Manipulations of ACHE gene expression suggest non-catalytic involvement of acetylcholinesterase in the functioning of mammalian photoreceptors but not in retinal degeneration

Ron S. Broide, Mirta Grifman, Anat Loewenstein, Dan Grisaru, Rina Timberg, Jonathan Stone, Moshe Shani, James W. Patrick, Hermona Soreq*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

To explore role(s) of acetylcholinesterase (AChE) in functioning and diseased photoreceptors, we studied normal (rd/+) and degenerating (rd/rd) murine retinas. All retinal neurons, expressed AChEmRNA throughout fetal development. AChE and c-Fos mRNAs peaked at post-natal days 10-12, when apoptosis of rd/rd photoreceptors begins. Moreover, c-Fos and AChEmRNA were co-overexpressed in rd/rd mice producing transgenic human (h), and host (m) AChE, but not in rd/+ mice. However, mAChE overexpression also occurred in transgenics expressing human serum albumin. Drastic variations in AChE catalytic activity were ineffective during development. Neither transgenic excess nor diisopropylfluorophosphonate (DFP) inhibition (80%) affected the rd phenotype; nor did DFP exposure induce photoreceptor degeneration or affect other key cholinergic proteins in rd/+ mice, unlike reports of adult mice and despite massive induction under DFP of c-Fos overproduction. In human embryos (20 weeks), most retinal neurons express AChEmRNA. Surprisingly, only the continually remodeling photoreceptors express AChEmRNA in aged humans (> 70 years). Therefore, the extreme retinal sensitivity to AChE modulation may reflect non-catalytic function(s) of AChE in adult photoreceptors. These findings exclude AChE as causing the rd phenotype, suggest that its primary function(s) in mammalian retinal development are non-catalytic ones and indicate special role(s) for the AChE protein in adult photoreceptors.

Original languageEnglish
Pages (from-to)137-148
Number of pages12
JournalMolecular Brain Research
Volume71
Issue number2
DOIs
StatePublished - 25 Aug 1999

Keywords

  • Cholinesterase inhibitor
  • Gene, fos
  • In situ hybridization
  • Mice, transgenic
  • Photoreceptor, vertebrate

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