Macromolecular diffusion characteristics of ageing human Bruch's membrane: implications for age-related macular degeneration (AMD).

Macromolecular species such as retinal binding protein, transferrin, ceruloplasmin, etc., released by the fenestrated choroidal capillaries must diffuse across Bruch's membrane for interaction with the basal membranes of the retinal pigment epithelium (RPE) for delivery of essential metabolites to the neural retina. The patency of this pathway through ageing Bruch's was examined by quantifying the diffusional flux of a 21.2 kDa fluorescein-isothiocyanate labelled dextran. Dextran flux measurements across Bruch's membrane from the macular region of the human fundus showed a highly significant decrease (p < 0.001) with ageing of donor such that diffusional transport in the ninth decade was about 6.5% of that in the first decade of life. Peripheral regions also showed a highly significant decline (p < 0.001) but ageing changes were considerably slowed in comparison to the macula with diffusional rates in the ninth decade being about 44% of that in the first decade. Peripheral samples from AMD donors displayed diffusional rates that were lower than the control population. The age-related decline in macromolecular diffusion across Bruch's membrane suggests that in the elderly, the patency of the conducting pathways may be compromised and in the more advanced ageing of Bruch's associated with AMD, the metabolic trafficking of carrier proteins may be severely impaired.