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Lily L. Wong, Quentin N. Pye, Lijuan Chen, Xue Cai, Sudipta Seal, James F. McGinnis; Assessing the Therapeutic Effect of Nanoceria in an Autosomal Dominant Retinitis Pigmentosa Model. Invest. Ophthalmol. Vis. Sci. 2012;53(14):282.
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Nanoceria are inorganic and possess catalytic antioxidant activity in biological systems. They scavenge reactive oxygen species (ROS) and act as an oxygen buffer. Because chronic rise in ROS is a hallmark in many forms of retinal degeneration, we hypothesize that reduction of ROS levels in the retina will be beneficial in preserving the health of retinal cells in retinitis pigmentosa irrespective of the gene defect, thus prolonging vision.
We used the P23H-1 rats to assess the efficacy of nanoceria in preservation of rod and cone functions, and retinal cytoarchitecture. The P23H rat is amodel for the condition of autosomal dominant retinitis pigmentosa (adRP). Patients lose their rod cells initially followed by the loss of cone cells later in life. Among the three lines of P23H rats, line 1 exhibits the fastest rate of degeneration. By 8 weeks of age, scotopic a-, and b-wave amplitudes were about 20%, and 60% of wildtype, respectively. Photopic b-wave amplitude was 56% of wildtype. We examined the efficacy of nanoceria over a span of 4 to 7 weeks post injection and evaluated retinal function by electroretinography and retinal cytoarchitecture by optical coherence tomography (OCT) and histology.
When a single dose of nanoceria was injected intravitreally before 3 weeks of age, we observed increased rod function up to five weeks post injection. However, by seven weeks post injection, we did not observe changes in rod function between nanoceria and saline injected animals. We also observed a moderate increase in cone function in nanoceria injected animals five weeks post injection.
We validated that nanoceria were effective in preserving rod function in an adRP rat model. This represents the fourth rodent retinal disease models that show delay in disease progression after a single application of nanoceria. Since the protection lasted for a limited period, we speculate that repeated dosing may be effective in extending the length of retinal function. We hypothesizethat combining another therapeutic regiment concomitantly or in tandem may further prolong the functional life span of diseased rod cells in adRP. This non-gene-targeted therapeutic strategy should aid in the preservation of vision until more effective and affordable gene therapy is developed for PR patients.
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