Health Management Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Mucosal Immunol. 2021 Jan;14(1):152-163. doi: 10.1038/s41385-020-0282-x. Epub 2020 Mar 16.
Extra-intestinal manifestations (EIMs) of the eyes are found in IBD patients, but the underlying pathogenesis remains unknown. To investigate the pathogenesis of IBD-associated retinal dysfunction, chronic colitis was induced in mice by oral administration of dextran sodium sulfate (DSS). Electroretinography (ERG) was performed to evaluate retinal function. Retinal neuron degeneration was analyzed by immunohistochemistry. Colitic mice displayed aberrant amplitudes of ERG a-, b-wave and oscillatory potentials (OP). Importantly, we observed severe degeneration of bipolar and ganglion cells. In contrast, outer retinal neurons (mainly photoreceptor cells) are mildly affected by colitis. Moreover, retinal inflammatory responses were significantly upregulated during colitis, including microglia activation, lymphocyte infiltration and cytokine/chemokine production. Notably, mucosal addressin cell adhesion molecule 1 (MAdCAM-1) was upregulated in retinal microvessels, especially the superficial and deep plexuses, and recruited gut-homing CD4 T cells to be co-localized with bipolar and ganglion cells during colitis. Expectedly, in vivo depletion of CD4 T cells or blockade of MAdCAM-1 greatly alleviated colitis-induced retinal inflammatory responses and neuron degeneration. Therefore, our data provide novel insight into the pathogenesis of IBD-associated retinal dysfunction, and targeted immune therapy directly against MAdCAM-1 might provide a novel approach in the management of eye EIM of IBD.
肠外表现（EIMs）的眼睛中发现的炎症性肠病（IBD）患者，但发病机制尚不清楚。为了探讨与 IBD 相关的视网膜功能障碍的发病机制，通过给予葡聚糖硫酸钠（DSS）诱导慢性结肠炎在小鼠。视网膜电图（ERG）进行评价视网膜功能。视网膜神经元变性通过免疫组织化学分析。结肠炎小鼠表现出 ERG 的 a-波和 b-波和振荡电位（OP）的幅度异常。重要的是，我们观察到双极细胞和节细胞严重退化。相比之下，外视网膜神经元（主要是光感受器细胞）结肠炎轻度影响。此外，视网膜炎症反应在结肠炎期间显著上调，包括小胶质细胞激活，淋巴细胞浸润和细胞因子/趋化因子的产生。值得注意的是，黏膜地址素细胞黏附分子 1（MAdCAM-1）在视网膜血管上调，尤其是浅层和深层丛，并招募肠道归巢 CD4 T 细胞在结肠炎期间与双极细胞和节细胞共定位。不出所料，体内耗尽 CD4 T 细胞或阻断 MAdCAM-1 大大减轻结肠炎诱导的视网膜炎症反应和神经元变性。因此，我们的数据为 IBD 相关的视网膜功能障碍的发病机制提供了新的见解，针对 MAdCAM-1 的靶向免疫治疗可能为 IBD 的眼部 EIM 的治疗提供新的方法。
