Differential role of Jak-STAT signaling in retinal degenerations.
Retinal degeneration is a major cause of severe visual impairment or blindness. Understanding the underlying molecular mechanisms is a prerequisite to develop therapeutic approaches for human patients. We show in three mouse models that induced and inherited retinal degeneration induces LIF and CLC as members of the interleukin (IL)-6 family of proteins, activates proteins of the Jak-STAT signaling pathway, and up-regulates suppressors of cytokine signaling as a negative feedback loop. Inhibition of Jak2 leads to protection of photoreceptors in a model of induced but not in a model of inherited retinal degeneration. Differential activation of Akt suggests alternative pathways for cell death and/or survival in different models. Proteins induced during photoreceptor degeneration are not mainly expressed in photoreceptors but in cells of other retinal layers. This suggests a model in which photoreceptor injury is signaled to cells of the inner retina, which in turn initiate a response either to support viability or accelerate death of injured cells.
Samardzija
Marijana
M
Laboratory for Retinal Cell Biology, Department Ophthalmology, University Hospital, Frauenklinikstrasse 24, 8091 Zürich, Switzerland.
Wenzel
Andreas
A
Aufenberg
Svenja
S
Thiersch
Markus
M
Remé
Charlotte
C
Grimm
Christian
C
D000818:Animals; D017209:Apoptosis; D015850:Interleukin-6 / Q000378:metabolism; D008027:Light; D051379:Mice; D008807:Mice, Inbred BALB C; D010786:Photoreceptor Cells / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012162:Retinal Degeneration / Q000473:pathology / Q000503:physiopathology*; D050791:STAT Transcription Factors / Q000502:physiology*; D015398:Signal Transduction
D015850:Interleukin-6; D050791:STAT Transcription Factors; D011505:Protein-Tyrosine Kinases