title: Retinal and cochlear toxicity of drugs:  new insights into mechanisms and detection.
abstract: OBJECTIVE
  Various medications can modify the physiology of retinal and cochlear neurons and lead to major, sometime permanent, sensory loss. A better knowledge of pathogenic mechanisms and the establishment of relevant monitoring protocols are necessary to prevent permanent sensory impairment. In this article, we review main systemic medications associated with direct neuronal toxicity on the retina and cochlea, their putative pathogenic mechanisms, when identified, as well as current recommendations, when available, for monitoring protocols.
  
  
  RESULTS
  Pathogenic mechanisms and cellular target of retinotoxic drugs are often not well characterized but a better knowledge of the course of visual defect has recently helped in defining more relevant monitoring protocols especially for antimalarials and vigabatrin. Mechanisms of ototoxicity have recently been better defined, from inner ear entry with the use of fluorescent tracers to evidence for the role of oxidative stress and program cell death pathways.
  
  
  CONCLUSIONS
  Experimental and clinical studies have elucidated some of the pathogenic mechanisms, courses and risk factors of retinal toxicity and ototoxicity, which have led to establishment of relevant monitoring protocols. Further studies are, however, warranted to better understand cellular pathways leading to degeneration. These would help to build more efficient preventive intervention and may also contribute to understanding of other degenerative processes such as genetic disorders.
authors.affiliation: INSERM, U968, Paris, France. isabelle.audo@inserm.fr
authors.forename: Isabelle
authors.initials: I
authors.lastname: Audo
authors.forename: Mark E
authors.initials: ME
authors.lastname: Warchol
mesh_terms: D016923:Cell Death / Q000187:drug effects; D003051:Cochlea / Q000187:drug effects* / Q000473:pathology*; D064420:Drug-Related Side Effects and Adverse Reactions; D006311:Hearing Disorders / Q000139:chemically induced* / Q000473:pathology; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012160:Retina / Q000187:drug effects* / Q000473:pathology*; D014786:Vision Disorders / Q000139:chemically induced* / Q000473:pathology
chemical_list: D017382:Reactive Oxygen Species