WNT Mimetic-Induced Lacrimal Gland Regeneration

Although tear replacement and anti-inflammatory treatments have been thoroughly investigated, 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. Transcriptional and cellular changes were investigated using single cell sequencing. 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. We demonstrate a role for WNT signaling in acinar cell proliferation, and scRNA-seq revealed that the WNT mimetic promotes pathway activation and proliferation in injury-induced states. Our findings extend the potential for WNT pathway activation via a ligand mimetic platform to lacrimal gland regeneration. Lacrimal gland duct ligation was used to cause damage to the lacrimal gland. After three days, the ligation was removed and animals were treated with either a control treatment or a WNT mimetic. At the indicated endpoint, the lacrimal gland was removed and dissociated. Viable cells were selected by DAPI exclusion and FACS purified. 10x Genomics 3' v3.1 chemistry was used for scRNA-seq, and tissue was collected from uninjured animals, day 1, day 5, and day 7. Our attempt to collect day 3 failed due to a clog in the cell capture device.