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MINIREVIEW

Oxidative Stress Plays an Important Role in the Pathogenesis of Drug-Induced Retinopathy

Pfizer Inc., New London, Connecticut 06320

To whom requests for reprints should be addressed at ¹ Clinical Safety and Risk Management, Pfizer Inc., Pfizer Global Research and Development, 50 Pequot Avenue, New London, CT 06320. E-mail: steven_m_toler{at}groton.pfizer.com

Several pharmaceutical agents have been associated with rare but serious retinopathies, some resulting in blindness. Little is known of the mechanism(s) that produce these injuries. Mechanisms proposed thus far have not been embraced by the medical and scientific communities. However, preclinical and clinical data indicate that oxidative stress may contribute substantially to iatrogenic retinal disease. Retinal oxidative stress may be precipitated by the interaction of putative retinal toxins with the ocular redox system. The retina, replete with cytochromes P450 and myeloperoxidase, may serve to activate xenobiotics to oxidants, resulting in ocular injury. These activated agents may directly form retinal adducts or may diminish ocular reduced glutathione concentrations. Data are reviewed that suggest that indomethacin, tamoxifen, thioridazine, and chloroquine all produce retinopathies via a common mechanism—they produce ocular oxidative stress.

Key Words: oxidative • stress • drug • retinopathy • myeloperoxidase

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