Department of Ophthalmology and Visual Science, Catholic Institute of Visual Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Department of Biochemical Engineering, Seoil University, Seoul 06591, Republic of Korea.
Int J Mol Sci. 2023 Jan 5;24(2):1039. doi: 10.3390/ijms24021039.
Sjögren's syndrome (SS) is a systemic autoimmune disease delineated by chronic lymphocytic infiltrates into the lacrimal or salivary glands, leading to severe dry eye and dry mouth. Mesenchymal stem cells have been shown to be effective in treating numerous autoimmune diseases. This study aimed to illustrate the effects of mesenchymal stem cells on the attenuation of dry eyes (DE) through the inhibition of autophagy markers in a SS mouse model. NOD/ShiLtJ female mice with developed DE were treated with either subconjunctival or lacrimal gland injections of hMSCs (Catholic MASTER Cells). After maintenance for 14 days, clinical DE markers such as tear secretion and corneal staining were observed, as well as goblet cell counts in the conjunctiva, infiltration of inflammatory foci, B and T cells, and autophagy markers in the lacrimal glands. Proinflammatory cytokine expressions of the cornea and conjunctiva, as well as the lacrimal glands, were examined. Clinical markers, such as tear secretion and corneal stain scores, goblet cell counts in the conjunctiva, and foci infiltrations in the lacrimal glands were attenuated in mice treated with subconjunctival or lacrimal gland injections of hMSCs compared to the PBS-treated control group. B cell marker B220 decreased in the lacrimal glands of hMSCs-treated mice, as well as reduced proinflammatory cytokine expressions in the lacrimal glands and cornea. Notably, expression of autophagy markers ATG5 and LC3B-II, as well as HIF-1α and mTOR which play roles in the pathways of autophagy modulation, were shown to be attenuated in the lacrimal glands of hMSCs-treated mice compared to the PBS-treated control mice. Treatment with hMSCs by lacrimal gland or subconjunctival injection demonstrated the alleviation of DE through the repression of autophagy markers, suggesting the therapeutic potentials of hMSCs in a SS mouse model.
干燥综合征（SS）是一种系统性自身免疫性疾病，其特征为慢性淋巴细胞浸润泪腺或唾液腺，导致严重的干眼和口干。间充质干细胞已被证明在治疗多种自身免疫性疾病方面有效。本研究旨在通过抑制 SS 小鼠模型中自噬标志物来阐明间充质干细胞对干眼（DE）的缓解作用。已经发展为 DE 的 NOD/ShiLtJ 雌性小鼠用结膜下或泪腺注射 hMSC（天主教 MASTER 细胞）进行治疗。维持 14 天后，观察临床 DE 标志物，如泪液分泌和角膜染色，以及结膜中的杯状细胞计数、炎症灶浸润、B 和 T 细胞以及泪腺中的自噬标志物。还检查了角膜和结膜以及泪腺的促炎细胞因子表达。与 PBS 处理的对照组相比，结膜下或泪腺注射 hMSC 治疗的小鼠的临床标志物，如泪液分泌和角膜染色评分、结膜中的杯状细胞计数以及泪腺中的灶浸润减少。B 细胞标志物 B220 在 hMSC 治疗的小鼠的泪腺中减少，并且泪腺和角膜中的促炎细胞因子表达减少。值得注意的是，与 PBS 处理的对照组相比，hMSC 治疗的小鼠的泪腺中自噬标志物 ATG5 和 LC3B-II 以及在自噬调节途径中起作用的 HIF-1α 和 mTOR 的表达减弱。泪腺或结膜下注射 hMSC 治疗通过抑制自噬标志物显示出对 DE 的缓解作用，表明 hMSC 在 SS 小鼠模型中的治疗潜力。
