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Xue Cai, Steven A. Sezate, Sudipta Seal, James F. McGinnis; Long Term Protection of Photoreceptors By Nanoceria In Tubby Mice. Invest. Ophthalmol. Vis. Sci. 2011;52(14):423.
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© ARVO (1962-2015); The Authors (2016-present)
The tubby mouse arose from a mutation in Tub gene and exhibits retinal and cochlear degeneration. Previously we demonstrated that light exposure enhances retinal degeneration in tubby mice and that reactive oxygen species (ROS) are involved in this process. Also, injection of suforaphane or expression of a thioredoxin transgene can slow retinal degeneration due to the Tub defect. Cerium oxide nanoparticles (nanoceria) have been shown to catalytically scavenge ROS and prolong vision in a rat light-damage model. Here we test the hypothesis that nanoceria can prevent inherited retinal degeneration in tubby mice.
Tubby pups were intravitreally injected with 1µl of 1mM nanoceria at P7. Untreated mutant, wild type (wt) mice and saline injection served as controls. The effect of nanoceria on retinal structure and function was assessed by ERG and quantitative histology at P28, P49 and P120; Oxidative stress associated gene expression was analyzed using mouse oxidative stress and antioxidant defense PCR array (SABiosciences) at P28. The expression of photoreceptor-specific genes and caspase-3 was analyzed by qRT-PCR and western blots.
At P28, numerous genes associated with protection from oxidative stress were upregulated whereas genes involved in oxidase production, DNA damage and cell death were downregulated by nanoceria. Expression of rhodopsin, arrestin and s-opsin was increased while expression of caspase-3 was reduced in nanoceria treated eyes compared to uninjected and saline injected samples. Outer nuclear layer thickness in saline treated eyes was 51% of wt level and nanoceria treated eyes reached 75% of wt level. The amplitude of scotopic a-, b- wave and photopic b-wave elevated 82%, 63% and 100%, respectively, by nanoceria treatment compared to saline injected animals. These effects are sustained through P49. Assessments for P120 are ongoing.
Nanoceria act as antioxidants to regulate oxidative stress associated gene expression. They up-regulate photoreceptor-specific gene expression, prevent apoptosis of photoreceptor cells and thereby promote photoreceptor survival, maintain retinal structure and function and slow inherited retinal degeneration.
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