Objective To review the functions of these intracellular signals in their regulation of retinal ganglion cell （RGC） axon regeneration. Data sources Relevant articles published in English or Chinese from 1970 to present were selected from PubMed. Searches were made using the terms ＂intrinsic determinants, axon regeneration, RGC, optic nerve regeneration, and central nervous system axon regeneration.＂ Study selection Articles studying the mechanisms controlling RGC and central nervous system （CNS） axon regeneration were reviewed. Articles focusing on the intrinsic determinants of axon regeneration were selected. Results Like other CNS neurons of mammals, RGCs undergo a developmental loss in their ability to grow axons as they mature, which is a critical contributing factor to the failure of nerve regeneration and repair after injury. This growth failure can be attributed, at least in part, by the induction of molecular programs preventing cellular overgrowth and termination of axonal growth upon maturation. Key intracellular signals and transcription factors, including B cell lymphoma/leukemia 2, cyclic adenine monophosphate, mammalian target of rapamycin, and Kr^Jppel-like transcription factors, have been identified to play central roles in this process. Conclusions Intense effort and substantial progress have been made to identify the various intrinsic growth pathways that regulate RGC axon regeneration. More work is needed to elucidate the mechanisms of and the interrelationship between the actions of these factors and to successfully achieve regeneration and repair of the severed RGC axons.
ZHU Rui-linCHO Kin-SangGU0 Chen-yingCHEW JustinCHEN Dong-fengYANG Liu
Background Currently,no medicine is available that can prevent or treat neural damage associated with optic nerve injury.Minocycline is recently reported to have a neuroprotective function.The aims of this study were to exarmine the neuroprotective effect of minocycline on retinal ganglion cells （RGCs） and determine its underlying mechanisms,using a mouse model of optic nerve crush （ONC）.Methods ONC was performed in the left eye of adult male mice,and the mice were randomly divided into minocycline-treated group and saline-treated control group.The mice without receiving ONC injury were used as positive controls.RGC densities were assessed in retinal whole mounts with immunofluorescence labeling of βⅢ-tubulin.Transmission electron microscopy was used to detect RGC morphologies,and Western blotting and real-time PCR were applied to investigate the expression of autophagy markers LC3-Ⅰ,LC3-Ⅱ,and transcriptional factors nuclear factor-κB1 （NF-κB1）,NF-κB2.Results In the early stage after ONC （at Days 4 and 7）,the density of RGCs in the minocycline-treated group was higher than that of the saline-treated group.Electron micrographs showed that minocycline prevented nuclei and mitochondria injuries at Day 4.Western blotting analysis demonstrated that the conversion of LC3-Ⅰ to LC3-Ⅱ was reduced in the minocycline-treated group at Days 4 and 7,which meant autophagy process was inhibited by minocycline.In addition,the gene expression of NF-κB2 was upregulated by minocycline at Day 4.Conclusion The neuroprotective effect of minocycline is generated in the early stage after ONC in mice,partly through delaying autophagy process and regulating NF-κB2 pathway.
The most common irreversible blindness diseases are age-related macular degeneration, glaucoma, anddiabetic retinopathy which involve the optic nerve or retina. These diseases share a common condition of causing blindness - progressive neural cells loss of retina （photoreceptor ceils, retinal ganglion cells （RGCs））. Although many advances in the treatment for these diseases have been achieved in recent years, the visual function often cannot be reversed. To improve the visual outcomes, the retinal neuron cells must be rescued. Optic nerve diseases including glaucoma were mostly studied for the effort to rescue the injured neurons and regenerate the neuron axons.
