Effects of alpha-chymotrypsin on the outflow routes for aqueous humor.

The anterior chamber was perfused with alpha-chymotrypsin, 50 micrograms ml-1, in mock aqueous humor in cynomolgus monkeys. The enzyme caused a marked rise in outflow facility and had clear effects on the structure of the outflow routes for aqueous humor. The intertrabecular spaces in the iridocorneal chamber angle were wider than normal, the openings in the uveal and corneoscleral meshwork appeared enlarged, there was ballooning of the juxtacanalicular region and the inner wall of Schlemm's canal into the canal and also splitting of the inner wall of the canal. The trabecular cells appeared relaxed with most of the cell processes retracted, some broken. There were discontinuities in the cell membrane and blebs. Parts of the trabecular beams were denuded. Two days after the enzyme treatment the facility was in the normal range, no splits in the inner wall of Schlemm's canal we observed but many of the other changes in structure remained. The number of invaginations in the inner wall of Schlemm's canal was markedly reduced after 2-18 days. A second and third perfusion with alpha-chymotrypsin caused a rise in outflow facility similar to the first. Some morphological changes remained 163 days after enzyme treatment. Pilocarpine a few days after alpha-chymotrypsin treatment caused a marked increase in outflow facility. The results suggest that alpha-chymotrypsin affects the glycoproteins of the cell membrane and as a result causes disorganization of the cytoskeleton, loss of loose adhesions and breaks of cell processes. The rapid recovery of the resistance to outflow was probably due to healing of the splits in the inner wall of Schlemm's canal; a marked reduction in the number of cells with invaginations suggests that in addition there may have been a reduction in the number of transcellular pores in the inner wall of Schlemm's canal.