Effects of epigallocatechin-3-gallate on rat retinal ganglion cells after optic nerve axotomy.
The purpose of this study was to investigate the effects of epigallocatechin-3-gallate (EGCG) in axotomized eyes and the pathways related to its action. Wistar rats received intracranial optic nerve (ON) axotomy 2 mm behind the globe in left eyes, whereas right eyes received sham operations. EGCG was administrated via intraperitoneal injection 30 min before and 4 days after axotomy. The density of retinal ganglion cell (RGC) was examined by a retrograde labeling technique. Western blot analysis was used to assess the expression of neuronal nitric oxide synthase (nNOS), Bax, Bcl-2, ERK and Akt. Optic nerve axotomy caused 54% RGC loss 7 days following surgery, and EGCG treatment reduced RGC loss by 12% (P = 0.017). The expression of the nNOS and pro-apoptotic Bax proteins were increased 5 days after axotomy, while EGCG treatment significantly blunted the up-regulation of the above two proteins (P = 0.04 and 0.02, respectively). Axotomy-induced p-ERK 1/2 and p-Akt proteins expression 5 days and 3 days following injury, respectively. Treatment with EGCG further enhanced p-ERK 1/2 and p-Akt expressions after axotomy. Inhibition of ERK and Akt pathways attenuated the protection of EGCG on RGC against axotomy damage. Thus, we demonstrated that administration of EGCG prior to axotomy promotes RGC survival. The neuroprotective capacity of EGCG appears to act through mediating nitric oxide, anti-apoptotic, and cell survival signaling pathways.
Peng
Pai-Huei
PH
Department of Ophthalmology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
Chiou
Lan-Fen
LF
Chao
Hsiao-Ming
HM
Lin
Shan
S
Chen
Chau-Fong
CF
Liu
Jorn-Hon
JH
Ko
Mei-Lan
ML
D000818:Animals; D019771:Axotomy; D015153:Blotting, Western; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007274:Injections, Intraperitoneal; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048053:Mitogen-Activated Protein Kinase 6 / Q000037:antagonists & inhibitors / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D009900:Optic Nerve / Q000502:physiology / Q000601:surgery; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D051028:bcl-2-Associated X Protein; D002392:Catechin; C045651:epigallocatechin gallate; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D048052:Mitogen-Activated Protein Kinase 3; D048053:Mitogen-Activated Protein Kinase 6