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R. Lai, G. Wu, D. Sao, J. Edelman; Protection of Cone Photoreceptors in the Rat Model of Retinitis Pigmentosa S334ter by Antioxidants. Invest. Ophthalmol. Vis. Sci. 2009;50(13):698.
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Retinitis pigmentosa (RP) is a group of diseases in which many different mutations cause rod photoreceptor cell death. The disease is characterized by a subsequent loss of cone photoreceptors. Recent studies in the rd mouse models suggested that this cone cell death might be oxidative stress related. In this study, we tested the effectiveness of antioxidants in preserving cone photoreceptors in the transgenic S334ter RP rat model.
40d old S344ter rats were given daily systemic injections of an antioxidant mixture including -tocopherol (200 mg/kg), ascorbic acid (250 mg/kg), -lipoic acid (100 mg/kg) and MnTBAP (10 mg/kg). At 70 and 90 day time points, retinas were isolated from antioxidant treated animals and age-matched S334ter control rats and stained with flourescent tagged PNA. Confocal microscopy was utilized to detect and image the cone photoreceptors in retina, flatmounted with photoreceptor side up. The number of cone photoreceptors was quantified with the ImagePro software at various regions of the retina. Additionally, retinas isolated from the contralateral eyes were processed, sectioned, H&E stained and evaluated for total photoreceptor cell loss.
Between day 40 and day 70, there was a significant loss of photoreceptors in these S334ter rats. The number of photoreceptor nuclei was reduced to about 4 to 5 rows. Significant loss of cone photoreceptors was observed in the superior retina, 1000u to 2000u from the optic nerve head. The degeneration of the cone photoreceptors was characterized by isolated areas lacking PNA staining. On day 90, photoreceptor layer was reduced to 1 to 2 rows. Loss of cone photoreceptors was observed throughout the superior retina and diffusely in the nasal and inferior regions. In animals treated with daily antioxidant injections, the number of cone photoreceptors was significantly greater than in control animals at each time point. By day 90, antioxidant treated animals had almost 15% more cone photoreceptors in the superior retina than in the control S334ter rats.
Antioxidants were found to significantly reduce the cone cell photoreceptor death in the transgenic S334ter rats. This strongly suggests that oxidative stress plays a major role in cone photoreceptor death in retinitis pigmentosa and that antioxidant may be a potential therapy for retinitis pigmentosa.
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