Figure 7.

Predicted model of retinal iron transport before our current studies and revised model of retinal iron transport after our current studies. Before our current studies, we hypothesized that a large portion of iron that enters the neural retina comes from the choroidal circulation via RPE cells (green arrows). We also hypothesized that some iron in the neural retina is from the retinal vasculature (gold arrows). In addition, we did not know which retinal cells express the ferroxidases Cp, Heph, APP, and Zp. From our current studies, we determined that the RPE cells express Cp, Heph, and APP, but not Zp, and that Muller cells express transferrin receptor (TfR), ferroportin, Cp, Heph, APP, and Zp. We found that Cp and Heph are important for iron export from the neural retina but not for iron import into the neural retina. Our current studies support a model in which the retina is divided into two compartments, the Muller and RPE cell compartments, with Muller and RPE cells regulating iron levels in their respective compartments. The external limiting membrane (ELM) separates the two compartments. Our studies suggest that the choroidal vasculature mainly supplies iron to the RPE compartment (green arrows), whereas the retinal vasculature supplies iron to the Muller compartment via the Muller cells (gold arrows).