title: Oral proton pump inhibitors disrupt horizontal cell-cone feedback and enhance visual hallucinations in macular degeneration patients.
abstract: OBJECTIVE
  Visual hallucinations (VHs) occur in macular degeneration patients with poor vision but normal cognitive function. The underlying mechanisms are poorly understood. We report the identification of pharmaceutical agents that enhance VH and use these agents to examine the contribution of retinal neurons to this syndrome.
  
  
  METHODS
  We detail clinical observations on VH in five macular degeneration patients treated with proton pump inhibitors having the core structure, 2-pyridyl-methylsulfinyl-benzimidazole. We tested possible retinal mechanisms using paired whole cell recordings to examine effects of these compounds on feedback interactions between horizontal cells and cones in amphibian retina.
  
  
  RESULTS
  Five patients with advanced wet macular degeneration described patterned VHs that were induced or enhanced by oral proton pump inhibitors. The abnormal images increased with light, disappeared in the dark, and originated in the retina, based on ophthalmodynamometry. Simultaneous paired whole cell recordings from amphibian cones and horizontal cells showed that 2-pyridyl-methylsulfinyl-benzimidazoles blocked the negative shift in voltage dependence and increase in amplitude of the calcium current (ICa) in cones that is induced by changes in horizontal cell membrane potential. These effects disrupt the negative feedback from horizontal cells to cones that is important for the formation of center-surround receptive fields in bipolar and ganglion cells, and thus for normal spatial and chromatic perception.
  
  
  CONCLUSIONS
  Our study suggests that changes in the output of retinal neurons caused by disturbances in outer retinal feedback mechanisms can enhance patterned visual hallucinations.
authors: Department of Molecular & Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, SP-201, La Jolla, CA 92037, USA. ahanneke@scripps.edu
authors: Anne M
authors: AM
authors: Hanneken
authors: Norbert
authors: N
authors: Babai
authors: Wallace B
authors: WB
authors: Thoreson
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology*; D000369:Aged, 80 and over; D000557:Ambystoma; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004594:Electrophysiology; D005246:Feedback / Q000187:drug effects*; D005260:Female; D005451:Fluorescein Angiography; D006212:Hallucinations / Q000503:physiopathology*; D006801:Humans; D064747:Lansoprazole; D008297:Male; D008564:Membrane Potentials; D009853:Omeprazole / Q000494:pharmacology; D009884:Ophthalmodynamometry; D018408:Patch-Clamp Techniques; D054328:Proton Pump Inhibitors / Q000494:pharmacology*; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology*; D051248:Retinal Horizontal Cells / Q000502:physiology*; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology; D057135:Wet Macular Degeneration / Q000175:diagnosis / Q000503:physiopathology*
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D009853:Omeprazole; D002118:Calcium