美国耶鲁大学医学院Eric Song团队的最新研究发现，区隔化眼淋巴系统介导眼脑免疫。相关论文于2024年2月28日发表在《自然》杂志上。

在研究大脑对单纯疱疹病毒的免疫反应时，研究人员观察到玻璃体内的免疫可保护小鼠免受颅内病毒的侵染。这种保护可延伸至细菌甚至肿瘤细胞侵染，玻璃体内的免疫细胞可对胶质母细胞瘤产生治疗性免疫反应。研究进一步发现，眼球的前部和后部有不同的淋巴引流系统，后者通过视神经鞘内的淋巴管道引流到颈深淋巴结。与脑膜淋巴管一样，这种后部淋巴引流也可以通过淋巴刺激器VEGFC调节。

相反，该研究表明，抑制视神经上的淋巴信号可以克服基因治疗中的一个主要局限，即减少对腺病毒的免疫反应，并确保多次给药后疗效的持续性。这些研究结果表明眼球后部和大脑之间能够产生统一的免疫反应共享淋巴回路，揭示了一种未被充分研究的眼部免疫学特征，为眼部和中枢神经系统疾病的治疗策略提供了新的可能。

据了解，在解剖学中眼睛是中枢神经系统（CNS）的延伸，在分子和细胞方面与大脑有许多相似之处。新近的研究表明，大脑的变化往往反映在眼睛上，尤其是视网膜。然而，眼球后部与中枢神经系统其他组织之间可能存在的免疫学关联仍有待揭示。

附：英文原文

Title: Compartmentalized ocular lymphatic system mediates eye–brain immunity

Author: Yin, Xiangyun, Zhang, Sophia, Lee, Ju Hyun, Dong, Huiping, Mourgkos, George, Terwilliger, Gordon, Kraus, Aurora, Geraldo, Luiz Henrique, Poulet, Mathilde, Fischer, Suzanne, Zhou, Ting, Mohammed, Farrah Shalima, Zhou, Jiangbing, Wang, Yongfu, Malloy, Seth, Rohner, Nicolas, Sharma, Lokesh, Salinas, Irene, Eichmann, Anne, Thomas, Jean-Leon, Saltzman, W. Mark, Huttner, Anita, Zeiss, Caroline, Ring, Aaron, Iwasaki, Akiko, Song, Eric

Issue&Volume: 2024-02-28

Abstract: The eye, an anatomical extension of the central nervous system (CNS), exhibits many molecular and cellular parallels to the brain. Emerging research demonstrates that changes in the brain are often reflected in the eye, particularly in the retina1. Still, the possibility of an immunological nexus between the posterior eye and the rest of the CNS tissues remains unexplored. Here, studying immune responses to herpes simplex virus in the brain, we observed that intravitreal immunization protects mice against intracranial viral challenge. This protection extended to bacteria and even tumours, allowing therapeutic immune responses against glioblastoma through intravitreal immunization. We further show that the anterior and posterior compartments of the eye have distinct lymphatic drainage systems, with the latter draining to the deep cervical lymph nodes through lymphatic vasculature in the optic nerve sheath. This posterior lymphatic drainage, like that of meningeal lymphatics, could be modulated by the lymphatic stimulator VEGFC. Conversely, we show that inhibition of lymphatic signalling on the optic nerve could overcome a major limitation in gene therapy by diminishing the immune response to adeno-associated virus and ensuring continued efficacy after multiple doses. These results reveal a shared lymphatic circuit able to mount a unified immune response between the posterior eye and the brain, highlighting an understudied immunological feature of the eye and opening up the potential for new therapeutic strategies in ocular and CNS diseases.

DOI: 10.1038/s41586-024-07130-8

Source: https://www.nature.com/articles/s41586-024-07130-8