High Entropy-Production Zone (HEZ) and Marangoni Effect-Driven Convection: A Hypothesis for Corneal Stromal Dynamics

The cornea is a metabolically active, transparent tissue considered to be a nonequilibrium open biological system that must continuously dissipate internally generated entropy to maintain its highly ordered structure and optical transparency. Here, we present a biophysical modeling framework integrating thermodynamics, fluid dynamics, and computational simulations to explain corneal homeostasis. We propose the existence of a functional High Entropy-Production Zone (HEZ) within the anterior stroma, where sustained metabolic activity establishes persistent thermal and solute gradients. These gradients are hypothesized to drive Marangoni effects, particularly solutal Marangoni forces, promoting efficient entropy dissipation toward the anterior chamber. Based on thermodynamic principles, we first hypothesized the existence of a High Entropy-Production Zone (HEZ) within the anterior stroma, predicting that Marangoni-driven convection would emerge. Using AMR-DNS-based conceptual simulations, we then tested these predictions against the experimental benchmark of Inoue et al., finding strong concordance. These results support the physiological plausibility of HEZ and Marangoni-driven convection and are thought to indicate the mechanisms of entropy dissipation and the dual-engine hypothesis within corneal tissue. In this study, we introduce the entropy balance equation (ΔS in – ΔS out ≤ 0) as a fundamental principle for integratively understanding stromal metabolism, endothelial transport, and thermodynamic stability. Disruption of this entropy balance may underlie various corneal pathologies, including keratoconus, corneal edema, and graft rejection. Furthermore, this framework represents an interdisciplinary approach that bridges experimental findings, computational modeling, and clinical applications, providing new perspectives on corneal physiology and disease mechanisms.