ABSTRACT
Glaucoma is a common blinding eye disease characterized by progressive loss of retinal ganglion cells （RGCs） and their axons， gradual loss of visual field， and optic atrophy. The pathological changes of glaucoma are mainly the degeneration， atrophy， and loss of RGCs and their axons， which can eventually lead to the permanent impairment of visual function. The specific pathogenesis of glaucoma remains unclear. Autophagy is a process in which damaged， denatured， or senescent proteins and organelles are transported to lysosomes for digestion and degradation in order to continuously renew and rebuild cells for reuse. As revealed by clinical case analysis and animal experiments， Chinese patent medicine and some traditional Chinese medicine （TCM） therapies may be able to target the autophagy pathway. This paper expounded the role of autophagy in glaucoma-induced ocular hypertension and optic nerve injury from the aspects of stress response of ocular tissue to high intraocular pressure， trabecular meshwork dysfunction， immune regulation， and scar regulation as well as the regulatory effects of some Chinese medicinal ingredients on autophagy， aiming to explore the possibility of integrated TCM and western medicine in regulating autophagy and preventing glaucoma-induced optic nerve injury and early visual field loss. It was found that Chinese medicinal monomers or extracts function via multiple pathways and multiple targets， mainly involving two classical autophagy pathways， namely phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） and adenosine monophosphate-activated protein kinase （AMPK）. Moreover， the current studies on the neuroprotective effect of TCM mostly focus on the brain and spinal cord lesions of the central nervous system， and its protective mechanism against optic nerve injury in glaucoma still needs further investigation. In addition， autophagy was like a "double-edged sword" in different experimental animal models and methods. How to artificially intervene in autophagy to prevent the apoptosis of RGCs and protect the optic nerve injury is still an urgent problem to be solved in the future research.
ABSTRACT
Although the transcription factor, nuclear factor-κB (NF-κB) is known to regulate cell death and survival, its precise role in cell death within the central nervous system (CNS) remains unknown. We previously reported that mice with a homozygous deficiency for NF-kBp50 spontaneously developed optic neuropathy. We examined the expression and activation of pro-opoptotic factor(s), which mediate optic neuropathy in p50-deficient (p50-/-) mice. Recombination activating gene 1 (Rag1) is known to regulate the recombination of immunoglobulin V(D)J. Experiments with genetically engineered mice revealed the involvement of Rag1 expression in the apoptosis of Brn3a-positive retinal ganglion cells (RGCs), and also showed the specific effects of a p50-deficency on the activation of Rag1 gene transcription. Furthermore, a genetic analysis of murine neuronal stem-like cells clarified the biological significance of Rag1 in NMDA (N-methyl-D-aspartat)-induced neuronal apoptosis. The apoptotic regulating factors, Bax, and cleaved caspase 3, 8, and 9 were observed in HEK293 cells expressing the external molecule of Rag1, and a human histological examination revealed the expression of Rag1 in RGCs Recent study indicated that Rag1 played a role in optic neuropathy as a pro-apoptotic candidate in p50-/- mice. This result may lead to new therapeutic targets in optic neuropathy.
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Objective To investigate the changes of retinal ganglion cells (RGCs) exposed to hypoxia and the mechanism. Methods RGCs were isolated from the retina of neonatal Long Evans rats aged 1 day and cultured, then divided into normal control group and hypoxia group (cultured in incubator containing 1 O_2, 5 CO_2 and 94 N_2). At 1, 3, 12 and 24 h after incubation, the calcium ion level by laser scanning confocal fluorescence microimaging system, the activity of SOD and the content of MDA by biochemistry technology, TNF-? by ELISA were detected. Results No changes of calcium ion level in RGCs were observed in normal control group. The calcium ion level increased significantly in the hypoxia group (P
ABSTRACT
Objective To study methylprednisolone's effect of up-regulation of Hsp27 on provocation and enhancement of self-protection and self-repair to injured central nerves,and if the injured nerves can get protection in early period,and therefore benefit injured central nerves'survival and regeneration. Methods Optic nerve axotomy was used in the experiment.The animals survived for 4,7,14,21,28 days respectively after surgery with and without MP treatment.The retinas were taken out and cut,then the number and morphological changes of RGCs with Nissl staining and the expression of Hsp27(optic density) in ganglion cell layers with immunohistochemical staining were observed respectively.The data were analysed with SAS soft ware. Results The quantity of the surviving retina ganglion cells increased in the group with high-dose intravenous methylprednisolone treatment at 7th and 14th days(P