VIP-mediated increase in cAMP prevents tetrodotoxin-induced retinal ganglion cell death in vitro.
Afferent influences on natural cell death were modeled in retinal cultures derived from neonatal rats. Tetrodotoxin (TTX) blockade of electrical activity produced a significant reduction in surviving retinal ganglion cell (RGC) neurons during a critical period of development, similar in magnitude to the reduction observed during natural cell death in the intact retina at a similar developmental stage. The addition of vasoactive intestinal peptide (VIP) protected the RGCs from the lethal action of TTX. This effect was specific, since the related peptides PHI-27 and secretin produced no significant increase in RGC survival. Radioimmunoassay of cyclic nucleotides showed that TTX decreased culture levels of cAMP and that this trend was reversed by VIP. Decreases in RGC survival associated with TTX electrical blockade were prevented by 8-bromo:cAMP or forskolin. Furthermore, VIP10-28, the C-terminal fragment that inhibits VIP stimulation of adenylate cyclase, reduced the number of surviving RGCs. Thus, our results suggest that VIP, acting by increasing cAMP, has a neurotrophic effect on electrically blocked RGCs and may be an endogenous factor modulating normal cell death in the retina.
Kaiser
P K
PK
Department of Neurology, Children's Hospital, Boston, Massachusetts.
Lipton
S A
SA
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D012160:Retina / Q000187:drug effects*; D012165:Retinal Ganglion Cells / Q000187:drug effects*; D012633:Secretin / Q000494:pharmacology; D013779:Tetrodotoxin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D012633:Secretin; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; C016276:8-bromocyclic GMP; D014660:Vasoactive Intestinal Peptide; D013779:Tetrodotoxin; D000242:Cyclic AMP; D006152:Cyclic GMP