Platelet activating factor inhibits fluid transport by corneal endothelium.

PURPOSE: Given reports of corneal edema after endothelial exposure to platelet activating factor (PAF), the authors have investigated whether PAF can affect the function of corneal endothelium in vitro.

METHODS

The endothelial side of deepithelialized rabbit corneas was perfused with BSS+ and test agents: PAF, its inactive receptor ligand analog Lyso-PAF, and its antagonist BN52021. Stromal thickness was determined by specular microscopy. Translayer-specific electrical resistance (rho) was measured in cultured bovine corneal endothelial cells grown on permeable substrates at 36.5 degrees C.

RESULTS

Control corneas perfused with BSS+ or with BSS+ containing Lyso-PAF swelled at a very slow rate (6.2 +/- 0.1, and 7.9 +/- 0.2 microns/hour, respectively). Corneas exposed to PAF swelled appreciably faster and at rates that were a saturable function of PAF (K(m), 2.1 microM); maximal rates of swelling were < 20 microns/hour, indicating no appreciable damage to intercellular junctions. BN52021 prevented PAF-induced swelling (Ki, 1.1 microM). PAF led also to a decrease in rho (from 42.8 +/- 1.4 to 24.5 +/- 0.6 omega cm2 in 1 hour; 46.8 +/- 1.5 to 38.3 +/- 1.4 omega cm2 in control layers; and 43.0 +/- 1.2 to 30.8 +/- 1.6 omega cm2 in layers exposed to PAF+BN52021). Such rho changes are consistent with swelling of intercellular spaces.

CONCLUSIONS

Results suggest that PAF inhibits transendothelial fluid transport on binding to an endothelial cell receptor for it; continuous stimulation of a PAF-induced signaling cascade may lead to such inhibition. From these and other results, fluid transport might result from cascades activating sequentially basolateral and apical transporters or channels.