May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
Application of Pore Theory to Macromolecular Diffusional Processes across Ageing Human Bruch's Membrane: Relevance to AMD.
Author Affiliations & Notes
  • A.A. Hussain
    Ophthalmology, KCL The Rayne Institute, London, United Kingdom
  • J. Marshall
    Ophthalmology, KCL The Rayne Institute, London, United Kingdom
  • Footnotes
    Commercial Relationships  A.A. Hussain, None; J. Marshall, None.
  • Footnotes
    Support  PPP Foundation, IRIS Fund
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 2290. doi:
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      A.A. Hussain, J. Marshall; Application of Pore Theory to Macromolecular Diffusional Processes across Ageing Human Bruch's Membrane: Relevance to AMD. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):2290.

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Abstract

Abstract: : Purpose: To quantify the diffusional status of macromolecular transport processes across Bruch’s membrane in both normal and AMD–affected donors. To assess the applicability of the classical pore theory of restricted diffusion through cylindrical channels to the complex pentalaminated structure of Bruch’s membrane and thereby characterise the dynamics of the transport pathway. Methods: All studies utilised an isolated Bruch’s–choroid complex [17 control (4–92years) and 4 AMD (76–95 years) donors] held in standard Ussing–type chambers. The size exclusion limit (providing a value of pore radii) was measured by quantifying the rate of diffusion of a series of quasi–spherical molecular probes typified by the FITC–dextrans (4.4–150kDa). The diffusional status of Bruch’s was assessed by measuring the rate of diffusion of a 21.2 kDa dextran, a species known to be smaller than the size exclusion limit of the membrane. Results: The size exclusion radii of Bruch’s membrane from macular and peripheral regions were 6.17nm (range 5.76–6.54nm) and 6.35nm (range 6.01–6.66nm) respectively. These limits were unaltered by the ageing process. In the normal population, diffusional transport of the 21.2 kDa dextran declined linearly with age at both macular and peripheral locations (p<0.001). Thus in the elderly (80+ years), diffusion rates in the macular and peripheral regions were 19 and 50% of those at birth respectively. In comparison with age–matched controls, diffusion rates in samples from AMD donors were significantly lower (p<0.001). Predictions from the pore theory of restricted diffusion were in agreement with experimental data for molecular species equal to or bigger than 50% of the exclusion radii. Smaller molecular species showed considerable deviation with diffusion rates well below prediction. Conclusions: Although the size exclusion limit of Bruch’s membrane remains unaltered, ageing causes a significant decline in the rate of diffusion of macromolecules at both macular and peripheral locations. In keeping with the advanced ageing hypothesis for AMD, diffusion through Bruch’s membrane was considerably reduced. The impact of these changes on the pathophysiology of AMD will be discussed together with the usefulness of pore theory in understanding the molecular mechanisms of the ageing process.

Keywords: age–related macular degeneration • Bruch's membrane • aging 
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