Long Noncoding RNA-Sox2OT Knockdown Alleviates Diabetes Mellitus-Induced Retinal Ganglion Cell (RGC) injury

Li, Chaopeng; Wang, Shuhong; Wang, Wenqi; Song, Shu-Guang; Liu, Xiuming

doi:10.1007/s10571-016-0380-1

Cited by 76 publications

(54 citation statements)

References 29 publications

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“…ERG alterations have been observed in streptozotocin (STZ) treated diabetic rats as early as two weeks after the onset of diabetes [55], four weeks in STZ-diabetic mice [56], and three months in the spontaneously diabetic Ins2Akita model [57]. Reduced b-wave amplitude has been reported in STZ diabetic mice, four months after the induction of diabetes [58] and in STZ-induced diabetic rats after seven weeks of diabetes [59]. The neuroprotective effect of MDL 72527 treatment in diabetes-induced retinal dysfunction is confirmed by the ERG analysis showing improved retinal function in diabetic mice.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Inhibition of Spermine Oxidase Reduces Neurodegeneration and Improves Retinal Function in Diabetic Mice

Liu

Saul

Pichavaram

et al. 2020

JCM

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Purpose Deregulation of polyamine metabolism has been implicated in various neurodegenerative disease and injury conditions. Studies from our laboratory have demonstrated that polyamine oxidation is a critical mediator of both neuronal and vascular injury in a mouse model of retinopathy of prematurity (Narayanan et al 2014; Patel et al 2016). The current study was undertaken to investigate the role of the polyamine oxidase spermine oxidase (SMO) in mediating neuronal damage and dysfunction in the diabetic retina. Methods Mice (8 weeks old, C57BL6J) were made diabetic by injection of streptozotocin (STZ, 65 mg/kg, pH 4.5, i.p.) and compared to age‐matched controls after 4 to 15 weeks of diabetes. Following the onset of hyperglycemia, mice were treated with either vehicle (normal saline) or SMO inhibitor, MDL 72527 (20 mg/kg of body weight, in saline, intra‐peritoneal, 3 times/week). Retinal neuronal function in living mice was determined by electroretinography (ERG). Retinal structure in the same mice was analyzed by Spectral Domain‐Optical Coherence Tomography (SD‐OCT). Following ERG and SD‐OCT analyses, mice were humanely euthanized, and retinas were collected and processed for immunofluorescence and western blot analyses. Results Western blot analysis showed that expression of SMO was increased in the diabetic retinas compared to controls. Inner retinal function studied by dark‐adapted electroretinography showed that the positive (pSTR) and negative (nSTR) scotopic threshold responses (measured at 110 ms and 200 ms), were significantly reduced (p<0.01, N=5–12) in the diabetic (4–12 weeks) mice as compared with the controls. The pSTR, but not the nSTR amplitudes were greatly improved in the MDL‐treated diabetic mice (p<0.05, N=5–10). The amplitude at 110 ms was dominated by the b‐wave at higher intensities and was significantly stronger in the MDL72527‐treated mice than in the vehicle‐treated diabetic mice. SD‐OCT analysis demonstrated a significant thinning of retina in the diabetic mice (p<0.01, N=5–12), which was improved in the MDL‐treated group. These data demonstrate a partial rescue of inner retinal function and retinal structure by SMO inhibition in the diabetic retina. Studies on the impact of MDL72527 treatment on neuronal survival are currently in progress. Conclusion Our results show the specific involvement of Spermine Oxidase in mediating neuronal injury in the diabetic retina and demonstrate its potential as a therapeutic target for mitigating neuronal injury in diabetic retinopathy. Support or Funding Information These studies supported by the National Eye Institute (1R01EY028569 to S.P.N) and Augusta University Culver Vision Discovery institute pilot grant to S.P.N. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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Section: Discussionmentioning

confidence: 99%

Pharmacological Inhibition of Spermine Oxidase Reduces Neurodegeneration and Improves Retinal Function in Diabetic Mice

Liu

Saul

Pichavaram

et al. 2020

JCM

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“…33, has been found to play a key role in tumorigenesis of several cancers, such as lung cancer, 13 breast cancer, 14 and hepatocellular carcinoma. 16 However, the role of Sox2ot in SCI is still largely unknown and needs to be further investigated. 16 However, the role of Sox2ot in SCI is still largely unknown and needs to be further investigated.…”

Section: Introductionmentioning

confidence: 99%

Retracted: Downregulation of long noncoding RNA Sox2ot protects PC‐12 cells from hydrogen peroxide–induced injury in spinal cord injury via regulating the miR‐211‐myeloid cell leukemia‐1 isoform2 axis

