Reactive oxygen species as mediators of photoreceptor apoptosis in vitro

Retinitis pigmentosa is a heterogeneous group of retinal degenerations char acterized by a progressive loss of photoreceptors through the process of ap optosis. The apoptotic cell death of photoreceptors appears to represent a final common pathway in the pathology of retinitis pigmentosa. Previous stu dies have reported the ability of antioxidants to ameliorate light-induced retinal degeneration, suggesting a role for oxidative stress in photorecept or cell death. This study demonstrates an early and sustained increase in i ntracellular reactive oxygen species accompanied by a rapid depletion of in tracellular glutathione in an in vitro model of photoreceptor apoptosis. Th ese early changes in the cellular redox state precede disruption of mitocho ndrial transmembrane potential, nuclear condensation, DNA nicking, and cell shrinkage, all of which are well-characterized events of apoptotic cell de ath. The ability of zinc chloride and pyrrolidine dithiocarbamate, two esta blished antioxidants, to inhibit photoreceptor apoptosis through the scaven ging of intracellular reactive oxygen species establishes a role for reacti ve oxygen species as possible mediators of in vitro photoreceptor apoptosis . This study provides a molecular basis for the inhibition of photoreceptor apoptosis by antioxidants. (C) 1999 Academic Press.