Regulation of corneal stromal cell behavior by modulating curvature using a hydraulically-controlled organ chip array

Cornea exhibits distinct curvature-dependent mechanical environments that influence stromal cell phenotype and extracellular matrix remodeling. In this study, we employed a hydraulically-controlled cornea-on-a-chip platform to systematically vary curvature and examine transcriptional and phenotypic responses of human corneal keratocytes. RNA sequencing revealed differential expression profiles associated with curvature states that mimic pathological conditions such as cornea plana and keratoconus. Curvature-dependent regulation of extracellular matrix genes, cytoskeletal organization, and signaling pathways was validated with qPCR and immunostaining. These findings provide transcriptomic insights into how corneal tissue geometry contributes to disease progression and may inform future therapeutic strategies for corneal ectatic disorders. RNA-seq profiling of primary human corneal keratocytes cultured on curvature-controlled chips under four conditions: flat (control), low curvature, medium curvature, and high curvature. Each sample was collected at Day 9 after applying curvature for 6 days.