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.
Highlights
Chronic eye diseases such as glaucoma and optic neuritis result in progressive loss of retinal ganglion cells (RGC) and blindness (Shindler et al, 2008; Almasieh et al, 2012)
Expressed genes (DEG) cluster analysis showed that acupuncture treatment groups were clustered together and separated from optic nerve crush (ONC) control, and all the ONC groups with or without acupuncture treatments were separated from WT control group (Figure 2C)
Our previous studies showed that both traumatic and chronic neuron injury resulted in activation of PERK-eIF2α-ATF4CHOP pathway or downregulating activity of PI3K-AKT-mTOR pathways, while manipulated these pathways and reversed the injury induced changes resulted in neuroprotection and increased RGC survival (Park et al, 2008; Miao et al, 2016; Yang et al, 2016; Huang et al, 2017, 2019)
Summary
Chronic eye diseases such as glaucoma and optic neuritis result in progressive loss of retinal ganglion cells (RGC) and blindness (Shindler et al, 2008; Almasieh et al, 2012). Traumatic injury such as optic nerve crush (ONC) cause serious RGC death (Sanchez-Migallon et al, 2016). We will use ONC crush injury mouse model and RNA-seq technique to analyze retinal samples with and without optic nerve injury and screen for the upregulated and downregulated TFs 2 days after ONC injury, and identified those injury-induced genes reversed after acupuncture treatment at two different acupoints
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