Mitochondrial Lipid Profiles in Traumatic Optic Neuropathy
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus Musculus
TISSUE(S): Neurons
DISEASE(S): Neuropathy
PROVIDER: ST001327 | MetabolomicsWorkbench |
REPOSITORIES: MetabolomicsWorkbench
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Project description:Traumatic optic neuropathy (TON) is a degenerative process that occurs in a subset of patients following blunt force trauma to the head. This condition is characterized by retinal ganglion cell (RGC) death and axon degeneration within the optic nerve [1]. At the cellular level, mitochondrial changes are associated with many optic neuropathies [2, 3]. Here, we provide a dataset demonstrating changes in the optic nerve mitochondrial lipid profile of a sonication-induced traumatic optic neuropathy (SI-TON) mouse model at 1, 7, and 14 days after injury. 32 C57BL/6J mice were separated into 4 groups (control, 1, 7, and 14 days) of 8, with 4 males and 4 females in each. Mice were exposed to sonication-induced trauma as described previously (by Tao et al) and optic nerves were harvested at 1, 7, or 14 days following injury [4]. Mitochondria were isolated from homogenized optic nerves and lipids were extracted. Extracted mitochondrial lipids were analysed with a Q-Exactive Orbitrap Liquid Chromatography-Mass Spectrometer (LC MS-MS). Further analysis of raw data was conducted with LipidSearch 4.1.3 and Metaboanalyst 4.0. This data is publicly available at the Metabolomics Workbench, http://www.metabolomicsworkbench.org (Project ID: PR000905).
| S-EPMC7221166 | biostudies-literature
Project description:BackgroundTraumatic optic neuropathy (TON) is an important cause of severe visual loss following blunt or penetrating head trauma. Following the initial injury, optic nerve swelling within the optic nerve canal can result in secondary retinal ganglion cell loss. Optic nerve decompression with steroids or surgical interventions or both has therefore been advocated as a means of improving visual prognosis in TON.ObjectivesThe aim of this review was to examine the effectiveness and safety of using steroids in TON.Search methodsWe searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 4), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, (January 1950 to May 2013), EMBASE (January 1980 to May 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to May 2013), Web of Science Conference Proceedings Citation Index- Science (CPCI-S) (January 1990 to May 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (http://clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 21 May 2013. We also searched the reference lists of included studies, other reviews and book chapters on TON to find references to additional trials. The Science Citation Index was used to look for papers that cited the studies included in this review. We did not manually search any journals or conference proceedings. We contacted trial investigators and experts in the field to identify additional published and unpublished studies.Selection criteriaWe planned to include only randomised controlled trials (RCTs) of TON in which any steroid regime, either on its own or in combination with surgical optic nerve decompression, was compared to surgery alone or no treatment.Data collection and analysisTwo review authors independently assessed the titles and abstracts identified from the electronic searches.Main resultsWe included one study that met our selection criteria; a double-masked, placebo-controlled, randomised trial of high dose intravenous steroids in patients with indirect TON diagnosed within seven days of the initial injury. A total of 31 eligible participants were randomised to receive either high dose intravenous steroids (n = 16) or placebo (n = 15), and they were all followed-up for three months. Mean final best corrected visual acuity (BCVA) was 1.78±1.23 Logarithm of the Minimum Angle of Resolution (LogMAR) in the placebo group, and 1.11±1.14 LogMAR in the steroid group. The mean difference in BCVA between the placebo and steroid groups was 0.67 LogMAR (95% confidence interval -1.54 to 0.20), and this difference was not statistically significant (P = 0.13). At three months follow-up, an improvement in BCVA of 0.40 LogMAR occurred in eight eyes (8/15, 53.3%) in the placebo group, and in 11 eyes (11/16, 68.8%) in the treatment group. This difference was not statistically significant (P = 0.38).Authors' conclusionsThere is a relatively high rate of spontaneous visual recovery in TON and there is no convincing data that steroids provide any additional visual benefit over observation alone. Recent evidence also suggests a possible detrimental effect of steroids in TON and further studies are urgently needed to clarify this important issue. Each case therefore needs to be assessed on an individual basis and proper informed consent is paramount.
| S-EPMC7390489 | biostudies-literature
Project description:The aim of this article is to evaluate current literature on investigation and management of traumatic optic neuropathy (TON), propose recommendations for diagnosis and management, and explore novel future treatments. TON, though uncommon, causes substantial visual loss. Without clear guidelines, there is much ambiguity regarding its diagnosis and management. Investigation and treatment (conservative, medical, surgical, and combined) vary widely between centers. Electronic databases PubMed, MEDLINE, PROSPERO, CENTRAL, and EMBASE were searched for content that matched "Traumatic optic neuropathy." Articles with abstracts and full text available, published in the past 10 years, written English and limited to human adults, were selected. All study designs were acceptable except case reports and case series with fewer 10 patients. All abstracts were then evaluated for relevance. References of these studies were evaluated and if also relevant, included. A total of 2,686 articles were retrieved and 43 examined for relevance. Of these, 23 articles were included. TON is a clinical diagnosis. Visual-evoked potential is useful in diagnosis and prognosis. Computed tomography demonstrates canal fractures and concomitant injuries. Magnetic resonance images should be reserved for select and stable patients. Conservative treatment is appropriate in mild TON. Steroids are of questionable benefit and may be harmful. Surgery should be reserved for patients with radiological evidence of compression and individualized.
