CNTF+BDNF treatment and neuroprotective pathways in the rd1 mouse retina.
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.
Azadi
Seifollah
S
Department of Ophthalmology, University of Lund, BMC-B13, SE-221 84 LUND, Sweden.
Johnson
Leif E
LE
Paquet-Durand
François
F
Perez
Maria-Thereza R
MT
Zhang
Yiqin
Y
Ekström
Per A R
PA
van Veen
Theo
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology* / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D020934:Ciliary Neurotrophic Factor / Q000494:pharmacology* / Q000627:therapeutic use; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004359:Drug Therapy, Combination; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008818:Mice, Neurologic Mutants; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009924:Organ Culture Techniques; D010766:Phosphorylation / Q000187:drug effects; D010786:Photoreceptor Cells / Q000187:drug effects / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000378:metabolism; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D012174:Retinitis Pigmentosa / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D020934:Ciliary Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D018696:Neuroprotective Agents; D016222:Fibroblast Growth Factor 2; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases