STAT3 activation protects retinal ganglion cell layer neurons in response to stress

Chun Zhang, Hong Li, Mu Gen Liu, Atsushi Kawasaki, Xin Yuan Fu, Colin J. Barnstable, Samuel Shao-Min Zhang

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

STAT3 is a major signaling molecule for many neurotrophic factors but its direct role in the protection of neurons in response to stress has not been addressed. We have studied the role of STAT3 in protecting retinal neurons from damage induced by ischemia/reperfusion and glutamate excitotoxicity by using adenovirus constructs to introduce active, normal or inactive STAT3 into retinal ganglion cells in culture and cells of the ganglion cell layer in the intact retina. Transient ischemia/reperfusion was induced in adult CD1 mice by elevating the intraocular pressure to the equivalent of 120 mmHg for 60 min, followed by a return to normal pressure. The levels, activation and distribution of STAT3 protein were evaluated by Western blot and immunocytochemistry. A transient peak of STAT3 activation was seen at 24 h post ischemia and a strong increase in STAT3 protein levels 24 h later. The increase in levels of STAT3 was detected in both ganglion cell bodies and processes in the plexiform layers by immunocytochemistry. The time course of STAT3 increase was slower than the time course of ganglion cell death as measured by TUNEL assay. Intravitreal injection of NMDA led to peak increases in activated STAT3 and STAT3 at 12 and 24 h post insult respectively. Purified RGCs were infected with recombinant wild-type STAT3, constitutively active and dominant negative forms of STAT3 adenoviruses or control empty virus and then treated with glutamate. Surviving infected cells were counted 24 and 48 h later. Infection with constitutively active STAT3 gave substantial protection when compared to the other constructs. Similarly, intravitreal injection of constitutively active STAT3 adenovirus one day before ischemia-reperfusion resulted in a decreased neural cell death in the ganglion cell layer compared with GFP adenovirus control. Our results suggest that persistent activation of STAT3 by neurotrophic factors provides strong neuroprotection and will be an effective strategy in a number of chronic retinal diseases.

Original languageEnglish (US)
Pages (from-to)991-997
Number of pages7
JournalExperimental Eye Research
Volume86
Issue number6
DOIs
StatePublished - Jun 2008
Externally publishedYes

Fingerprint

Retinal Ganglion Cells
Adenoviridae
Ganglia
Ischemia
Reperfusion
Neurons
STAT3 Transcription Factor
Intravitreal Injections
Nerve Growth Factors
Glutamic Acid
Cell Death
Immunohistochemistry
Retinal Neurons
Retinal Diseases
In Situ Nick-End Labeling
N-Methylaspartate
Intraocular Pressure
Retina
Chronic Disease
Cell Culture Techniques

Keywords

  • ischemia
  • neuroprotection
  • neurotoxicity
  • retina ganglion cell layer
  • retina neurons
  • signal transduction
  • STAT3

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems

Cite this

Zhang, C., Li, H., Liu, M. G., Kawasaki, A., Fu, X. Y., Barnstable, C. J., & Shao-Min Zhang, S. (2008). STAT3 activation protects retinal ganglion cell layer neurons in response to stress. Experimental Eye Research, 86(6), 991-997. https://doi.org/10.1016/j.exer.2008.03.020

STAT3 activation protects retinal ganglion cell layer neurons in response to stress. / Zhang, Chun; Li, Hong; Liu, Mu Gen; Kawasaki, Atsushi; Fu, Xin Yuan; Barnstable, Colin J.; Shao-Min Zhang, Samuel.

In: Experimental Eye Research, Vol. 86, No. 6, 06.2008, p. 991-997.

Research output: Contribution to journalArticle

Zhang, C, Li, H, Liu, MG, Kawasaki, A, Fu, XY, Barnstable, CJ & Shao-Min Zhang, S 2008, 'STAT3 activation protects retinal ganglion cell layer neurons in response to stress', Experimental Eye Research, vol. 86, no. 6, pp. 991-997. https://doi.org/10.1016/j.exer.2008.03.020
Zhang, Chun ; Li, Hong ; Liu, Mu Gen ; Kawasaki, Atsushi ; Fu, Xin Yuan ; Barnstable, Colin J. ; Shao-Min Zhang, Samuel. / STAT3 activation protects retinal ganglion cell layer neurons in response to stress. In: Experimental Eye Research. 2008 ; Vol. 86, No. 6. pp. 991-997.
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