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In addition to supporting neuronal survival, cytokines or their signalling pathways also play important roles in the course of neuronal death and survival. Nerve growth factor (NGF) and its high-affinity receptor (TrkA) are expressed in the rodent retina and NGF is known to provide survival signals for retinal ganglion cells (RGCs), which are the major neurons in the visual system of the retina. Here, we have further investigated the functions of NGF in the retina using NGF (or its receptor TrkA) null mice and primary retinal cell cultures and ex vivo retinal explant experiments. We found that NGF is required for protecting photoreceptors and RGCs against apoptotic cell death caused by oxidative stress induced by 6-hydroxydopamine (6-OHDA) or selenite. NGF also protects RGCs against a wide range of apoptotic stimuli, such as trophic factor withdrawal, serum deprivation, and toxicity by anti-mitotic drugs. Our data show that NGF protects RGCs by both TrkA-dependent and -independent processes. More importantly, we find that NGF acts on RGCs to regulate the balance between cell survival and death, and to promote RGC axon growth through its receptor TrkA. Our findings not only provide mechanistic insight into the neuroprotective functions of NGF, but also suggest that NGF may be a potential therapeutic agent to treat neurodegenerative diseases.5 Simple Techniques For click here
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