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.

在 IBD 患者中发现了眼睛的肠外表现 (EIM)，但潜在的发病机制仍然未知。为了研究 IBD 相关视网膜功能障碍的发病机制，通过口服葡聚糖硫酸钠 (DSS) 在小鼠中诱发慢性结肠炎。进行视网膜电图 (ERG) 以评估视网膜功能。通过免疫组织化学分析视网膜神经元变性。结肠炎小鼠显示出异常的 ERG a-、b-波和振荡电位 (OP) 振幅。重要的是，我们观察到双极细胞和神经节细胞的严重退化。相反，外层视网膜神经元（主要是感光细胞）受结肠炎的影响较轻。此外，结肠炎期间视网膜炎症反应显着上调，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，粘膜寻址素细胞粘附分子 1 (MAdCAM-1) 在视网膜微血管中上调，尤其是浅表和深层神经丛，并募集肠道归巢 CD4⁺ T 细胞在结肠炎期间与双极细胞和神经节细胞共定位。^{不出所料，CD4 +} T 细胞的体内耗竭或 MAdCAM-1 的阻断大大减轻了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 相关视网膜功能障碍的发病机制提供了新的见解，直接针对 MAdCAM-1 的靶向免疫治疗可能为 IBD 眼 EIM 的管理提供一种新方法。