤等眼部肿瘤的常见治疗方法；然而，在治疗过程中RPE不可避免地会受到辐射。具有超高剂量率特点的FLASH放射治疗已成为一种有前景的方法，可在维持肿瘤控制的同时将正常组织毒性降至最低。尽管有其潜力，但很少有临床前研究探讨FLASH照射对RPE的影响，在此背景下也没有研究直接将FLASH与传统（CONV）放射治疗进行比较。我们使用一台能够在FLASH和CONV照射之间切换的直线加速器，在此研究了对ARPE - 19细胞（一种体外RPE模型）和活体小鼠RPE的放射生物学效应。FLASH治疗对ARPE - 19细胞显示出保护作用，提高了细胞活力并调节了细胞因子表达（如IL - 6、IL - 8）。此外，RPE组织表现出剂量依赖性辐射敏感性，接受FLASH照射的小鼠比接受CONV治疗的小鼠表现更好。这些发现表明，FLASH放射治疗可能在眼部肿瘤治疗期间保护RPE，并为眼部组织特异性辐射敏感性提供见解，支持对其临床应用的进一步研究。
