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S Whitmer, AM Miller, W Goossens, J Choi, PA Knepper; POAG Trabecular Meshwork Glycosaminoglycans: Influence of Hyaluronic Acid and Chondroitin Sulfate on Initial Flow Rates . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1030.
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Purpose: In primary open-angle glaucoma (POAG), the trabecular meshwork (TM) concentration of hyaluronic acid (HA) is decreased and chondroitin sulfate (CS) is increased. This study was designed to determine the influence of normal and POAG TM concentration of HA and CS on flow rates. Methods: Highly purified preparations of 100, 500, and 4,000 kDa molecular weight HA--in concentrations of 0.1, 0.3, and 1.0 mg/ml--Viscoat®, CS, and reconstituted normal and POAG HA-CS concentrations were tested in a micro-test chamber, and flow rates as a function of pressure were measured. The resistance and permeability (K) were calculated; linear Newtonian mechanics were used to determine the possible contributions of the hydrophobic interactions and entanglement of HA. Results: The contribution of TM HA-CS concentration on outflow resistance was pressure-dependent: less than 1% at 5 mmHg and greater than 10% at 40 mmHg in POAG. Flow rates increased in the pressure range 5 to 10 mmHg for the three HA preparations; flow rates decreased as a function of pressure for CS. Flow rates of normal TM were optimum at 10 mmHg (21.4 µl/min) and then declined. Flow rates of reconstituted POAG TM were optimum only at 5 mmHg (10.5 µl/min) and then declined. The resistance of the reconstituted POAG at 10 mmHg was 2.7 times greater (P< 0.001) than that of normal. Conclusion: HA and CS contribute to flow rate in vitro. The influence of HA is particularly sensitive to pressure, presumably as a result of disruption in and within the hydrophobic interactions of HA polymers, which further entangles the HA polymer. As pressure gradient is increased, the contribution of HA and CS to resistance increases 10-fold in POAG and thus HA and CS concentrations are a factor in aqueous outflow resistance in POAG.
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