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(Investigative Ophthalmology and Visual Science. 2005;46:2147-2155.)
© 2005 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.04-1339
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Transcorneal Electrical Stimulation Rescues Axotomized Retinal Ganglion Cells by Activating Endogenous Retinal IGF-1 System

Takeshi Morimoto,1,2,3 Tomomitsu Miyoshi,1 Satoshi Matsuda,3 Yasuo Tano,3 Takashi Fujikado,2,3 and Yutaka Fukuda1

1From the Departments of Physiology and Biosignaling, 2Visual Science, and 3Ophthalmology, Osaka University Medical School, Osaka, Japan.

PURPOSE. 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 Müller cells and then diffused into the inner retina.

CONCLUSIONS. TES can rescue the axotomized RGCs by increasing the level of IGF-1 production by Müller cells. These findings provide a new therapeutic approach to prevent or delay the degeneration of retinal neurons without the administration of exogenous neurotrophic factors.




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