Astrocyte-derived CNTF switches mature RGCs to a regenerative state following inflammatory stimulation

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.

All latest news from the category: Health and Medicine

This subject area encompasses research and studies in the field of human medicine.

Among the wide-ranging list of topics covered here are anesthesiology, anatomy, surgery, human genetics, hygiene and environmental medicine, internal medicine, neurology, pharmacology, physiology, urology and dental medicine.

Back to home

Comments (0)

Write a comment

Newest articles

New anti-cancer agent works without oxygen

Why tumors shrink but don’t disappear. “As tumors grow very quickly, consume a lot of oxygen and their vascular growth can’t necessarily keep pace, they often contain areas that are…

First blueprint of the human spliceosome revealed

Researchers detail the inner workings of the most complex and intricate molecular machine in human biology. Researchers at the Centre for Genomic Regulation (CRG) in Barcelona have created the first…

A paper-aluminum combo for strong, sustainable packaging

Takeout containers get your favorite noodles from the restaurant to your dining table (or couch) without incident, but they are nearly impossible to recycle if they are made from foil-lined…