Commentary: Toward a global atlas of ocular surface biology: Rationale, design, and clinical applications

The ocular surface-comprising the cornea, conjunctiva, and tear film apparatus-acts as a dynamic barrier to the external environment and is a leading site of vision-threatening disorders such as dry eye disease, keratoconus, and corneal graft rejection. Recent advances in single-cell and spatial omics now enable systematic, high-resolution profiling of this complex tissue. We propose the Atlas of Ocular Surface Biology, a global initiative modeled on the Human Cell Atlas and BRAIN Initiative, to comprehensively map all major ocular surface compartments-across health and disease-through integrative multi-omics including sc/snRNA-seq, ATAC-seq, spatial transcriptomics, and tear-fluid proteomics/metabolomics. The revised framework provides a phased clinical translation roadmap with explicit decision gates and two first-deployed use cases: (i) noninvasive tear-based endotyping of dry eye disease for mechanism-guided therapy allocation, and (ii) preclinical monitoring of corneal transplant rejection through a longitudinal tear-based Rejection Risk Score. Beyond pan-ocular efforts, the atlas will capture microenvironmental dynamics-including limbal stem-cell niches, goblet-cell gradients, tear film-microorganism interactions, environmental exposure responses (pollutants, humidity, contact lens wear), and immune surveillance at a mucosal barrier. We benchmark mainstream data-integration tools (e.g., Seurat, Harmony, MultiVI, cell2location, SpaIM, DIABLO, MOFA+) and specify quantitative guardrails (kBET, iLISI, cLISI/ARI, rare-cell recall) to ensure reproducibility, biological-signal preservation, and readiness for cross-site clinical deployment. Governed by an international, HCA-aligned consortium with open-science and ethical data-sharing principles, the Atlas will function as both a continuously evolving reference and a translational toolkit, enabling AI-guided diagnostics, molecular stratification, and personalized interventions in precision ophthalmology. This resource is intended to support global collaboration in vision science and to inform future mucosal-surface atlas efforts.