A novel isoform of acetylcholinesterase exacerbates photoreceptors death after photic stress.
OBJECTIVE
To study the involvement of stress-induced acetylcholinesterase (AChE) expression in light-induced retinal damage in albino rats.


METHODS
Adult albino rats were exposed for 24 hours to bright, damaging light. AChE expression was monitored by in situ hybridization, by histochemistry for AChE activity, and by immunocytochemistry. An orphan antisense agent (Monarsen; Ester Neurosciences, Ltd., Herzlia Pituach, Israel) was administered intraperitoneally to minimize light-induced AChE expression. The electroretinogram (ERG) was recorded to assess retinal function.


RESULTS
Twenty-four-hour exposure to bright light caused severe reduction in the ERG responses and augmented expression of mRNA for the "read-through" variant of AChE (AChE-R) in photoreceptor inner segments (IS), bipolar cells, and ganglion cells. AChE activity increased in IS. The expressed AChE protein was a novel variant, characterized by an extended N terminus (N-AChE). Systemic administration of the orphan antisense agent, Monarsen, reduced the photic induction of mRNA for AChE-R, and of the N-AChE protein. Rats exposed to bright, damaging light and treated daily with Monarsen exhibited larger ERG responses, relatively thicker outer nuclear layer (ONL), and more ONL nuclei than did rats exposed to the same damaging light but treated daily with saline.


CONCLUSIONS
The findings indicate that the photic-induced novel variant of AChE (N-AChE-R) may be causally involved with retinal light damage and suggest the use of RNA targeting for limiting such damage.
Kehat
Rinat
R
Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology and the Rappaport Institute, Haifa, Israel.
Zemel
Esther
E
Cuenca
Nicolas
N
Evron
Tama
T
Toiber
Debra
D
Loewenstein
Anat
A
Soreq
Hermona
H
Perlman
Ido
I
D000110:Acetylcholinesterase / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D016923:Cell Death; D016373:DNA, Antisense / Q000494:pharmacology; D004596:Electroretinography / Q000528:radiation effects; D019084:Fluorescent Antibody Technique, Indirect; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000378:metabolism; D008027:Light; D008297:Male; D018613:Microscopy, Confocal; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000528:radiation effects*; D012162:Retinal Degeneration / Q000201:enzymology* / Q000473:pathology
D016373:DNA, Antisense; D007527:Isoenzymes; D012333:RNA, Messenger; D000110:Acetylcholinesterase