Cationic ferritin changes outflow facility in human eyes whereas anionic ferritin does not

PURPOSE. TO determine the effect of charged moieties within the outflow pat hway on aqueous outflow facility in human eyes. METHODS. After baseline facility measurement in human eye bank eyes (n = 10 pairs), one eye of each pair received anterior chamber exchange and contin ued perfusion with medium containing 10 mg/ml cationic ferritin. Contralate ral eyes were treated in a similar manner with anionic ferritin (10.0 or 10 2 mg/ml). Eyes were fixed by anterior chamber exchange and perfusion with u niversal fixative at 8 mm Hg (corresponding to a physiologic pressure of 15 mm Hg in vivo) and examined bl transmission electron microscopy. In a seco nd series of human eyes (n = 8 pairs), facility was measured before and aft er anterior chamber exchange, with a solution containing 0.1 U/ml neuramini dase. RESULTS. Perfusion of eyes with anionic ferritin at either 10.0 or 102 mg/m l caused a negligible 2% increase in facility, whereas cationic ferritin pe rfusion reduced facility by 66% (P < 0.00001). Perfusion with fixative redu ced facility by approximate 60%, in both cationic and anionic ferritin-perf used eyes, relative to facilities after perfusion with ferritin. Transmissi on electron microscopy showed that the distribution of ferritin was segment ally variable. Cationic ferritin consistently labeled the luminal surface o f the inner wall of Schlemm's canal, and variably labeled the juxtacanalicu lar connective tissue (JCT) and trabecular beam surfaces. Anionic ferritin was more prominent in the JCT and intertrabecular spaces and less so on the luminal surface of Schlemm's canal. By scanning electron microscopy, catio nic ferritin was seen to accumulate at intercellular margins of the inner w all. Neuraminidase perfusion had no significant effect on outflow facility. CONCLUSIONS. Cationic ferritin reduces outflow facility, presumably by bind ing to negatively charged sites in the outflow pathway. A possible mechanis m is partial or complete blockage of intercellular clefts in the inner wall of Schlemm's canal by the ferritin that accumulates on the luminal surface of the inner wall. Although they are possible targets for ferritin binding , sialyl residues themselves seem to have little direct effect on outflow f acility. Our data indicate that positively charged molecules, especially if they can interact with inner wall pores, have the potential to markedly al ter outflow facility.