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AIM: To investigate the expression changes of MMP-12 during the long-term axon regeneration induced by the lens injury after the optic nerve clamp trauma in sprague-dawley(SD)rats.METHODS: The optic nerve injury model and lens injury model of SD rats were established, and the 24 experimental animals were divided into control group; lens injury group; optic nerve injury group; lens injury combined with optic nerve injury group, with 6 rats in each group. Reference transcriptome sequencing was used to analyze the expression changes of differentially expressed genes in the injured optic nerve region, and relevant differentially expressed genes with high expression were screened. Quantitative real-time polymerase chain reaction(qRT-PCR)and enzyme-linked immunosorbent assay(ELISA)were used to quantify the expression changes of matrix metalloproteinase-12(MMP-12)in the injured optic nerve region.RESULTS: The Principal Component Analysis of transcriptome sequencing indicated that lens injury combined with optic nerve injury was the principal component of gene expression change. Analysis of gene expression differences showed that the expression of MMP-12 gene was up-regulated in the lens injury combined with optic nerve injury group. The mRNA expression level of MMP-12 in the lens injury combined optic nerve injury group was up-regulated compared with the control group, the optic nerve injury group and the lens injury group at 14d and 21d after successful modeling(P<0.05). At 7, 28d, there was no difference in expression among all groups. The protein expression level of MMP-12 in the lens injury combined with optic nerve injury group was up-regulated compared with the control group and optic nerve injury group at 7, 14 and 21d after successful modeling(P<0.05), and it was up-regulated in the lens injury group combined with optic nerve injury group compared with optic nerve injury group at 21d(P<0.05). At 28d, there was no difference in expression among all groups.CONCLUSION: The up-regulated expression of MMP-12 may be involved in the long-term regeneration of the optic nerve after lens injury.
ABSTRACT
@#Zebrafish has become a popular model for the study of ocular degenerative diseases due to its similarity with human visual system and its great potential of retinal regeneration. The degenerative diseases, especially retinal degeneration and optic nerve degeneration, can seriously affect visual acuity, also the regeneration and repair are very limited, which can lead to blindness in severe cases. In contrast to mammals, zebrafish can repair optic nerve axon damage and stimulate retinal Müller glial cells to differentiate into multifunctional progenitor cells, thereby, regenerating retinal neurons and nerve axons and restoring normal visual function. This review focuses on the application of zebrafish model in eye diseases and the key signaling pathways of zebrafish retinal neurons and Müller glial cells to initiate regeneration and repair in response to injury.
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Oncomodulin (OM) is known by us progressively as a Calcium binding protein.Recently, OM has been found that it is secreted by inflammatory cells (neutrophilic granulocyte), and a signal which can promote cell growth between innate immunity and neurons, and a key to regenerate the damaged optical nerves by activating inflammation.The function of promoting the regeneration progress of axons has become a hot issue in recent years.This article summarized the mechanism of OM and the relationship between inflammation-induced OM and optic nerve regeneration research and progress were reviewed.
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Glaucoma,optical neuritis and trauma are optic nerve injury-related diseases.These ocular diseases cause irreversible damage of the vision and even blindness.The study on optic nerve regeneration is a powerful approach for rescuing vision and improving the quality of life of patients.Therefore,how to promote optic nerve regeneration is always the focus in ophthalmology.In recent years,great progression has achieved by modulation of cellular signal pathway,usage of glial cells,stem cells and neurotrophic factor,etc,which lays a basis for the treatment of optic nerve injury.Ophthalmologist should trace and participate in these researches to promote the development of regeneration medicine.This review summarizes these new approaches after discussing factors effecting optic nerve regeneration briefly and proposes questions to answer.
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Lots of blinding diseases are caused by retinal ganglion cells apoptosis, but there is no the effective and ideal therapy in clinic currently. Recent study showed that stem cells can be an alternative renewable source of retinal ganglion cells, and they may be potential to repair the visual function. These results provide a new model of optic nerve regeneration for the treatment of these blinding diseases. But, some problems in clinical applications are waiting for further solving. Applications of stem cells in optic nerve regeneration is reviewed in this paper.