Mount Sinai Researchers Identify Key Mechanisms Behind Age-Related Meibomian Gland Dysfunction

西奈山研究人员确定了与年龄相关的睑板腺功能障碍的关键机制

February 25, 2025

2025年2月25日

A research team led by Mount Sinai has identified stem cell populations and molecular mechanisms that contribute to age-related degeneration of the meibomian glands, which play a crucial role in maintaining eye health. Published in Nature Communications, these findings may pave the way for new therapeutic approaches to treat evaporative dry eye disease (EDED), a common condition in older adults..

由西奈山医院领导的一个研究团队已经确定了导致睑板腺与年龄相关退化的干细胞群和分子机制，睑板腺在维持眼部健康方面起着至关重要的作用。这些发表在《自然通讯》上的研究结果可能为治疗蒸发过性干眼病（EDED）开辟新的治疗途径，这是一种在老年人中常见的疾病。

Understanding the Role of Meibomian Glands in Eye Function

了解睑板腺在眼部功能中的作用

The meibomian glands, located along the eyelid margins, secrete lipid-rich meibum that prevents tear evaporation and protects the eye surface. Aging-related shrinkage of these glands, partially due to stem cell exhaustion, is closely linked to evaporative dry eye disease, leading to symptoms such as:.

位于眼睑边缘的睑板腺分泌富含脂质的睑脂，防止泪液蒸发并保护眼球表面。这些腺体随着年龄增长而萎缩，部分原因是干细胞耗竭，这与蒸发性干眼病密切相关，导致诸如以下症状：

• Swollen eyelids

• 眼睑肿胀

• Itchy, irritated eyes

• 眼睛发痒、受刺激

• Blurred vision

• 视力模糊

While current treatments like warm compresses, artificial tears, and thermal pulsation therapy offer symptom relief, they remain only partially effective.

虽然目前的治疗方法如热敷、人工泪液和热脉动治疗可以缓解症状，但它们的效果仍然有限。

Key Findings: The Role of Stem Cells and Signaling Pathways

关键发现：干细胞和信号通路的作用

The research team identified specific stem cell markers that maintain distinct regions of the meibomian glands and uncovered the hedgehog (Hh) signaling pathway as a critical regulator of stem cell proliferation and tissue regeneration.

研究团队确定了维持睑板腺不同区域的特定干细胞标志物，并揭示了刺猬（Hh）信号通路是干细胞增殖和组织再生的关键调节因子。

Notable Discoveries

重要发现

• Hh signaling is essential for meibomian gland function but declines with age.

• Hh信号传导对睑板腺功能至关重要，但会随着年龄增长而减弱。

• Reduced epidermal growth factor receptor (EGFR) signaling contributes to gland degeneration.

• 表皮生长因子受体（EGFR）信号传导减少会导致腺体退化。

• Aging glands show impaired innervation and a loss of collagen in fibroblast niches, further accelerating dysfunction.

• 衰老的腺体显示出神经支配受损和成纤维细胞巢中胶原蛋白的丧失，进一步加速功能障碍。

• Increased Hh signaling is a hallmark of human meibomian gland carcinoma, a rare and aggressive eyelid cancer.

• Hh信号增强是人类睑板腺癌的标志，这是一种罕见且侵袭性的眼睑癌症。

These findings suggest that targeting Hh and EGFR signaling to stimulate stem cell activity in the meibomian glands could be a potential therapeutic strategy for treating evaporative dry eye disease.

这些发现表明，针对Hh和EGFR信号通路来刺激睑板腺中的干细胞活性可能成为治疗蒸发性干眼病的潜在策略。

Expert Insights on the Study

专家对研究的见解

Dr. Sarah E. Millar, Senior Author and Dean for Basic Science at the Icahn School of Medicine at Mount Sinai, emphasized the significance of these findings:

西奈山伊坎医学院基础科学院长、资深作者莎拉·E·米勒博士强调了这些发现的重要性：

'Despite the prevalence of dry eye disease, the stem cells and molecular mechanisms that control homeostasis of the meibomian gland, and are impaired in aging, are poorly understood. We hope that our work will eventually result in new, more effective therapies for this very common condition.'

“尽管干眼病非常普遍，但控制睑板腺稳态并在衰老过程中受损的干细胞和分子机制仍知之甚少。我们希望我们的研究最终能为这一非常常见的疾病带来新的、更有效的治疗方法。”

Advanced Research Methods and Future Directions

高级研究方法与未来方向

To conduct this study, researchers used a mouse model system due to its structural and functional similarities to human meibomian glands. The team employed advanced techniques, including:

为了进行这项研究，研究人员使用了小鼠模型系统，因为它与人类睑板腺在结构和功能上具有相似性。团队采用了先进技 术，包括：

• Single-nuclear RNA sequencing

• 单核RNA测序

• In vivo lineage tracing

• 体内谱系追踪

• Ex vivo live imaging

• 离体活体成像

• Genetic gain- and loss-of-function studies

• 遗传获得和丧失功能研究

Additionally, gene expression was analyzed in normal human eyelid samples and human meibomian gland carcinoma.

此外，还在正常人眼睑样本和人睑板腺癌中分析了基因表达。

Next Steps in Research

研究的下一步

Dr. Millar and her team are now focusing on preclinical studies to evaluate whether small molecules that activate Hh and EGFR signaling can rescue age-related meibomian gland degeneration. This research involved collaborators from Johns Hopkins University, the University of Michigan, and the University of Pennsylvania..

米拉博士及其团队现在正专注于临床前研究，以评估激活Hh和EGFR信号的小分子是否能够挽救与年龄相关的眼睑腺退化。这项研究的合作伙伴来自约翰霍普金斯大学、密歇根大学和宾夕法尼亚大学。

As further studies advance, these findings could lead to innovative treatments that go beyond symptom management to address the root causes of evaporative dry eye disease.

随着研究的深入，这些发现可能会带来创新的治疗方法，超越症状管理，从根本上解决蒸发性干眼病的病因。

Reference:

参考：

Xuming Zhu et al, Identification of Meibomian gland stem cell populations and mechanisms of aging, Nature Communications (2025). DOI: 10.1038/s41467-025-56907-6

朱旭明等，《睑板腺干细胞群的鉴定与衰老机制》，《自然通讯》（2025）。DOI: 10.1038/s41467-025-56907-6