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L.E. Johnson, L. Wilke, T. Talukdar, L. Taylor, T. van Veen, P. Ekström; Oxidative Damage in the rd1 Mouse Retina . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1025.
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Retinitis Pigmentosa (RP) is a group of inherited diseases which result in the degeneration of rod photoreceptors. The loss of these cells in turn leads to the death of cone photoreceptors and thereby blindness. A model for studying this condition is the rd1 mouse which carries a mutation causing the rods to die via apoptosis shortly after birth. As with human RP, the rd1 cones cannot survive without the rods and therefore subsequently die. It has been shown in other RP animal models that this secondary cone death may be linked to oxidative stress. In the present work, we studied whether rd1 rods also showed signs of oxidative stress and if markers for this correlated with apoptotic labelling.
Retinas were collected from both normal and rd1 mutant C3H mice at various time points between postnatal day 9 (P9) and P15, paraformaldehyde fixed and cryosectioned at 8–12 µm. Sections were then stained using TUNEL and antibodies against 8–hydroxydeoxyguanosine, a marker for oxidatively damaged DNA. In addition, other indicators of oxidative stress were used in colabelling experiments with these two markers.
Sporadic staining for 8–hydroxydeoxyguanosine was seen in the inner nuclear layer of both normal and rd1 retinas of the youngest samples and is likely related to developmental apoptosis. In contrast, 8–hydroxydeoxyguanosine positive cells were only seen in the outer nuclear layer of rd1 retinas. Cells with oxidatively damaged DNA were present in the rd1 outer nuclear layer at all ages studied in a central–peripheral gradient, correlating with the pattern of photoreceptor degeneration in this model. Furthermore, staining for 8–hydroxydeoxyguanosine and other markers of oxidative stress correlated with TUNEL positive cells.
Degenerating rod photoreceptors in the rd1 mouse showed clear signs of oxidative damage. It may be that the oxidative damage pushed the rods into undergoing apoptosis, although the possibility that the damage is a result of apoptotic processes cannot be excluded. If oxidative damage is a promoter of hereditary photoreceptor death, then antioxidants should be investigated as a viable therapy for RP.
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