The effect of caspase inhibitors and neurotrophic factors on damaged retinal ganglion cells.
To elucidate the role of caspase inhibitors and neurotrophic factors in retinal ganglion cell (RGC) death and regeneration, we cultured mouse retinal explants in the presence of caspase-1, -3, -8, or -9 inhibitors, brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) in serum-free culture media. We quantified apoptosis by TUNEL staining in RGCs and assessed the number of regenerating neurites. Apoptosis of RGCs treated with all caspase inhibitors or with neurotrophic factors was significantly reduced and the number of regenerating neurites was significantly greater than controls (p < 0.05). Our findings indicate that caspase-1, -3, -8, -9 play a critical role in explanted RGC death and may be ideal targets of neuroprotection and regeneration of damaged RGCs.
Oshitari
Toshiyuki
T
Department of Ophthalmology and Visual Science, Graduate School of Medicine, Chiba University, Japan. tarii@aol.com
Adachi-Usami
Emiko
E
D000818:Animals; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D016501:Neurites / Q000187:drug effects / Q000201:enzymology; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology
D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D009414:Nerve Growth Factors; D020169:Caspases