High iron diet causes elevation of retinal iron levels and RPE autofluorescence

Abstract

Purpose: The blood-retinal barrier plays a significant role in shielding the retina from potentially harmful blood components. Since the retina is particularly sensitive to iron levels, it is crucial to understand the impact systemic iron overload has on retinal iron levels.

Methods: Male CD1 strain wild type mice were fed a Harlan Teklad diet with 2% iron carbonyl compared to mice fed the same diet without the carbonyl iron for 3 or 10 months. The retinas were analyzed with immunofluorescence to assess the levels of iron and iron-regulated proteins. mRNA levels of retinal and isolated RPE L-ferritin, transferrin receptor, and oxidative stress markers were measured by qPCR.

Results: H-ferritin and L-ferritin immunoreactivity (which is directly correlated with iron levels) in the neural retina (NR) and retinal pigment epithelium (RPE) was increased in the iron-supplemented diet mice compared to normal diet mice. Additionally, there were increased mid-cytoplasmic punctate autofluorescent spots in the RPE in the high iron diet mice when compared to the normal diet mice. Interestingly, antioxidant genes, superoxide dismutase (SOD1, SOD2) mRNAs were significantly decreased in the high iron diet mice.

Conclusions: These findings indicate that the iron absorbed in the diet can increase the level of iron deposition in the NR and RPE. Surprisingly, the oral iron can cross the blood-retinal-barrier, increasing retinal iron levels. Furthermore, the increased RPE autofluorescence suggests lipofuscin deposition in the RPE, which could be harmful over time. Moreover, decreased SOD suggests a compensatory reaction by the RPE to reduce hydrogen peroxide production in order to reduce the harmful affects of the Fenton reaction, in the high iron diet mice.