Beneficial Effect of Antioxidants in Retinopathies: A New Hypothesis

The retina is the most oxygen consuming tissue of the body. Rod and cone photoreceptors efficiently carryout visual cascades, which are energetically costly processes. Data has recently been published thatsuggests that the metabolic support to phototransduction in the rod outer segment (OS) may originatedirectly in the OS, which is able to conduct aerobic metabolism. This oxygen-handling activity of the rod OS,which was never suspected before, appears to be a primary cause of the generation of reactive oxygenspecies directly inside the OS. Oxidative stress has been hypothesised to contribute to most of theneurodegenerative retinal pathologies, such as diabetic retinopathy, age-related macular degeneration,retinitis pigmentosa and photoreceptor cell death after retinal detachment. Many natural antioxidantcompounds are routinely used in experimental or human therapies for preventing or delayingphotoreceptor degeneration in those pathologies. Here it is proposed that the ultimate reason for thebeneficial actions of antioxidants in preventing or retarding the effect on the retinal degenerativepathologies can be found in their action on reactive oxygen species generated by the ectopic mitochondrialelectron transport chain (ETC) coupled to FoF1-ATP synthase in rod OS disks. In fact, if not adequatelycoupled, the ETC generates reactive oxygen species that, in turn, can act on the polyunsaturated fatty acidswhich the rod OS is rich in. If correct, the mechanism put forward here would provide a potential for themolecular basis of therapies with antioxidants for retinal degenerative diseases.