Immunohistochemical localization of CNTFRalpha in adult mouse retina and optic nerve following intraorbital nerve crush: evidence for the axonal loss of a trophic factor receptor after injury.
Ciliary neurotrophic factor (CNTF) is important for the survival and outgrowth of retinal ganglion cells (RGCs) in vitro. However, in vivo adult RGCs fail to regenerate and subsequently die following axotomy, even though there are high levels of CNTF in the optic nerve. To address this discrepancy, we used immunohistochemistry to analyze the expression of CNTF receptor alpha (CNTFRalpha) in mouse retina and optic nerve following intraorbital nerve crush. In normal mice, RGC perikarya and axons were intensely labeled for CNTFRalpha. At 24 hours after crush, the immunoreactivity normally seen on axons in the nerve was lost near the lesion. This loss radiated from the crush site with time. At 2 days postlesion, labeled axons were not detected in the proximal nerve, and at 2 weeks were barely detectable in the retina. In the distal nerve, loss of axonal staining progressed to the optic chiasm by 7 days and remained undetectable at 2 weeks. Interfascicular glia in the normal optic nerve were faintly labeled, but by 24 hours after crush they became intensely labeled near the lesion. Double labeling showed these to be both astrocytes and oligodendrocytes. At 7 days postlesion, darkly labeled glia were seen throughout the optic nerve, but at 14 days labeling returned to normal. It is suggested that the loss of CNTFRalpha from axons renders RGCs unresponsive to CNTF, thereby contributing to regenerative failure and death, while its appearance on glia may promote glial scarring.
Miotke
Jill A
JA
Department of Developmental and Cell Biology, University of California at Irvine, Irvine, California 92697-2305, USA. jamiotke@uci.edu
MacLennan
A John
AJ
Meyer
Ronald L
RL
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001369:Axons / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D020934:Ciliary Neurotrophic Factor / Q000378:metabolism; D053739:Ciliary Neurotrophic Factor Receptor alpha Subunit / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D005911:Gliosis / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D051379:Mice; D009410:Nerve Degeneration / Q000378:metabolism / Q000503:physiopathology; D009416:Nerve Regeneration / Q000502:physiology*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D009900:Optic Nerve / Q000378:metabolism* / Q000503:physiopathology; D020221:Optic Nerve Injuries / Q000378:metabolism* / Q000503:physiopathology; D009915:Orbit / Q000601:surgery; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D013997:Time Factors
D020934:Ciliary Neurotrophic Factor; D053739:Ciliary Neurotrophic Factor Receptor alpha Subunit