Lee Min Joung, Ko Ah Young, Ko Jung Hwa, Lee Hyun Ju, Kim Mee Kum, Wee Won Ryang, Khwarg Sang In, Oh Joo Youn
Department of Ophthalmology, Hallym University Sacred Heart Hospital, Anyang, Korea.
Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.
Mol Ther. 2015 Jan;23(1):139-46. doi: 10.1038/mt.2014.159. Epub 2014 Aug 25.
Dry eye syndrome (DES) is one of the most common ocular diseases affecting nearly 10% of the US population. Most of the currently available treatments are palliative, and few therapeutic agents target biological pathway of DES. Although DES is a multifactorial disease, it is well-known that inflammation in the ocular surface plays an important role in the pathogenesis of DES. Mesenchymal stem/stromal cells (MSCs) have been shown to repair tissues by modulating excessive immune responses in various diseases. Therefore, we here investigated the therapeutic potential of MSCs in a murine model of an inflammation-mediated dry eye that was induced by an intraorbital injection of concanavalin A. We found that a periorbital administration of MSCs reduced the infiltration of CD4(+) T cells and the levels of inflammatory cytokines in the intraorbital gland and ocular surface. Also, MSCs significantly increased aqueous tear production and the number of conjunctival goblet cells. Subsequently, corneal epithelial integrity was well-preserved by MSCs. Together, the results demonstrate that MSCs protect the ocular surface by suppressing inflammation in DES, and suggest that MSCs may offer a therapy for a number of ocular surface diseases where inflammation plays a key role.
干眼症(DES)是最常见的眼部疾病之一,影响着近10%的美国人口。目前大多数可用的治疗方法都是姑息性的,很少有治疗药物针对干眼症的生物学途径。尽管干眼症是一种多因素疾病,但众所周知,眼表炎症在干眼症的发病机制中起着重要作用。间充质干/基质细胞(MSCs)已被证明在各种疾病中通过调节过度的免疫反应来修复组织。因此,我们在此研究了间充质干细胞在由眶内注射伴刀豆球蛋白A诱导的炎症介导的干眼症小鼠模型中的治疗潜力。我们发现,眶周给予间充质干细胞可减少眶内腺体和眼表中CD4(+) T细胞的浸润以及炎性细胞因子的水平。此外,间充质干细胞显著增加泪液分泌量和结膜杯状细胞数量。随后,间充质干细胞很好地保护了角膜上皮的完整性。总之,结果表明间充质干细胞通过抑制干眼症中的炎症来保护眼表,并表明间充质干细胞可能为许多炎症起关键作用的眼表疾病提供一种治疗方法。