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

Abstract 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. Using adaptive mesh refinement direct numerical simulation (AMR-DNS), we quantitatively reproduced the spiral stromal flow patterns reported by Inoue et al., supporting the physiological plausibility of HEZ + Marangoni-driven convection. Furthermore, Park et al. (Nature Chemistry, 2023) experimentally demonstrated that ionic concentration gradients induce strong solutal Marangoni forces, reinforcing our proposed mechanism. We also introduce an entropy balance equation (ΔS_in − ΔS_out ≤ 0) as a unifying principle linking stromal metabolism, endothelial transport, and thermodynamic stability. Disruption of this balance may underlie various corneal pathologies, including keratoconus, edema, and graft rejection. Finally, we propose OCT-derived biomarkers and an endothelial HEZ transport index (EHTI) as potential diagnostic tools to quantify local entropy dissipation and assess disease risk. This interdisciplinary framework bridges experimental findings, computational modeling, and clinical applications, offering novel insights into corneal physiology and pathology.