title: Digoxin-induced reversible dysfunction of the cone photoreceptors in monkeys.
abstract: OBJECTIVE
  To investigate functional alteration of the retina induced by digoxin in monkeys.
  
  
  METHODS
  Digoxin was intravenously administered to cynomolgus monkeys and standard full-field electroretinograms (ERGs) were serially recorded. In other digoxin-treated monkeys, the rod and cone a-waves to high-intensity flashes were obtained and analyzed by the a-wave fitting model (a-wave analysis). The following responses were also recorded: dark- and light-adapted responses to flashes of different intensities (dark- and light-adapted luminance responses), photopic ERG elicited by long-duration stimulus (ON-OFF response), and the photopic negative response (PhNR).
  
  
  RESULTS
  Delayed b-wave was observed in all responses of the standard full-field ERGs; amplitude of the b-wave was increased in the rod response, but was decreased in the single-flash cone response and the 30-Hz flicker. These changes recovered gradually after elimination of digoxin from the blood. Digoxin enhanced and delayed the b-wave in the dark-adapted luminance-response analysis regardless of stimulus intensity. In the light-adapted luminance-response analysis, digoxin attenuated the a- and b-waves only at high and middle stimulus intensity, respectively. The a-wave analysis revealed selective decrease in the maximum response parameter (Rmax) in the cone a-wave. Both the b- and d-waves of the ON-OFF response were delayed.
  
  
  CONCLUSIONS
  The selectively reduced Rmax in the cone a-wave indicated dysfunction of the cone photoreceptors in digoxin-treated monkeys. Meanwhile, the enhanced and delayed rod response suggested alteration of retinal components other than the cone photoreceptors. These results may contribute to the understanding of digoxin-induced visual disturbances in humans. It is suggested that the cone function is markedly, but not exclusively, affected in the retina of such patients.
authors.affiliation: Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Kita-Kasai, Edogawa-ku, Tokyo, Japan.
authors.forename: Junzo
authors.initials: J
authors.lastname: Kinoshita
authors.forename: Noriaki
authors.initials: N
authors.lastname: Iwata
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Kimotsuki
authors.forename: Mitsuya
authors.initials: M
authors.lastname: Yasuda
mesh_terms: D000818:Animals; D003623:Dark Adaptation; D004077:Digoxin / Q000493:pharmacokinetics / Q000633:toxicity*; D004596:Electroretinography / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000633:toxicity*; D007262:Infusions, Intravenous; D008252:Macaca fascicularis; D009887:Ophthalmoscopy; D010775:Photic Stimulation; D017949:Retinal Cone Photoreceptor Cells / Q000187:drug effects* / Q000201:enzymology; D012164:Retinal Diseases / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D014786:Vision Disorders / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology*
chemical_list: D004791:Enzyme Inhibitors; D004077:Digoxin; D000254:Sodium-Potassium-Exchanging ATPase
keywords: cones; digoxin; electroretinogram; monkey; visual disturbance