Aging is a well-established risk factor for meibomian gland dysfunction (MGD). We previously reported an accelerated cellular senescence phenomenon in the lacrimal glands of a murine model of chronic graft-versus-host disease (cGVHD). Herein, we aimed to elucidate the relationship between cellular senescence and MGD in cGVHD mice, utilizing the senolytic agent ABT-263. A cGVHD mouse model was established through allogeneic bone marrow transplantation (BMT) from B10.D2 to BALB/c mice. Subsequently, cGVHD mice were treated with either ABT-263 or vehicle. The eyelids of recipients were analyzed at 4-week intervals post-BMT in both groups. Meibomian gland (MG) area was significantly smaller in cGVHD mice than in syngeneic control mice. ABT-263-treated mice retained a significantly larger MG area than their vehicle-treated counterparts. Pathological and immunohistochemical examinations revealed significant reductions in eyelid tissue inflammation and pathological fibrosis in the ABT-263 group compared to that in the vehicle-treated group. Additionally, expression of DNA damage markers, senescent cell markers, and senescence-associated secretory phenotype (SASP) factors was elevated in the eyelids of cGVHD mice compared with that in syngeneic mice. The expression of these cellular senescence-associated molecules was considerably suppressed in ABT-263-treated eyelids compared to that in vehicle-treated ones. Cellular senescence, along with expression of SASP factors, exhibited increased activity in the eyelids, particularly in the MGs of cGVHD mice. ABT-263 mitigated the severity of MGD. These findings highlight the potential of targeting cellular senescence as an effective approach for MGD treatment in cGVHD.

中文翻译：

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细胞衰老促进慢性移植物抗宿主病小鼠模型睑板腺功能障碍

衰老是睑板腺功能障碍 (MGD) 的一个公认的危险因素。我们之前报道了慢性移植物抗宿主病（cGVHD）小鼠模型泪腺中细胞加速衰老的现象。在此，我们旨在利用衰老抑制剂 ABT-263 阐明 cGVHD 小鼠细胞衰老与 MGD 之间的关系。通过B10.D2小鼠同种异体骨髓移植(BMT)至BALB/c小鼠建立cGVHD小鼠模型。随后，cGVHD 小鼠接受 ABT-263 或载体治疗。 BMT 后每隔 4 周对两组受者的眼睑进行分析。 cGVHD 小鼠的睑板腺 (MG) 面积明显小于同系对照小鼠。 ABT-263 处理的小鼠比媒介物处理的小鼠保留了显着更大的 MG 面积。病理学和免疫组织化学检查显示，与媒介物治疗组相比，ABT-263 组眼睑组织炎症和病理性纤维化显着减少。此外，与同系小鼠相比，cGVHD 小鼠眼睑中 DNA 损伤标记物、衰老细胞标记物和衰老相关分泌表型 (SASP) 因子的表达升高。与媒介物处理的眼睑相比，这些细胞衰老相关分子的表达在 ABT-263 处理的眼睑中显着受到抑制。细胞衰老以及 SASP 因子的表达表现出眼睑活性增加，特别是在 cGVHD 小鼠的 MG 中。 ABT-263 减轻了 MGD 的严重程度。这些发现凸显了针对细胞衰老作为治疗 cGVHD 的 MGD 有效方法的潜力。