WNT Mimetic-Induced Lacrimal Gland Regeneration Reverses Aqueous Tear Deficiency

作者：Huy Nguyen, Russell B. Fletcher, Tom Lopez, Elizabeth Whisler, Kelsey Ronarda Logas, Navrose Dhaliwal, Timothy Suen, Mengrui Zhang, Archana Dilip, Tom Z. Yuan, Hayoung Go, Jay Ye, Parthasarathy Sampathkumar, Nick Suen, Hui Chen, Wen‐Chen Yeh, Yang Li, Yorick Post · 发表于：Translational Vision Science & Technology · 年份：2025 · DOI：10.1167/tvst.14.6.19 · 被引用次数：4 · 研究领域：Ocular Surface and Contact Lens、Proteoglycans and glycosaminoglycans research、Salivary Gland Disorders and Functions

Purpose: Dry eye disease is characterized by abnormal tear film composition and inflammation. Disruptions in the presence or secretory function of acinar cells can result in dry eye, leading to discomfort, damage, and vision loss. Although tear replacement and anti-inflammatory treatments have been investigated thoroughly, a method to induce epithelial restoration is lacking. Here, we asked whether WNT signaling activation via an antibody-based WNT mimetic platform might activate lacrimal gland acinar cells and restore tear secretion. Methods: Primary murine lacrimal gland cells were used to establish three-dimensional acinar cell organoids. Dry eye disease was modeled in mice using a lacrimal gland excretory duct ligation. Transcriptional and cellular changes were investigated using single-cell sequencing. Results: Frizzled and LRP5/6 receptors, which are essential for WNT signal transduction, are expressed in glandular acinar cells in vivo. We showed that murine acinar cells can be expanded as organoids by using WNT signaling activation. Here, we demonstrate that WNT signaling is an essential factor for acinar cell proliferation ex vivo. In a mouse model of dry eye disease, and intra-lacrimal gland treatment with a WNT mimetic targeting FZD1, 2, and 7 reversed aqueous tear deficiency. After excretory duct ligation damage, WNT mimetic treatment promoted acinar cell restoration and increased detectable tear volume production. Conclusions: We demonstrate a role for WNT signali...