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W.J. McCarty, M. Johnson; A Matrigel Model of Bruch's Membrane: Effects of Lipids on Hydraulic Conductivity . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1394.
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© ARVO (1962-2015); The Authors (2016-present)
Age–related macular degeneration (AMD) is characterized by lipid accumulation in Bruch’s membrane. We determined the effect of lipoprotein accumulation on the hydraulic conductivity of a Matrigel model of Bruch’s membrane. As a control, we compared this with the effects of microsphere accumulation in the same model.
Hydraulic conductivity (HC) data were collected by mixing low density lipoproteins or latex microspheres (5% by weight) into liquid solutions of Matrigel basement membrane matrix (10.5 mg/ml) at 4°C. This mixture was injected into a modified Ussing chamber supported by 50 nm pore–size filters, allowed to gel at 25°C for 30 min, and connected to a perfusion system that measured pressure drop and flow rates. The experimental HC values of the gels with lipids or latex were compared to predictions using Brinkman’s equation.
The hydraulic conductivity values of Matrigel with the added latex spheres decreased to 75% of the baseline results over nearly the entire pressure range of 10–100 mmHg. This result matches well with the predicted value based on Brinkman’s equation. When lipids were added, however, the HC values decreased to 40% of the baseline, nearly twice as much change as with the latex spheres.
There is a significant decrease in permeability with the addition of solids in extracellular matrix, even at solid fractions as low as 5%. The decrease was nearly twice as large for low density lipoproteins as compared with latex spheres. The exact reason for this has not been uncovered, but the finding suggests lipid accumulation is more damaging to extracellular membrane transport characteristics than flow resistance models will predict.
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