Selective upregulation of RB3/stathmin4 by ciliary neurotrophic factor following optic nerve axotomy.
In this study, we examined the cellular responses of stathmin-related proteins in the rat retina following optic nerve (ON) axotomy. To examine the distribution of stathmin-related gene products, we performed semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), in situ hybridization (ISH) and immunohistochemical analyses. Retrograde labeling using a fluorescein tracer, fluorogold (FG), was used for the identification of retinal ganglion cells (RGCs). RT-PCR and ISH analyses indicated that the expression of RB3 was specifically increased in the ganglion cell layer (GCL) comparing to other members of stathmin-related gene family examined 3 days following the ON axotomy. When brain-derived neurotrophic factor was administrated intravitreously, the induction of RB3 mRNA sustained up to 7 days after axotomy, although the peak induction level was unchanged. In contrast, ciliary neurotrophic factor (CNTF) administration increased the peak level of RB3 mRNA induction significantly at 3 days after axotomy. Immunohistochemistry in combination with the retrograde labeling of axotomized cells by FG revealed that RB3 was increased following axotomy in FG-labeled RGCs. These data suggest that RB3 is the unique response protein in the stathmin-related proteins following ON axotomy and the induced RB3 may play a critical role in the CNTF-induced response on the axotomized RGCs, e.g. axonal regeneration and/or neuroprotection.
Nakazawa
Toru
T
Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Japan. ntoru@faz.so-net.ne.jp
Morii
Hiroshi
H
Tamai
Makoto
M
Mori
Nozomu
N
D000818:Animals; D019771:Axotomy; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002352:Carrier Proteins; D020934:Ciliary Neurotrophic Factor / Q000494:pharmacology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008565:Membrane Proteins; D008868:Microtubule Proteins; D009414:Nerve Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D009900:Optic Nerve / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects
D019208:Brain-Derived Neurotrophic Factor; D002352:Carrier Proteins; D020934:Ciliary Neurotrophic Factor; D008565:Membrane Proteins; D008868:Microtubule Proteins; D009414:Nerve Growth Factors; D012333:RNA, Messenger; C512848:Stmn2 protein, rat; C112286:Stmn4 protein, rat