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W. Goossens, A.M. Miller, J. Choi, E.R. Doherty, S. Whitmer, P.A. Knepper; Percolation Test of Trabecular Meshwork Glycosaminoglycans . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1161.
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Purpose: Glycosaminoglycans (GAGs) influence extracellular fluid movement in connective tissue matrices such as the trabecular meshwork (TM). In primary open-angle glaucoma (POAG), the TM concentration of hyaluronic acid (HA) is decreased and chondroitin sulfate (CS) is increased, especially within the juxtacanalicular connective tissue (JCT). This study was designed to determine the influence of normal and POAG JCT concentrations of HA and CS on steady state flow rates. Methods: Highly purified preparations of 500 kDa molecular weight HA in a concentration of 0.1 mg/ml, reconstituted normal JCT containing HA in a concentration of 0.780 mg/ml and CS in a concentration of 0.818 mg/ml, and reconstituted POAG JCT containing HA in a concentration of 0.057 mg/ml and CS in a concentration of 1.349 mg/ml were tested in a micro-test chamber, and initial and steady state flow rates were measured as a function of pressure at 10, 20, and 40 mmHg. The permeability (K) was calculated for initial and steady state conditions. Results: The contribution of normal and POAG JCT HA-CS concentrations on the initial flow rates were pressure-dependent. A characteristic pattern of flow rate change for all preparations was a sigmoidal curve: a low plateau flow rate, a gradual increase in flow rate, and a steady-state flow rate. Steady state conditions were reached in a time-dependent manner, which revealed that reconstituted JCT in POAG requires a much greater period of time to obtain the steady state condition than normal. POAG steady state at 10 mmHg was obtained after 46 hours compared with 25 hours for normal, and at 40 mmHg, POAG steady state was obtained after 121 hours compared to 77 hours for normal. The steady state flow rate at 10 mmHg for POAG was 7.6 µl/min compared with a normal flow rate of 12.2 µl/min, a 38% reduction, whereas the steady state flow rate at 40 mmHg for POAG was 28.0 µl/min compared with a normal flow rate of 46.1 µl/min, a 40% reduction. Conclusions: The filtration capacity of the POAG reconstituted TM GAGs is compromised. Although the steady state permeabilities of HA, normal GAGs, and POAG GAGs were similar, the equilibration time for steady state was prolonged for POAG, and the flow rate was remarkably reduced in POAG.
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