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B.S. Rogers, R.C. A. Symons, Y.Y. Gong, J. Shen, W.H. Xiao, S. Kachi, P.A. Campochiaro; Iron–Mediated Retinal Degeneration: Evidence for Cone Selectivity . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2047.
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© ARVO (1962-2015); The Authors (2016-present)
To examine the effects of intravitreous injection of iron on mouse retina.
Adult C57BL/6 mice were given an intravitreous injection of saline or 0.10, 0.25, or 0.50mM FeSO4. Scotopic ERGs were performed 1, 7, and 14 days after injection. Photopic ERGs were performed at day 14. Mice were sacrificed at 1, 2, 3, and 14 days after injections. Histological sections were stained for TUNEL and hydroxynonenal (HNE), and superoxide was detected via hydroethidine staining. Outer nuclear layer (ONL) thickness was quantified at day 14. Real time PCR to determine cone–opsin and rhodopsin expression was performed at 12 days.
Oxidative stress histological markers: Three days after FeSO4 injections, there was increased staining for HNE in the outer retina. In mice administered hydroethidine, there was prominent fluorescence in the outer retina, indicating increased levels of reactive oxygen species. TUNEL: Numerous positive nuclei were seen in the outermost portion of the ONL at 1 and 2 days after injection of 0.25mM FeSO4. Positive nuclei were present throughout the ONL at 3 days. ONL thickness: 0.25mM FeSO4 caused a 40% decrease in ONL thickness (p<0.0001) at day 14. ERG: FeSO4 caused significant, dose–dependent decreases in scotopic ERG a– and b–wave amplitudes at 1, 7, and 14 days and in photopic ERG amplitudes at day 14. Reductions in photopic ERG amplitudes were markedly greater than those in scotopic ERG amplitudes. Real time PCR: Twelve days after injection of 0.25mM FeSO4, there was a 6.65–fold reduction in expression of M–cone opsin (p=0.0004 ) and a 7.07–fold reduction in expression of S–cone opsin (p=0.01). There was not a significant reduction in expression of rhodopsin.
Intravitreous injection of iron causes oxidative stress in the retina, resulting in apoptosis of photoreceptors, reduced ONL thickness, and reduced scotopic and photopic ERGs. Cones are differentially sensitive to the damaging effects of iron, indicating a possible difference in the oxidative defense system of rods and cones.
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