Lacrimal Secretory Niche Remodeling in Dry Eye Disease: Single-Cell and Spatial Insights into Acinar Dysfunction

Reduced tear output can arise from altered neural regulation, impaired epithelial secretion, or loss of secretory tissue, with different implications for recovery. This focused narrative review integrates physiological, single-cell, spatial, organoid, and mechanistic studies identified through a structured PubMed search and targeted reference checking. We examine how remodeling of the lacrimal secretory niche affects acinar secretory competence, the capacity of viable acinar cells to convert stimulation into coordinated fluid, electrolyte, and protein secretion. Omics studies identify disease-associated expression patterns and candidate interactions, while selected perturbation studies link neural, inflammatory, and metabolic mechanisms to secretory dysfunction. We use residual functional reserve as a working concept for secretion that surviving tissue and its supporting niche can recruit through stimulation or relief of suppression. Potentially reversible functional suppression, persistent niche dysfunction, and structural failure describe overlapping constraints on secretion, not validated disease stages. These descriptions are distinct from the cellular, glandular, and lacrimal functional-unit levels at which outcomes are measured. The framework organizes questions about mechanism and recovery but does not establish a clinical treatment algorithm. Progress requires functional testing of candidate mechanisms and assessment of recovery at the level relevant to each claim.