Functional analysis of mesencephalic astrocyte-derived neurotrophic factor in retinal ganglion cells under oxidative stress. 2021

Ji-Ae Ko, and Kaori Komatsu, and Hideaki Okumichi, and Yoshiaki Kiuchi
Department of Ophthalmology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.

Glaucoma is optic neuropathy that is characterized by progressive neurodegeneration of the retinal ganglion cells (RGCs) and axons. This condition will lead to visual impairment and bring glaucoma to become the second cause of blindness globally. Neuroprotection in glaucoma is needed to prevent the progression of optic neuropathy. In this study, we examined the effects of the superior colliculus (SC), and mesencephalic astrocyte-derived neurotrophic factor (MANF) secreted from the SC, on RGC survival after oxidative stress. SC slices and RGCs from rats (3-day old) were co-cultured using a 3D-transwell system. In addition, primary RGCs from 4 to 5-day-old rats were cultured and treated with 100 μM hydrogen peroxide (H2 O2 ), together with stimulation by MANF. Immunoblot and immunofluorescence analyses indicated down-regulated expression levels of several survival markers of RGCs. Extension of neurites was decreased in RGCs treated with 100 μM H2 O2 . Following co-culture with SC slices, or the addition of MANF, we found that both the down-regulated expression of neural markers and extension of neurites caused by oxidative stress in RGCs were blocked. Furthermore, we found a decrease in the expression of neural markers and extension of neurites after co-culture with MANF siRNA-treated SC slices compared with slices treated with mock siRNA, but, RGCs co-cultured with SC slices treated with MANF siRNA displayed no-changed about to apoptosis. These results suggest that MANF secreted from the SC may play an important role in maintenance of function and survival of RGCs. It is also possible that MANF is an important factor in neuroprotection of RGCs. SIGNIFICANCE OF THE STUDY: Glaucoma is a progressive neurodegenerative disease of the retinal ganglion cell (RGC) and their axons. Neuroprotection is aimed at protecting those neurons that are damaged glaucomatous optic neuropathy. We have now examined the effects of superior colliculus, or msencephalic astrocyte-derived neutrophic factor (MANF), secreted from superior colliculus, on RGC survival using co-culture system. Our results suggested that MANF may important key factor in neuroprotection of RGC.

UI MeSH Term Description Entries
D009414 Nerve Growth Factors Factors which enhance the growth potentialities of sensory and sympathetic nerve cells. Neurite Outgrowth Factor,Neurite Outgrowth Factors,Neuronal Growth-Associated Protein,Neuronotrophic Factor,Neurotrophic Factor,Neurotrophic Factors,Neurotrophin,Neurotrophins,Growth-Associated Proteins, Neuronal,Neuronal Growth-Associated Proteins,Neuronotrophic Factors,Neurotrophic Protein,Neurotrophic Proteins,Proteins, Neuronal Growth-Associated,Factor, Neurite Outgrowth,Factor, Neuronotrophic,Factor, Neurotrophic,Factors, Nerve Growth,Factors, Neurite Outgrowth,Factors, Neuronotrophic,Factors, Neurotrophic,Growth Associated Proteins, Neuronal,Growth-Associated Protein, Neuronal,Neuronal Growth Associated Protein,Neuronal Growth Associated Proteins,Outgrowth Factor, Neurite,Outgrowth Factors, Neurite,Protein, Neuronal Growth-Associated
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D005901 Glaucoma An ocular disease, occurring in many forms, having as its primary characteristics an unstable or a sustained increase in the intraocular pressure which the eye cannot withstand without damage to its structure or impairment of its function. The consequences of the increased pressure may be manifested in a variety of symptoms, depending upon type and severity, such as excavation of the optic disk, hardness of the eyeball, corneal anesthesia, reduced visual acuity, seeing of colored halos around lights, disturbed dark adaptation, visual field defects, and headaches. (Dictionary of Visual Science, 4th ed) Glaucomas
D006861 Hydrogen Peroxide A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. Hydrogen Peroxide (H2O2),Hydroperoxide,Oxydol,Perhydrol,Superoxol,Peroxide, Hydrogen
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012165 Retinal Ganglion Cells Neurons of the innermost layer of the retina, the internal plexiform layer. They are of variable sizes and shapes, and their axons project via the OPTIC NERVE to the brain. A small subset of these cells act as photoreceptors with projections to the SUPRACHIASMATIC NUCLEUS, the center for regulating CIRCADIAN RHYTHM. Cell, Retinal Ganglion,Cells, Retinal Ganglion,Ganglion Cell, Retinal,Ganglion Cells, Retinal,Retinal Ganglion Cell
D016501 Neurites In tissue culture, hairlike projections of neurons stimulated by growth factors and other molecules. These projections may go on to form a branched tree of dendrites or a single axon or they may be reabsorbed at a later stage of development. "Neurite" may refer to any filamentous or pointed outgrowth of an embryonal or tissue-culture neural cell. Neurite
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D018384 Oxidative Stress A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). Anti-oxidative Stress,Antioxidative Stress,DNA Oxidative Damage,Nitro-Oxidative Stress,Oxidative Cleavage,Oxidative DNA Damage,Oxidative Damage,Oxidative Injury,Oxidative Nitrative Stress,Oxidative Stress Injury,Oxidative and Nitrosative Stress,Stress, Oxidative,Anti oxidative Stress,Anti-oxidative Stresses,Antioxidative Stresses,Cleavage, Oxidative,DNA Damage, Oxidative,DNA Oxidative Damages,Damage, DNA Oxidative,Damage, Oxidative,Damage, Oxidative DNA,Injury, Oxidative,Injury, Oxidative Stress,Nitrative Stress, Oxidative,Nitro Oxidative Stress,Nitro-Oxidative Stresses,Oxidative Cleavages,Oxidative DNA Damages,Oxidative Damage, DNA,Oxidative Damages,Oxidative Injuries,Oxidative Nitrative Stresses,Oxidative Stress Injuries,Oxidative Stresses,Stress Injury, Oxidative,Stress, Anti-oxidative,Stress, Antioxidative,Stress, Nitro-Oxidative,Stress, Oxidative Nitrative,Stresses, Nitro-Oxidative

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