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 whethe r 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 L yso-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 p ermeable substrates at 36.5 degrees C. Results, Control corneas perfus ed with BSS+ or with BSS+ containing Lyso-PAF swelled at a very slow r ate (6.2 +/- 0.1, and 7.9 +/- 0.2 mu m/hour, respectively). Corneas ex posed to PAF swelled appreciably faster and at rates that were a satur able function of PAF (K-m, 2.1 mu M); maximal rates of swelling were < 20 mu m/hour, indicating no appreciable damage to intercellular juncti ons. BN52021 prevented PAF-induced swelling (K-l, 1.1 mu M). PAF led a lso to a decrease in rho (from 42.8 +/- 1.4 to 24.5 +/- 0.6 Omega cm(2 ) in I hour; 46.8 +/- 1.5 to 38.3 +/- 1.4 Omega cm(2) in control layer s; and 43.0 +/- 1.2 to 30.8 +/- 1.6 Omega cm(2) in layers exposed to P AF + BN52021). Such rho changes are consistent with swelling of interc ellular spaces. Conclusions, Results suggest that PAF inhibits transen dothelial fluid transport on binding to an endothelial cell receptor f or it; continuous stimulation of a PAF-induced signaling cascade may l ead to such inhibition. From these and other results, fluid transport might result from cascades activating sequentially basolateral and api cal transporters or channels.