Effects of GDNF on retinal ganglion cell survival following axotomy.
Recent evidence suggests that approximately 90% of retinal ganglion cells (RGCs) die by the process of apoptosis within 14 days of optic nerve transection. RGCs begin to disappear from the retina between 5 and 7 days postaxotomy when the highest percentage of RGCs show characteristics typical of apoptosis. A single intraocular injection of glial cell-line derived neurotrophic factor (GDNF) given at the time of axotomy resulted in a delay in the initiation of RGC death and increased the densities of surviving RGCs at 7, 10 and 14 days postaxotomy. The mean RGC densities in GDNF treated retinas at 7 (2381 +/- 144), 10 (1561 +/- 117) and 14 (1123 +/- 116) days postaxotomy were significantly higher than that of controls (1835 +/- 82, 835 +/- 272 and 485 +/- 39, respectively). The loss of RGCs was paralleled by increases in TUNEL positive staining in control retinas and a lower percentage of TUNEL positive cells in GDNF treated retinas at 5, 7 and 10 days postaxotomy. These results suggest that GDNF is capable of promoting RGC survival following injury, possibly by interfering with an essential step in apoptosis.
Department of Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
P D
PD
Koeberle
A K
AK
Ball
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019771:Axotomy; D002452:Cell Count; D002470:Cell Survival; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018613:Microscopy, Confocal; D009414:Nerve Growth Factors / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009900:Optic Nerve / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology*; D013997:Time Factors
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins