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Developmental iron uptake and axonal transport in the retina of the rat
1Section of Neurobiology, Biomedicine, Aalborg University, Denmark. tmoos@hst.aau.dk
Insights
Iron uptake in the rat retina is age-dependent, with transferrin facilitating iron transport to retinal ganglion cells for axonal transport. This study details iron distribution and uptake in developing and adult rat eyes.
Area of Science:
- Ophthalmology
- Neuroscience
- Developmental Biology
Background:
- Iron is essential for retinal function, but its precise distribution and transport mechanisms, particularly during development, remain incompletely understood.
- Understanding iron homeostasis in the retina is crucial for addressing neurodegenerative conditions affecting vision.
Purpose of the Study:
- To investigate the age-dependent distribution and uptake of iron in the rat eye, with a focus on the retina.
- To elucidate the role of transferrin in iron transport within the retina and its axonal transport by retinal ganglion cells.
Main Methods:
- Utilized Perls' stain to visualize iron distribution in rat retinas at different postnatal ages (P1, P16, P30, P70).
- Administered radiolabeled iron-bound transferrin intravenously and via intravitreal injection in rats of varying ages.
- Quantified iron uptake using volume of distribution (V(D)) and employed emulsion autoradiography and immunoprecipitation to track iron and its binding proteins.
Main Results:
- Iron concentration in the eye varied with age, showing a peak at P1 and P70, with lower levels at P30.
- Retinal iron labeling intensified with age, shifting from macrophages in the choroid to widespread retinal cells.
- Intravenous and intravitreal administration of (59)Fe-transferrin showed significantly higher iron uptake than transferrin or albumin, with iron transported anterogradely in retinal ganglion cell axons.
Conclusions:
- The study demonstrates a continuous, age-dependent iron uptake by the rat retina.
- Transferrin plays a key role in delivering iron to retinal cells, including photoreceptors and ganglion cells.
- Retinal ganglion cells transport iron anterogradely via axonal transport, with iron detaching from transferrin within the axons.
Abstract:
We examined differently aged postnatal (P) rats for the distribution and uptake of iron in the eye with the main emphasis on iron uptake in the retina. The concentration of iron in the eye was 48 μg/g in rats aged one postnatal day (P1). Then concentration fell to approximately 12 μg/g at P30 and rose to 35 μg/g at P70. Perls' stain which labels both ferrous and ferric iron was found to exhibit a weak labeling in the retina at P1 contrasted by a robust labeling of macrophages found in the choroid of the retina. In older aged rats, the labeling of cells of the retina was much more intense and confined to cells widespread in the layers of the retina. In both P16 and adult rats injected intravenously with [(59)Fe-(125)I]transferrin, the uptake of (59)Fe, estimated as the volume of distribution, was significantly higher than that of [(125)I]transferrin, and uptake of both compounds was higher than that of simultaneously injected [(131)I]albumin. In the P16 rat, the uptake of (59)Fe expressed as the volume of distribution, V(D), rose linearly reaching approximately 2500 nl at 60 min. In the adult rat, the uptake of (59)Fe was of the same magnitude. Comparing P1 and P16 rats, the uptake of (59)Fe, [(125)I]transferrin and [(131)I]albumin was higher at P1 in both eyeball and retina. Emulsion autoradiography of retinas from P16 and adult rats injected with [(55)Fe]transferrin into the vitreous body showed uptake mainly in photoreceptor cells and retinal ganglion cells. Adult rats injected into the vitreous body with [(59)Fe]transferrin showed anterograde axonal transport from the retina into the optic nerve, optic tract, and superior colliculus. Immunoprecipitates of homogenates of the optic nerve revealed that (59)Fe was precipitable with an antibody raised against ferritin, indicative of detachment of iron from transferrin within the axons of the retinal ganglion cells. The data demonstrate an age-dependent but continuous iron uptake by the retina, and are indicative of anterograde axonal transport of transferrin by retinal ganglion cells.
