Abstract
Abstract: :
Purpose: This work assessed the hypothesis that drusen and decreased choroidal blood flow impede the transport of small molecules such as oxygen and hydrogen ions across the retina in age-related macular degeneration (ARMD). Methods: We modified mathematical models for O2 and H+ diffusion in the outer retina to perform simulations of O2 and H+ transport under conditions mimicking ARMD. The modified models recognize that drusen move the neural retina further from the choroid than is normal. This required the conversion of the previously-developed three-layer retinal diffusion models into four-layer diffusion models in which the added layer consisted of drusen. There are no definitive values for the transport properties of the additional layer, so they were varied over a range of possible physiological values. Other parameter values were based on those previously obtained for the cat retina. Drusen size and choroidal blood flow were varied to determine the effect of these variables on oxygen and hydrogen ion concentrations and photoreceptor oxygen consumption. Results: Decreasing choroidal blood flow by a factor of two resulted in a small decrease in the amount of oxygen that reaches the photoreceptors. The factor that had the most detrimental effect on the transport was drusen size. Even a druse that was 25 µm high reduced oxygen transport sufficiently that photoreceptor oxygen consumption would be expected to decrease to 40 to 65% of normal, depending on the transport parameters assumed for the drusen layer. The presence of drusen also acidified the outer retina, but the effects were not as profound as those on O2. Conclusion: The presence of a drusen layer adds a significant oxygen transport resistance, thereby reducing the supply of oxygen to the photoreceptors. This could contribute to the pathogenesis of ARMD.
Keywords: 308 age-related macular degeneration • 555 retina: distal(photoreceptors, horizontal cells, bipolar cells) • 561 retinal degenerations: cell biology