Measurement of trans-epithelial electrical resistance in perfusion: Potential application for in vitro ocular toxicity testing

An in vitro toxicity testing system that combines perfusion of a membrane- supported tissue model with measurement of trans-epithelial electrical resistance (TER) is described. The system is fully automated and allows for continuous TER measurements during exposure to a test agent. The utility of this system is demonstrated by the TER response of a tissue model composed of MDCK cells cultured on a cellulose ester filter to a series of nonionic surfactants (Triton X-100, Tween-20, Tween-80). The relative toxicities of the surfactants, as evaluated by the time needed to cause a 50% reduction in TER, are consistent with in vivo test results and with results from previous in vitro assays in static culture. The system can also be used to follow recovery of TER after a test agent has been removed from the perfusate. If the TER of the MDCK cell layer does not fall below a threshold value during surfactant exposure, the TER recovers at least part of the way to preexposure levels, beginning several hours after removal of the surfactant. A major benefit of this system is the increased amount of data obtained compared to traditional static assay systems. This may allow identification of parameters that correlate with different aspects of in vivo exposure.