Differential effect of pH on the osmotic tolerance of rabbit corneal epithelium in tissue culture

The impact of pH on the osmotic tolerance of stratified corneal epithelium in vitro was determined after the instillation of a balanced salt solution and various pharmaceutical vehicles to determine the biocompatibility of the different formulations after 4-64 min exposures. Acute damage was assessed by the release of [³H]nucleotides and corresponding changes in tissue morphology. Protracted damage was evaluated by re-examining the morphology at 24 hr, along with determination of residual ³H release, tissue loss, and concomitant changes in protein synthesis. Our data indicated that an interaction between pH and osmolality was important for determining the biotolerance of balanced salt solutions, which may be explained by their chelating properties. In contrast, the impact of pH on the biocompatibility of unbuffered salines and phosphate-buffered vehicles was not quite as striking, which indicated these factors were not nearly as critical in these types of formulations. More conventional topical vehicles, by comparison, were much more toxic, which confirmed our suspicions that pH and osmolality are more critical factors in formulations containing chelating agents.