CNTF promotes survival of retinal ganglion cells after induction of ocular hypertension in rats: the possible involvement of STAT3 pathway.
We examined the neuroprotective effect of ciliary neurotrophic factor (CNTF) on retinal ganglion cells (RGCs) in a rat glaucoma model with increased intraocular pressure (IOP) and studied the CNTF-mediated activation of Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway. Elevated IOP was induced by laser photocoagulation of the episcleral and limbal veins. The survival of RGCs was studied using Fluoro-Gold labelled in ocular hypertensive eyes with or without CNTF intravitreal injection. Immunochemical staining and immunoblot analysis for CNTF and phosphorylated STAT3 (pSTAT3) were performed. There was a significant and progressive loss of RGCs in the retinas following the induction of elevated IOP. A single intravitreal injection of 2 microg in 2 microL CNTF significantly protected RGCs up to 4 weeks. pSTAT3 was only transiently expressed in ocular hypertensive eyes. However, in eyes treated with CNTF, pSTAT3 was observed up to 2 weeks after the induction of elevated IOP. In ocular hypertensive eyes, CNTF-positive cells were found in the inner nuclear layer (INL), and there was a transient increase in the pSTAT3 cells in the ganglion cell layer and INL. Immunoblots showed that STAT3 was transiently phosphorylated after IOP increase, but with an injection of CNTF, pSTAT3 protein was observed up to 2 weeks after hypertensive glaucoma induction. Laser-induced chronic ocular hypertension in rats resulted in the death of RGCs and a transient activation of STAT3 in the retina. Intravitreal injection of CNTF showed a significant protection of RGCs, and the JAK-STAT signalling could be one of the important pathways that underlie the mechanism of CNTF neuroprotection in this rat glaucoma model.
Ji
Jian-Zhong
JZ
Department of Anatomy, The University of Hong Kong, Hong Kong, China.
Elyaman
Wassim
W
Yip
Henry K
HK
Lee
Vincent W H
VW
Yick
Leung-Wah
LW
Hugon
Jacques
J
So
Kwok-Fai
KF
D000818:Animals; D002470:Cell Survival / Q000502:physiology; D020934:Ciliary Neurotrophic Factor / Q000502:physiology* / Q000627:therapeutic use; D004268:DNA-Binding Proteins / Q000502:physiology*; D005260:Female; D018696:Neuroprotective Agents / Q000627:therapeutic use; D009798:Ocular Hypertension / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology*
D020934:Ciliary Neurotrophic Factor; D004268:DNA-Binding Proteins; D018696:Neuroprotective Agents; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators