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Abstract #6516 Published in IGR 3-2
Cationic ferritin changes outflow facility in human eyes whereas anionic ferritin does not
Ethier CR; Chan DWHInvestigative Ophthalmology and Visual Science 2001; 42: 1795-1802
PURPOSE: To determine the effect of charge moieties within the outflow pathway on aqueous outflow facility in human eyes. METHODS: After baseline facility measurement in human eyebank eyes (n = 10 pairs), one eye of each pair received anterior chamber exchange and continued perfusion with medium containing 10 mg/ml cationic ferritin. Contralateral eyes were treated in a similar manner with anionic ferritin (10.0 or 102 mg/ml). Eyes were fixed by anterior chamber exchange and perfusion with universal fixative at 8 mmHg (corresponding to a physiological pressure of 15 mmHg in vivo) and examined by transmission electron microscopy (TEM). In a second series of human eyes (n = 8 pairs), facility was measured before and after anterior chamber exchange, with a solution containing 0.1 U/ml neuraminidase. RESULTS: Perfusion of eyes with anionic ferritin at either 10.0 or 102 mg/ml caused a negligible 2% increase in facility, whereas cationic ferritin perfusion reduced facility by 66% (p < 0.00001). Perfusion with fixative reduced facility by approximately 60% in both cationic and anionic ferritin-perfused eyes, relative to facilities after perfusion with ferritin. TEM showed that the distribution of ferritin was segmentally variable. Cationic ferritin consistently labelled the luminal surface of the inner wall of Schlemm's canal, and variably labelled the juxtacanalicular 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, cationic ferritin was seen to accumulate at the intercellular margins of the inner wall. Neuraminidase perfusion had no significant effect on outflow facility. CONCLUSIONS: Cationic ferritin reduces outflow facility, presumably by binding to negatively charged sites in the outflow pathway. A possible mechanism 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 facility. These data indicate that positively-charged molecular, especially if they can interact with inner wall pores, have the potential to markedly alter outflow facility.
Dr C.R. Ethier, Department of Mechanical and Industrial Engineering, 5 King's College Road, University of Toronto, Toronto, Ontario M5S 3G8, Canada. ethier@mie.utoronto.ca
Classification:
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
