Figure 1. Role of barrier integrity in the regulation of stromal deturgescence.

Panel A: Fluid leakage into the stroma occurs through the paracellular pathway and is driven by a hydraulic gradient equivalent to the swelling pressure of the stroma (~ 50 mm Hg at normal stromal thickness). The paracellular pathway of the endothelium is characterized by a low transendothelial electrical resistance (TER < 30 Ω.cm²), and, hence, the endothelium forms a leaky epithelial interface at the stroma. The rate of leakage, however, is counter-balanced by the active fluid pump activity of the endothelium. Thus, the endothelial barrier integrity and fluid pump activity together maintain stromal deturgescence. Adapted from a previous review (Srinivas, 2010). Panel B: Panel B: When the barrier integrity breaks down, the pump mechanism cannot cope with the leak, and hence, stromal edema would be induced. Furthermore, when the tight junctions are abrogated, the fluid pump mechanism cannot continue since the local osmotic gradients generated by ion transport are dissipated by futile solute back-flux. The cytokines, such as TNF-α, that are implicated in allograft rejection may also directly reduce fluid transport activity by modulating the ion transport mechanisms.