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L. L. Wong, D. M. Hancin, S. Seal, J. Chen, J. F. McGinnis; Sensitivity of Cones to Intracellular Peroxide Damage and Protection by Inorganic Cerium Oxide Nanoparticles. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4786.
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Light-induced retinal degeneration is characterized by thinning of the outer-nuclear layer and the drastic reduction of a-, and b-wave amplitudes in scotopic electroretinograms. Both of these conditions measure the number and function of rod photoreceptor cells. Unlike rods, cones do not saturate with light and little is known regarding their fate in light-damage models. To address this, we studied the effects of bright light on the health of cones in albino rats and asked whether cerium oxide (CeO2) nanoparticles (Nanoceria) could protect cones.
Sprague-Dawley albino rats (8 to 12 weeks old) kept under cyclic light conditions (12 h on/12 h off, 5-20 lux ) were injected intravitreally with 2 µL of either saline or CeO2 nanoparticles in saline. Three days later they were exposed to 2700 lux light for 6 h, returned to cyclic light conditions for 7 days before termination. Five µm thick paraffin retinal sections were used for immunohistochemistry. Cone outer segments (COS) were identified using an L/M opsin antibody (Chemicon; 1:2000) and visualized with HRP-DAB.
Bright light exposure for 6 h caused severe cone damage especially in the superior portion of the central retina. The COS length was used as a criterion for healthy cones. We measured the length of all the COS in a region of the central retina between 1.5-2.0 mm from the optic nerve head in the superior region. Those that were longer than the half maximum length were counted as healthy cones. In retinas of light exposed, saline injected or uninjected animals, we did not observe any healthy cones. In retinas of Nanoceria injected and light exposed animals, we observed a dose-dependent protection of cones.
Our data demonstrate severe damage to cones by bright light, their protection by Nanoceria and suggest that the Nanoceria may also be therapeutic for cones in other retinal diseases such as macular degeneration, retinitis pigmentosa, diabetic retinopathy, retinal detachment, etc. Our data also strongly support the use of the light damage model as an assay for analysis of the neuroprotective effects of potential therapeutic agents.
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