Ethacrynic acid effects on inner wall pores in living monkeys

PURPOSE. The influence of the inner wall of Schlemm's canal on aqueous outf low facility remains poorly understood. We examined the relationship betwee n inner wall pore characteristics and outflow facility in living primate ey es in which facility had been pharmacologically increased by ethacrynic aci d (ECA) infusion and in contralateral control eyes. METHODS. Outflow facility (two-level constant pressure perfusion) was measu red in eight pairs of living monkey eyes before and after administration of a bolus dose of either 0.125 mM ECA or vehicle. After exsanguination, eyes were fixed in situ under constant-pressure conditions (mean fixation press ure approximate to 19 mm Hg). The density and diameter of inner wall pores and the number and area of platelet aggregates on the inner wall of Schlemm 's canal were measured by scanning electron microscopy. RESULTS. In EGA-treated eyes, outflow facility increased 63% (P < 0.0001), intracellular pore density decreased 46% (P = 0.0094), intracellular pore s ize increased 27% (P = 0.049), platelet aggregate density increased 158% (P < 0.0001), and area covered by platelets increased 210% (P = 0.012) relati ve to contralateral controls. Although the average density and size of inte rcellular pores were essentially unaffected by EGA, an increased density of large (greater than or equal to 1.90 mu m) intercellular pores was seen in EGA-treated eyes. The density of intracellular pores increased with the du ration of fixative perfusion. Other than a weak negative correlation betwee n outflow facility and intracellular pore density in EGA-treated eyes (P = 0.052), facility was not correlated with inner wall pore features. CONCLUSIONS. OUT data are most consistent with a scenario in which ECA prom otes formation of large intercellular pores in the inner wall of Schlemm's canal, which are then masked by platelet aggregates. Masking of intercellul ar pores, combined with fixation-induced alteration of inner wall pore dens ity, greatly complicates attempts to relate facility to inner wall structur e and suggests that in vivo pore density is smaller than in fixed tissue. A dditionally, facility-influencing effects of EGA on the juxtacanalicular ti ssue cannot be excluded.