State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Department of Ophthalmology, University of Missouri, Columbia, MO, USA.
Ocul Surf. 2023 Jul;29:497-507. doi: 10.1016/j.jtos.2023.07.004. Epub 2023 Jul 6.
Meibomian glands (MGs) secrete lipid (meibum) onto the ocular surface to form the outermost layer of the tear film. Proper meibum secretion is essential for stabilizing the tear film, reducing aqueous tear evaporation, and maintaining the homeostasis of the ocular surface. Atrophy of MG as occurs with aging, leads to reduction of meibum secretion, loss of ocular surface homeostasis and evaporative dry eye disease (EDED). Since MGs are holocrine glands, secretion of meibum requires continuous self-renewal of lipid-secreting acinar meibocytes by stem/progenitor cells, whose proliferative potential is dramatically reduced with age leading to MG atrophy and an age-related meibomian gland dysfunction (ARMGD). Understanding the cellular and molecular mechanisms regulating meibocyte stem/progenitor cell maintenance and renewal may provide novel approaches to regenerating MG and treating EDED. Towards that end, recent label retaining cell and lineage-tracing experiments as well as knock-out transgenic mouse studies have begun to identify the location and identities of meibocyte progenitor cells and potential growth and transcription factors that may regulate meibocyte renewal. In addition, recent reports have shown that ARMGD may be reversed by novel therapeutics in mice. Herein, we discuss our current understanding of meibocyte stem/progenitor cells and the hunt for gland renewal.
睑板腺(MGs)分泌脂质(睑脂)到眼表面,形成泪膜的最外层。适当的睑脂分泌对于稳定泪膜、减少水样泪液蒸发和维持眼表面的内稳态至关重要。随着年龄的增长,MG 萎缩会导致睑脂分泌减少、眼表面内稳态丧失和蒸发性干眼症(EDED)。由于 MGs 是全浆分泌腺,因此睑脂的分泌需要由干细胞/祖细胞不断自我更新脂分泌的腺泡型 meibocytes,其增殖潜力随着年龄的增长而显著降低,导致 MG 萎缩和与年龄相关的睑板腺功能障碍(ARMGD)。了解调节 meibocyte 干细胞/祖细胞维持和更新的细胞和分子机制可能为再生 MG 和治疗 EDED 提供新的方法。为此,最近的标记保留细胞和谱系追踪实验以及敲除转基因小鼠研究开始确定 meibocyte 祖细胞的位置和身份,以及可能调节 meibocyte 更新的生长和转录因子。此外,最近的报告表明,新型治疗药物可能逆转 ARMGD。在此,我们讨论我们对 meibocyte 干细胞/祖细胞的现有理解和寻找腺体更新的方法。