May 2005
Volume 46, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2005
Potential Usefulness of AGE Cross–Link Breakers for Modulating the Progression of AMD
Author Affiliations & Notes
  • A.A. Hussain
    Ophthalmology, KCL The Rayne Institute, London, United Kingdom
  • W.H. Chan
    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; W.H. Chan, None; J. Marshall, None.
  • Footnotes
    Support  Iris Fund UK
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 1211. doi:
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      A.A. Hussain, W.H. Chan, J. Marshall; Potential Usefulness of AGE Cross–Link Breakers for Modulating the Progression of AMD . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1211.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: To assess the beneficial effects of advanced glycation end–product (AGE) cross–link breakers on the ultrastructural and functional transport properties of ageing human Bruch’s membrane. Methods: The elasticity of Bruch’s was determined by a newly developed OCT–based imaging technique. Briefly, a Bruch’s–choroid preparation was clamped in an open Ussing chamber such that the cross–sectional outline of Bruch’s could be captured by the OCT technique. The increase in arc–length of the preparation in response to applied hydrostatic pressures in the range 500–3000 Pa allowed the calculation of the elasticity index of the sample. Hydraulic conductivity was estimated by following the drop in hydrostatic pressure as fluid flowed through the membrane whilst held in the Ussing chamber. Diffusional status was quantified with respect to the movement of a 21.2 kDa FITC–dextran in standard Ussing chambers. After quantification of these structural and functional parameters, the samples were incubated with 10mM of the cross–link breaker phenacylthiazolium bromide (PTB) for 12 hours and parameters re–evaluated. Results: Incubation with PTB improved the elasticity of Bruch’s membrane at both macular (7 donors, age range 45–90 years, p< 0.05) and peripheral (10 donors, age range 21–90 years, p< 0.001) locations. Average improvement in elasticity in macular and peripheral regions was 30 and 55% respectively. A single PTB incubation was also very effective in increasing conductivity (p< 0.001; 31–91 years, 14 donors) and diffusional status (p< 0.05; 42–79 years, 8 donors) to levels normally associated with donors 30 years younger. Conclusions: The improvement in ultrastructural and functional parameters of ageing human Bruch’s membrane following treatment with AGE cross–link breakers suggests an important therapeutic pathway in the management of age–related macular degeneration (AMD). The importance of AGEs, their lipid counterparts ALEs and other oxidative linkages in the aetiological mechanisms underlying the pathophysiology of AMD needs re–evaluation.

Keywords: age-related macular degeneration • Bruch's membrane • extracellular matrix 
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