Oral proton pump inhibitors disrupt horizontal cell-cone feedback and enhance visual hallucinations in macular degeneration patients

Anne M. Hanneken, Norbert Babai, Wallace B Thoreson

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Purpose. 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.

Original languageEnglish (US)
Pages (from-to)1485-1489
Number of pages5
JournalInvestigative Ophthalmology and Visual Science
Volume54
Issue number2
DOIs
StatePublished - Feb 1 2013

Fingerprint

Proton Pump Inhibitors
Hallucinations
Macular Degeneration
Retinal Neurons
Amphibians
Patch-Clamp Techniques
Wet Macular Degeneration
Retina
Ophthalmodynamometry
Color Perception
Benzimidazoles
Ganglia
Membrane Potentials
Cognition
Cell Membrane
Calcium
Light
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Oral proton pump inhibitors disrupt horizontal cell-cone feedback and enhance visual hallucinations in macular degeneration patients. / Hanneken, Anne M.; Babai, Norbert; Thoreson, Wallace B.

In: Investigative Ophthalmology and Visual Science, Vol. 54, No. 2, 01.02.2013, p. 1485-1489.

Research output: Contribution to journalArticle

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