Estrogen has a neuroprotective effect on axotomized RGCs through ERK signal transduction pathway.
The neuroprotective effects of estrogen on neuronal cells in central nervous system have been described previously, however, the mechanisms of neuroprotective effect of estrogen against retinal ganglion cell (RGC) death has not been well identified. To examine the role of endogenous sex steroids produced in ovary, retina samples were prepared from female rats with or without ovariectomy and the density of RGC was calculated. Ovariectomy alone had no effect on the density of fluorogold (FG)-labeled RGC without injury, while the density of surviving RGC after optic nerve axotomy with ovariectomy was significantly decreased compared to that without ovariectomy. To examine the role of exogenous sex steroids, 17beta-estradiol was injected into the vitreous cavity in ovariectomized rats and showed neuroprotective effect on axotomy-induced RGC death while exogenous progesterone showed no effect. Immunoblot and immunohistochemical analysis demonstrated that ERK-c-Fos signal transduction pathway was activated by exogenous 17beta-estradiol in ganglion cell layer. U0126, an ERK inhibitor, inhibited the neuroprotective effect of estrogen on axotomized RGC death. These data suggest that estrogen has neuroprotective effect through activation of ERK-c-Fos signaling pathway on axotomy-induced RGC death. The neuroprotective effect of estrogen may have therapeutic benefits in retinal diseases associated with RGC death such as glaucoma.
Nakazawa
Toru
T
Department of Ophthalmology and Visual Science, Tohoku University Graduate School of Medicine, Sendai, 980-8574 Miyagi, Japan. ntoru@fa2.so-net.ne.jp
Takahashi
Hidetoshi
H
Shimura
Masahiko
M
D000818:Animals; D019771:Axotomy; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009570:Nitriles / Q000494:pharmacology; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000201:enzymology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D002070:Butadienes; D004791:Enzyme Inhibitors; D004967:Estrogens; D018696:Neuroprotective Agents; D009570:Nitriles; C113580:U 0126; D048049:Extracellular Signal-Regulated MAP Kinases