Yin

Zheng

Zhuang

et al. 2018

J of Cellular Biochemistry

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This study aimed to investigate the effects and possible mechanisms of long noncoding RNA (lncRNA) Sox2 overlapping transcript (Sox2ot) on hydrogen peroxide (H O )-induced injury in pheochromocytoma (PC-12) cells. PC-12 cells were treated with H O to cell injury. The cells were transfected with short-hairpin RNA directed against Sox2ot (sh-Sox2ot), small interfering RNA directed against myeloid cell leukemia-1 (MCL-1) isoform2 (si-MCL-1), a miR-211 mimic, a miR-211 inhibitor, and their negative controls. Under different transfected treatments, cell viability, migration, invasion, and apoptosis as well as the expressions of apoptosis- and autophagy-related proteins were investigated. Besides, the regulatory relationships between Sox2ot and miR-211, miR-211 and MCL-1, as well as between MCL-1 and the protein kinase B (Akt)/mammalian target of the rapamycin (mTOR)/p70 ribosomal S6 protein kinase (p70S6K) signaling pathway were explored. Suppression of Sox2ot inhibited H O -induced PC-12 cell injury by increasing cell viability, migration, invasion, and decreasing apoptosis and autophagy. Moreover, suppression of Sox2ot increased miR-211 expression and alleviated H O -induced injury in PC-12 cells possibly via upregulation of miR-211. Furthermore, MCL-1 isoform2 was identified as a direct target of miR-211 and could be negatively regulated by miR-211. Suppression of miR-211 aggravated H O -induced cell injury by regulation of MCL-1 isoform2. Besides, inhibition of miR-211 suppressed the activation of the Akt/mTOR/p70S6K signaling pathway in H O -treated PC-12 cells, which was reversed after knockdown of MCL-1 isoform2 at the same time. Our findings indicate that downregulation of Sox2ot may protect PC-12 cells from H O -induced injury in SCI via targeting the miR-211/MCL-1 isoform2 axis. MCL-1 isoform2 may further regulate the activation of the Akt/mTOR/p70S6K pathway to mediate H O -induced injury. The Sox2ot-miR-211-MCL-1 isoform2 axis may be a promising therapeutic strategy for SCI.

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“…Tenon's capsule fibroblast The functional interaction between lncRNA-MEG3 and Nrf2 constitutes the mechanism by which TGF-β2 induces Tenon's capsule fibroblast proliferation after glaucoma filtration surgery via the direct binding of MEG3 to Nrf2 [187] lncRNA-Sox2OT RGCs Sox2OT knockdown plays an antioxidative role via regulating Nrf2/HO-1 signaling activity [188] associated mutations that activate Nrf2 [177,178]. Also, when ROS exceeds the critical threshold, Nrf2 binds to the ARE gene of Klf9 and upregulates Klf9 expression.…”

Section: Rpesmentioning

confidence: 99%

Potential Protective and Therapeutic Roles of the Nrf2 Pathway in Ocular Diseases: An Update

Wang

Zhao

Zhang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Nuclear factor- (erythroid-derived 2-) like 2 (Nrf2) is a regulator of many processes of life, and it plays an important role in antioxidant, anti-inflammatory, and antifibrotic responses and in cancer. This review is focused on the potential mechanism of Nrf2 in the occurrence and development of ocular diseases. Also, several Nrf2 inducers, including noncoding RNAs and exogenous compounds, which control the expression of Nrf2 through different pathways, are discussed in ocular disease models and ocular cells, protecting them from dysfunctional changes. Therefore, Nrf2 might be a potential target of protecting ocular cells from various stresses and preventing ocular diseases.

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Long Noncoding RNA-Sox2OT Knockdown Alleviates Diabetes Mellitus-Induced Retinal Ganglion Cell (RGC) injury

Cited by 76 publications

References 29 publications

Pharmacological Inhibition of Spermine Oxidase Reduces Neurodegeneration and Improves Retinal Function in Diabetic Mice

Pharmacological Inhibition of Spermine Oxidase Reduces Neurodegeneration and Improves Retinal Function in Diabetic Mice

Retracted: Downregulation of long noncoding RNA Sox2ot protects PC‐12 cells from hydrogen peroxide–induced injury in spinal cord injury via regulating the miR‐211‐myeloid cell leukemia‐1 isoform2 axis

Potential Protective and Therapeutic Roles of the Nrf2 Pathway in Ocular Diseases: An Update

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