Transcorneal electrical stimulation rescues axotomized retinal ganglion cells by activating endogenous retinal IGF-1 system.
OBJECTIVE
To investigate the effect of transcorneal electrical stimulation (TES) on the survival of axotomized RGCs and the mechanism underlying the TES-induced neuroprotection in vivo.


METHODS
Adult male Wistar rats received TES after optic nerve (ON) transection. Seven days after the ON transection, the density of the surviving RGCs was determined, to evaluate the neuroprotective effect of TES. The levels of the mRNA and protein of insulin-like growth factor (IGF)-1 in the retina after TES were determined by RT-PCR and Northern and Western blot analyses. The localization of IGF-1 protein in the retina was examined by immunohistochemistry.


RESULTS
TES after ON transection increased the survival of axotomized RGCs in vivo, and the degree of rescue depended on the strength of the electric charge. RT-PCR and Northern and Western blot analyses revealed a gradual upregulation of intrinsic IGF-1 in the retina after TES. Immunohistochemical analysis showed that IGF-1 immunoreactivity was localized initially in the endfeet of Muller cells and then diffused into the inner retina.


CONCLUSIONS
TES can rescue the axotomized RGCs by increasing the level of IGF-1 production by Muller cells. These findings provide a new therapeutic approach to prevent or delay the degeneration of retinal neurons without the administration of exogenous neurotrophic factors.
Morimoto
Takeshi
T
Department of Physiology and Biosignaling, Osaka University Medical School, Japan.
Miyoshi
Tomomitsu
T
Matsuda
Satoshi
S
Tano
Yasuo
Y
Fujikado
Takashi
T
Fukuda
Yutaka
Y
D000818:Animals; D019771:Axotomy; D015152:Blotting, Northern; D015153:Blotting, Western; D002452:Cell Count; D002470:Cell Survival / Q000502:physiology; D003315:Cornea / Q000502:physiology; D004599:Electric Stimulation Therapy / Q000379:methods*; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009900:Optic Nerve / Q000601:surgery; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I