CNTF plus BDNF treatment and neuroprotective pathways in the rd1 mouse retina

被引：81

作者：

Azadi, Seifollah ^{[1
]}

Johnson, Leif E. ^{[1
]}

Paquet-Durand, Francois ^{[1
]}

Perez, Maria-Thereza R. ^{[1
]}

Zhang, Yiqin ^{[1
]}

Ekstrom, Per A. R. ^{[1
]}

van Veen, Theo ^{[1
]}

机构：

[1] Lund Univ, Dept Ophthalmol, SE-22184 Lund, Sweden

来源：

BRAIN RESEARCH | 2007年 / 1129卷 / 01期

关键词：

neurotrophic factor; photoreceptor; degeneration; rescue; signaling pathway;

D O I：

10.1016/j.brainres.2006.10.031

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The rd1 mouse is a relevant model for studying the mechanisms of photoreceptor degeneration in retinitis pigmentosa. Treatment with ciliary neurotrophic factor (CNTF) in combination with brain derived neurotrophic factor (BDNF) is known to rescue photoreceptors in cultured rd1 retinal explants. To shed light on the underlying mechanisms, we studied the effects of 9 days (starting at postnatal day 2) in vitro CNTF+BDNF treatment on the endogenous production of CNTF, BDNF, fibroblast growth factor 2 (FGF2), or the activation of extracellular signal-regulated kinase (ERK), Akt and CAMP-response-element-binding protein (CREB) in retinal explants. In rd1 explants, CNTF+BDNF decreased the number of TUNEL-positive photoreceptors. The treatment also increased endogenous rd1 levels of CNTF and BDNF, but lowered the level of FGF2 expression in rd1 explants. When wild-type explants were treated, endogenous CNTF was similarly increased, while BDNF and FGF2 levels remained unaffected. In addition, treatment of rd1 retinas strongly increased the phosphorylation of ERK, Akt and CREB. In treated wild-type explants, the same parameters were either unchanged (ERK) or decreased (Akt and CREB). The results suggest a role for Akt, ERK and CREB in conveying the neuroprotective effect of CNTF+BDNF treatment in rd1 retinal explants. (c) 2006 Elsevier B.V. All rights reserved.

引用

页码：116 / 129

页数：14

共 64 条

[11] Mechanical injury increases bFGF and CNTF mRMA expression in the mouse retina [J].