Dataset Information

Acupuncture Treatment Reverses Retinal Gene Expression Induced by Optic Nerve Injury via RNA Sequencing Analysis.

ABSTRACT: Glaucoma and traumatic optic nerve crush (ONC) injury result in progressive loss of retinal ganglion cells (RGCs) and defects in visual function. In clinical trials of Traditional Chinese Medicine, acupuncture has been widely used for the treatment of ocular diseases. However, the molecular mechanisms of acupuncture treatment are still unclear. In this study, we used technique of RNA sequencing (RNA-seq) to study the effects of acupuncture treatment on retinal transcriptome after axotomy injury. RNA-seq results revealed that 436 genes including 31 transcription factors (TFs) were changed after injury, among them were many well-known neural degeneration related TFs such as Jun, Ddit3, Atf3, and Atf4. Interestingly, acupuncture treatment at acupoint GB20 (Fengchi) significantly reversed a series of differential expressed genes (DEGs) induced by optic nerve injury. While treatments at BL1 (Jingming) or GB20 sham control acupoint-GV16 (Fengfu), led to limited DEG reversal. In contrast, treatments at these two sites further enhanced the trend of DEG expression induced by axotomy injury. At last, retina immunostaining results revealed that only GB20 acupoint treatment increased RGC survival, in consistent with RNA-seq results. Therefore, our study first reported that acupuncture treatment regulated retinal transcriptome and reversed the gene expression induced by axotomy injury, and GB20 acupoint treatment increased RGC survival, which will provide novel therapeutic targets for treatment of ocular diseases.

SUBMITTER: Chen J

PROVIDER: S-EPMC6808026 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Acupuncture Treatment Reverses Retinal Gene Expression Induced by Optic Nerve Injury via RNA Sequencing Analysis.

Chen Jie J Zhang Li L Liu Lanying L Yang Xueqin X Wu Fengzhi F Gan Xiulun X Zhang Rong R He Yinjia Y Lv Qiuyi Q Fu Haonan H Zhou Ling L Zhang Jiaxi J Liu Anming A Liu Xiaodong X Miao Linqing L

Frontiers in integrative neuroscience 20191016

Glaucoma and traumatic optic nerve crush (ONC) injury result in progressive loss of retinal ganglion cells (RGCs) and defects in visual function. In clinical trials of Traditional Chinese Medicine, acupuncture has been widely used for the treatment of ocular diseases. However, the molecular mechanisms of acupuncture treatment are still unclear. In this study, we used technique of RNA sequencing (RNA-seq) to study the effects of acupuncture treatment on retinal transcriptome after axotomy injury. ...[more]

PMID: 31680887

Similar Datasets

Project description:Glaucoma is a multifactorial neurodegenerative disease, characterized by degeneration of the retinal ganglion cells (RGCs). There has been little progress in developing efficient strategies for neuroprotection in glaucoma. We profiled the retina transcriptome of Lister Hooded rats at 2 weeks after optic nerve crush (ONC) and analyzed the data from the genomic fabric paradigm (GFP) to bring additional insights into the molecular mechanisms of the retinal remodeling after induction of RGC degeneration. GFP considers three independent characteristics for the expression of each gene: level, variability, and correlation with each other gene. Thus, the 17,657 quantified genes in our study generated a total of 155,911,310 values to analyze. This represents 8830x more data per condition than a traditional transcriptomic analysis. ONC led to a 57% reduction in RGC numbers as detected by retrograde labeling with 1,1'-dioctadecyl-3,3,3,3'-tetramethylindocarbocyanine perchlorate (DiI). We observed a higher relative expression variability after ONC. Gene expression stability was used as a measure of transcription control and disclosed a robust reduction in the number of very stably expressed genes. Predicted protein-protein interaction (PPI) analysis with STRING revealed axon and neuron projection as mostly decreased processes, consistent with RGC degeneration. Conversely, immune response PPIs were found among upregulated genes. Enrichment analysis showed that complement cascade and Notch signaling pathway, as well as oxidative stress and kit receptor pathway were affected after ONC. To expand our studies of altered molecular pathways, we examined the pairwise coordination of gene expressions within each pathway and within the entire transcriptome using Pearson correlations. ONC increased the number of synergistically coordinated pairs of genes and the number of similar profiles mainly in complement cascade and Notch signaling pathway. This deep bioinformatic study provided novel insights beyond the regulation of individual gene expression and disclosed changes in the control of expression of complement cascade and Notch signaling functional pathways that may be relevant for both RGC degeneration and remodeling of the retinal tissue after ONC.

Project description:Background: Low-intensity pulsed ultrasound (LIPUS) has been used in clinical studies. But little is known about its effects on the central nervous system (CNS), or its mechanism of action. Retinal ganglion cells (RGCs) are CNS neuronal cells that can be utilized as a classic model system to evaluate outcomes of LIPUS protection from external trauma-induced retinal injury. In this study, we aim to: (1) determine the pulse energy and the capability of LIPUS in RGC viability, (2) ascertain the protective role of LIPUS in optic nerve (ON) crush-induced retinal injury, and 3) explore the cellular mechanisms of RGC apoptosis prevention by LIPUS. Methods: An ON crush model was set up to induce RGC death. LIPUS was used to treat mice eyes daily, and the retina samples were dissected for immunostaining and Western blot. The expression of yes-associated protein (YAP) and apoptosis-related proteins was detected by immunostaining and Western blot in vitro and in vivo. Apoptosis of RGCs was evaluated by TUNEL staining, the survival of RGCs and retained axons were labeled by Fluoro-gold and Tuj1 antibody, respectively. Rotenone was used to set up an in vitro cellular degenerative model and siYAP was used to interfering the expression of YAP to detect the LIPUS protective function. Results: LIPUS protected RGC from loss and apoptosis in vivo and in vitro. The ratio of cleaved/pro-caspase3 also decreased significantly under LIPUS treatment. As a cellular mechanical sensor, YAP expression increased and YAP translocated to nucleus in LIPUS stimulation group, however, phospho-YAP was found to be decreased. When YAP was inhibited, the LIPUS could not protect RGC from caspase3-dependent apoptosis. Conclusion: LIPUS prevented RGCs from apoptosis in an ON crush model and in vitro cellular degenerative model, which indicates a potential treatment for further traumatic ON injury. The mechanism of protection is dependent on YAP activation and correlated with caspase-3 signaling.

Dataset Information

Acupuncture Treatment Reverses Retinal Gene Expression Induced by Optic Nerve Injury via RNA Sequencing Analysis.

Publications

Acupuncture Treatment Reverses Retinal Gene Expression Induced by Optic Nerve Injury via RNA Sequencing Analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets