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Abstract #12436 Published in IGR 7-2
Reconstitution of trabecular meshwork GAGs: influence of hyaluronic acid and chondroitin sulfate on flow rates
Knepper PA; Fadel JR; Miller AM; Goossens W; Choi J; Nolan MJ; Whitmer SJournal of Glaucoma 2005; 14: 230-238
PURPOSE: This study was undertaken to determine whether the concentration of hyaluronic acid (HA) and of chondroitin sulfate (CS) occurring in the normal and the primary open-angle glaucoma (POAG) trabecular meshwork (TM) influences flow rates in vitro as a function of pressure. METHODS: We tested 100, 500, and 4000 kDa molecular weight HA, CS, reconstituted normal and POAG TM HA-CS and juxtacanalicular connective tissue (JCT) HA-CS in a micro test chamber to determine initial and steady-state flow rates. The resistance and permeability (Ko) were calculated; Linear Newtonian mechanics were used to determine the possible contributions of the hydrophobic interactions of HA. RESULTS: Initial flow rates increased in the pressure range of 5 to 20 mmHg for the three HA preparations and the flow rates declined in the pressure range of 20 to 40 mmHg. Flow rates of reconstituted normal TM and JCT were optimum at 10 mmHg and then declined with increasing pressure. Flow rates of reconstituted POAG TM and JCT were optimum only at 5 mmHg and then declined. The steady-state rate of POAG JCT HA-CS at 10 mmHg was slow: the transition time (i.e., the time required to start an increase in flow rate) was 29 hours and the lag time (i.e., the time required to obtain steady-state flow rate) was 17 hours. The maximum flow rate in POAG JCT HA-CS decreased by 37.2% from the normal JCT HA-CS. The calculated resistance of reconstituted POAG JCT HA-CS was approximately 18% of the total resistance of the human JCT compared with 10% in the normal JCT. CONCLUSIONS: Hyaluronic acid and CS contribute to flow resistance and influence flow rate in vitro. The influence of HA is particularly sensitive to an increase in the pressure gradient, which may be caused by unfolding of the hydrophobic interactions of HA polymers that further entangles the HA polymer. The POAG JCT HA-CS concentrations represent a significant factor in outflow resistance in POAG, particularly at higher pressures.
Dr. P.A. Knepper, Laboratory for Oculo-Cerebrospinal Investigation, Division of Neurosurgery, Children's Memorial Medical Center and Department of Ophthalmology, Northwestern University Medical School, Chicago, IL, USA. pknepper@northwestern.edu
Classification:
2.5.1 Trabecular meshwork (Part of: 2 Anatomical structures in glaucoma > 2.5 Meshwork)
3.10 Immunobiology (Part of: 3 Laboratory methods)