Measurement of Mitochondrial ROS Production in Mouse Models of Photoreceptor Degeneration

Retinitis pigmentosa (RP) is a disease characterised by photoreceptor cell death. It can be initiated by mutations in a number of different genes, primarily affecting rods, which will die first, resulting in loss of night vision. The secondary death of cones then leads to loss of visual acuity and blindness. We set out to investigate whether increased mitochondrial reactive oxygen species (ROS) formation, plays a role in this sequential photoreceptor degeneration. To do this we measured mitochondrial HO production within mouse eyes using the mass spectrometric probe MitoB. We found higher levels of mitochondrial ROS that preceded photoreceptor loss in four mouse models of RP: . In contrast, there was no increase in mitochondrial ROS in loss of function models of vision loss (), or where vision loss was not due to photoreceptor death (). Upregulation of transcriptional activity with dimethylfumarate (DMF) lowered mitochondrial ROS in mice. These findings have important implications for the mechanism and treatment of RP.