Mechanism of the development of thioridazine retinopathy

Comparative electron microscopic, electrophysiological and biochemical studies of thioridazine influence on lipid peroxidation in vivo (rats, rabbits) and in vitro (model systems) were performed. It was shown that thioridazine retinopathy was not followed by an increase in lipid peroxidation and antioxidant (dibunol) failed to protect the retina against the destructive action of thioridazine. Moreover, thioridazine inhibited lipid peroxidation in model system.     

Inhibition by melanin of lipid photo-oxidation

Removal of melanosomes from retinal pigment epithelium cells is accompanied by a sharp rise in the rate of VIS light-induced lipid peroxidation. The synthetic DOPA-melanin effectively suppresses the UV light-induced lipid peroxidation of cardiolipin not only through a passive decrease of irradiation (optical screening), but also by active chemical inhibition of the reaction. It is assumed that the observed active inhibition is due to the interaction between DOPA-melanin and the free radical products generated in cardiolipin upon UV illumination. It is concluded that the high photoresistance of melanin-containing cells of retinal pigment epithelium is due to the ability of melanosomes to exert strong inhibition of photo-induced lipid peroxidation.