We have recently shown that lens injury (LI) or intravitreally applied zymosan allow RGCs to survive axotomy and regenerate axons in the injured optic nerve.
Activated macrophages and oncomodulin have been suggested to be the principal mediators of this phenomenon. However, several lines of evidence show that macrophage-derived factors alone cannot account for all the beneficial effects of intraocular inflammation.
We show here that LI or zymosan induce upregulation of ciliary neurotrophic factor (CNTF) in retinal astrocytes and release CNTF independent of macrophages and activate the transcription factor signal transducers and activators of transcription 3 (STAT3) in RGCs. Levels of CNTF expressed in retinal glia and STAT3 activation in RGC were correlated with the time course of RGCs switching to an active regenerative state.
Intravitreal injections of antibodies against CNTF or a Janus-kinase inhibitor compromised the beneficial effects of LI, whereas an antiserum against oncomodulin was ineffective. Like the action of CNTF, the effects of LI were potentiated by drugs that increase intracellular cAMP levels, resulting in strong axon regeneration in vivo.
These data indicate that astrocyte-derived CNTF is a major contributor to the neuroprotective and axon-growth-promoting effects of LI and zymosan. These findings could lead to the development of a therapeutic principle for promoting axon regeneration in the CNS as a whole.
Willi Baur | idw
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Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.
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