Abstract
Purpose: :
To evaluate the contribution of disease processes associated with AMD to the age-related decline in the hydraulic conductivity of Bruch’s membrane.
Methods: :
Bruch’s-choroid samples were isolated as 8mm discs from the peripheral regions of donor human eyes and mounted in purpose-built Ussing-type chambers. A hydrostatic pressure head of 14-16mmHg (IOP) was applied to the Bruch’s side of the preparation and the resulting fall in pressure as fluid moved through the tissue complex was used to calculate the hydraulic conductivity of the preparation. The data from the control population (90 eyes, age range 1-91 years) was used to obtain an age profile for changes in hydraulic conductivity. This profile was compared with data from 12 donors with AMD, age-range 64-95 years.
Results: :
In the peripheral fundus of normal donor eyes, hydraulic conductivity of Bruch’s membrane declined exponentially with age and was described by the relationship HC = A x e (-k*age) where A was equal to 101.5 x10-10 m/s/Pa and k, the decay constant was 0.0299, r=0.82 (n=90). The half-life of the decay process was calculated to be 23 years, i.e., conductivity of Bruch’s membrane was halved for every 23 years of life. The minimum hydraulic conductivity (failure threshold) of Bruch’s required to process fluid output from human RPE was calculated to be 0.57 x10-10 m/s/Pa. Thus, in the normal population, the capacity for transport across Bruch’s remained well above the minimum requirement over a human life-span. In fact, the trend line of the decay process would meet the failure threshold at an age of 173 years, well outside human life expectancy. The hydraulic conductivities of Bruch’s from AMD donors all fell below the normal tend line with one donor (aged 86 years) crossing the failure threshold.
Conclusions: :
In AMD donor eyes, the age-related decline in hydraulic conductivity of Bruch’s membrane is accelerated with capacity to reach failure threshold within the life span of an individual. Since these ageing changes are much more advanced at macular locations, these results provide an explanation for the higher incidence of RPE detachments in AMD patients. Moreover, the early failure in fluid transport capability is likely to provide an early insult to the RPE-photoreceptor complex that may be the basis of transition to the pathological phase of the disease process.
Keywords: age-related macular degeneration • Bruch's membrane • aging