Centre de Recherche des Cordeliers, INSERM UMRS 1138, Sorbonne Université, Physiopathology of Ocular Diseases: Therapeutic Innovations, 15 rue de l'école de Médecine, Paris, 75006, France.
Ocular Oncology Department, Institut Curie, 26 rue d'Ulm, Paris, 75005, France.
J Neuroinflammation. 2024 Jun 24;21(1):162. doi: 10.1186/s12974-024-03151-2.
Radiation retinopathy (RR) is a major side effect of ocular tumor treatment by plaque brachytherapy or proton beam therapy. RR manifests as delayed and progressive microvasculopathy, ischemia and macular edema, ultimately leading to vision loss, neovascular glaucoma, and, in extreme cases, secondary enucleation. Intravitreal anti-VEGF agents, steroids and laser photocoagulation have limited effects on RR. The role of retinal inflammation and its contribution to the microvascular damage occurring in RR remain incompletely understood. To explore cellular and vascular events after irradiation, we analyzed their time course at 1 week, 1 month and 6 months after rat eyes received 45 Gy X-beam photons. Müller glial cells, astrocytes and microglia were rapidly activated, and these markers of retinal inflammation persisted for 6 months after irradiation. This was accompanied by early cell death in the outer retina, which persisted at later time points, leading to retinal thinning. A delayed loss of small retinal capillaries and retinal hypoxia were observed after 6 months, indicating inner blood‒retinal barrier (BRB) alteration but without cell death in the inner retina. Moreover, activated microglial cells invaded the entire retina and surrounded retinal vessels, suggesting the role of inflammation in vascular alteration and in retinal cell death. Radiation also triggered early and persistent invasion of the retinal pigment epithelium by microglia and macrophages, contributing to outer BRB disruption. This study highlights the role of progressive and long-lasting inflammatory mechanisms in RR development and demonstrates the relevance of this rat model to investigate human pathology.
放射性视网膜病变 (RR) 是眼肿瘤经敷贴治疗或质子束治疗后发生的主要副作用。RR 表现为迟发性、进行性的微血管病变、缺血和黄斑水肿，最终导致视力丧失、新生血管性青光眼，在极端情况下，还会导致眼球摘除。玻璃体内抗血管内皮生长因子 (VEGF) 药物、皮质类固醇和激光光凝对 RR 的疗效有限。视网膜炎症的作用及其对 RR 中发生的微血管损伤的贡献仍不完全清楚。为了探讨照射后的细胞和血管事件，我们分析了大鼠眼接受 45Gy X 射线光子照射后 1 周、1 个月和 6 个月时的时间进程。Müller 胶质细胞、星形胶质细胞和小胶质细胞迅速被激活，这些视网膜炎症的标志物在照射后持续存在 6 个月。这伴随着外视网膜早期的细胞死亡，这种细胞死亡在以后的时间点持续存在，导致视网膜变薄。照射 6 个月后，观察到小视网膜毛细血管的延迟性丧失和视网膜缺氧，表明内血-视网膜屏障 (BRB) 改变，但内视网膜没有细胞死亡。此外，激活的小胶质细胞侵入整个视网膜并包围视网膜血管，表明炎症在血管改变和视网膜细胞死亡中起作用。辐射还引发了小胶质细胞和巨噬细胞对视网膜色素上皮的早期和持续侵袭，导致外 BRB 破坏。这项研究强调了进行性和持久的炎症机制在 RR 发展中的作用，并证明了这种大鼠模型对研究人类病理学的相关性。
