Abstract
Purpose::
Antioxidants reduce cone cell death in rd1 mice, indicating that cones die from oxidative damage in that model of retinitis pigmentosa (RP). In this study, we sought to determine if this observation could be generalized to other models of RP, in particular rd10 mice in which retinal degeneration occurs more slowly than in rd1 mice.
Methods::
Between P18 and P35, rd10 mice received daily i.p. injections of vehicle or a mixture of antioxidants containing alpha-tocopherol (200mg/kg), ascorbic acid (250mg/kg), MnTBAP (10mg/kg), and alpha-lipoic acid (100mg/kg). Scotopic and photopic ERGs were performed at P25 and P35 for evaluation of rod and cone function. Outer nuclear layer (ONL) thickness was measured at P25 and P35, and cone density was measured by confocal microscopy in peanut agglutinin (PNA)-stained retinal flat mounts at P35. The level of rhodopsin mRNA was measured at P25 by quantitative real time RT-PCR.
Results::
Treatment of rd10 mice with antioxidants between P18 and P35 resulted in a greater than 2-fold, statistically significant increase in cone density. There was preservation of cone function as shown by a significant increase in photopic ERG b-wave amplitudes. Antioxidant treated mice also showed a delay in rod cell death with a greater mean ONL thickness and a 69% increase in the level of rhodopsin mRNA at P25, accompanied by a significant increase in scotopic a- and b-wave amplitudes. The preservation of rod structure and function was temporary, because statistically significant differences were lost by P35.
Conclusions::
These data demonstrate that cones die from oxidative damage in a second model of RP, and that in rd10 mice in which the rod degeneration is much slower than in rd1 mice, oxidative damage also contributes to and accelerates rod cell death.
Keywords: antioxidants • oxidation/oxidative or free radical damage • retinal degenerations: hereditary