SLC6A6-Mediated Taurine Uptake Sustains Corneal Epithelial Stem/Progenitor Cell Function to Counteract Age-Related Dysfunction.

<h4>Purpose</h4>This study aimed to elucidate the role of SLC6A6-mediated taurine transport in maintaining corneal limbal stem/progenitor cell (LSPC) function and its implications for age-associated corneal wound healing.<h4>Methods</h4>Corneal amino acid profiles from C57BL/6J mice were analyzed via liquid chromatography-tandem mass spectrometry (LC-MS/MS). SLC6A6 expression patterns were mapped using single-cell RNA sequencing, quantitative PCR, and immunofluorescence. Pharmacological inhibition of SLC6A6 with guanidinoethyl sulfonate (GES) was applied in corneal wound healing models and murine corneal epithelial stem/progenitor (TKE2) cells. Transcriptomic profiling, RNA/protein analyses, and functional assays were performed in GES-treated TKE2 cells. Aged mice with corneal epithelium scraping received topical taurine supplementation (25 mg/mL, 5 times/day), and the corneas were collected for immunofluorescence staining. Moreover, TKE2 cells were treated with GES along with the Notch1 agonist valproic acid (VPA), or they were treated with taurine along with the Notch1 inhibitor GSI-IX (DAPT).<h4>Results</h4>The cornea exhibited high taurine concentrations, with its transporter SLC6A6 predominantly localized in LSPCs (limbal stem cells, transient amplifying cells, and basal cells) and displaying age-dependent expression patterns. SLC6A6 inhibition delayed corneal wound healing, triggered senescence(definition) pathway activation and pluripotency suppression, and downregulated stemness markers (BCAM, p63, KRT14, Wnt4) and proliferative markers (Ki67), which recapitulated key features of corneal aging. This functional decline was reversed through topical taurine supplementation. Moreover, VPA effectively reversed the inhibitory effect of GES, whereas DAPT attenuated the effect of taurine, indicating involvement of the Notch1 signaling pathway in taurine-induced LSPC maintenance.<h4>Conclusions</h4>SLC6A6-driven taurine uptake critically regulates LSPC homeostasis, presenting a therapeutic strategy for age-related corneal disorders.