Retinal ganglion cells lose trophic responsiveness after axotomy.
Whereas PNS neurons in culture are intrinsically responsive to peptide trophic factors, retinal ganglion cells (RGCs) are not unless they are depolarized, or their intracellular levels of cyclic AMP (cAMP) are elevated. We show here that depolarization increases cAMP in cultured RGCs sufficiently to enhance their responsiveness and that the trophic responsiveness of developing RGCs in intact retinas depends on physiological levels of activity and cAMP elevation. Responsiveness is lost after axotomy but is restored by cAMP elevation. The death of axotomized RGCs can be prevented if they are simultaneously stimulated by several trophic factors together with cAMP elevation. Thus, the death of RGCs after axotomy is not caused solely by the loss of retrograde trophic stimuli but also by a profound loss of trophic responsiveness.
Stanford University School of Medicine, Department of Neurobiology, California 94305, USA.
S
S
Shen
A P
AP
Wiemelt
F A
FA
McMorris
B A
BA
Barres
D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D019771:Axotomy; D016923:Cell Death; D002467:Cell Nucleus / Q000201:enzymology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004594:Electrophysiology; D005455:Fluorescent Antibody Technique; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009414:Nerve Growth Factors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000502:physiology*
D000067956:Adenylyl Cyclase Inhibitors; D009414:Nerve Growth Factors; D005576:Colforsin; D000242:Cyclic AMP; D020928:Mitogen-Activated Protein Kinases