| S-EPMC4329032 | biostudies-other
Project description:Messager RNA (mRNA) can be modified in a variety of ways, among which the modification of N6-methyladenosine (m6A) is one of the most common ones. Recent studies have found that the m6A modification in mRNA could functionally regulate the splicing, localization, translation, and stability of mRNA, which might be closely related to multiple diseases. However, the roles of m6A modification in traumatic optic neuropathy (TON) are unknown. Herein, we detected the expression of m6A-related genes via quantitative real-time PCR (qRT-PCR) and performed methylated RNA immunoprecipitation sequencing (MeRIP-seq) as well as RNA-sequencing to analyze the alteration profiles of m6A modification after TON. The results showed that the expression of m6A-related genes (METTL3, WTAP, FTO, and ALKBH5) were all upregulated after TON. In all, 2,810 m6A peaks were differentially upregulated and 689 m6A peaks were downregulated. In addition, the hypermethylated and hypomethylated profiles of mRNA transcripts were also identified. To sum up, our study revealed the differentially expressed m6A modification in the early stage of TON, which may provide novel insights into the mechanism and treatment of TON.
| S-EPMC7920991 | biostudies-literature
Project description:PurposeTo identify optic nerve (ON) lipid alterations associated with sonication-induced traumatic optic neuropathy (TON).DesignExperimental study.SubjectsA mouse model of indirect TON was generated using sound energy concentrated focally at the entrance of the optic canal using a laboratory sonifier with a microtip probe.MethodsAnalyses of datasets generated from high-performance liquid chromatography-electrospray tandem mass spectrometry of ONs dissected from the head of the ON to the optic chiasm at 1 day, 7 days, and 14 days postsonication compared with that in nonsonicated controls.Main outcome measuresLipid abundance alterations in postsonicated ONs were evaluated using 1-way analysis of variance (false discovery rate-adjusted significant P value < 0.01), lipid-related gene sets, biochemical properties, and receiver operating characteristic to identify lipids associated with optic neuropathy.ResultsThere were 28 lipid species with significantly different abundances across the control and postsonication groups. The 2 most significantly upregulated lipids included a sphingomyelin (SM) species, SM(d40:7), and a hexosylceramide (CerG1) species, CerG1(d18:1/24:2). Hexosylceramide (d18:1/24:2) was noted to have a stepwise increasing trend from day 1 to day 14 after sonication-induced optic neuropathy. Investigation of biophysical properties showed notable enrichment of lipids with high and above-average transition temperatures at day 14 after sonication. Lipid-related gene set analysis revealed enrichment in sphingolipid and glycosphingolipid metabolic processes. The best classifier to differentiate day 14 postsonication from controls, based on area under the receiver operating characteristic curve, was CerG1(d18:1/24:2) (area under the receiver operating characteristic curve: 1).ConclusionsTemporal alterations in sphingolipid metabolism and biochemical properties were observed in the ON of mice after sonication-induced optic neuropathy, with notable elevations in sphingomyelin and hexosylceramide species. Hexosylceramide (d18:1/24:2) may be associated with damage after indirect trauma, indicating that lipid membrane abnormalities may be a mediator of pathology due to trauma.
| S-EPMC9574713 | biostudies-literature
Project description:Background: Ethambutol-induced optic neuropathy (EON) is a well-recognized ocular complication in patients who take ethambutol as a tuberculosis treatment. The aim of the current study was to investigate the presence of mitochondrial mutations, including OPA1 and Leber's hereditary optic neuropathy (LHON)-mitochondrial DNA (mtDNA), in patients with EON and to determine their effect on clinical features of these patients. Methods: All 47 patients underwent clinical evaluations, including best-corrected visual acuity, fundus examination, and color fundus photography; 37 patients were then followed up over time. Molecular screening methods, including PCR-based sequencing of the OPA1 gene and LHON-mtDNA mutations, together with targeted exome sequencing, were used to detect mutations. Results: We detected 15 OPA1 mutations in 18 patients and two LHON-mtDNA mutations in four patients, for an overall mutation detection rate of 46.8%. The mean presentation age was significantly younger in the patients with the mitochondrial mutations (27.5 years) than in those without mutations (48 years). Fundus examination revealed a greater prevalence of optic disc hyperemia in the patients with mutations (70.5%) than without mutations (48%). Half of the patients with mutations and 91% of the patients without mutations had improved vision. After adjusting for confounders, the logistic regression revealed that the patients with optic disc pallor on the first visit (p = 0.004) or the patients with the mitochondrial mutations (p < 0.001) had a poorer vision prognosis. Conclusion: Our results indicated that carriers with OPA1 mutations might be more vulnerable for the toxicity of EMB to develop EON.
| S-EPMC8525703 | biostudies-literature
Project description:Messager RNA (mRNA) can be modified in a variety of ways, among which the modification of N6-methyladenosine (m6A) is one of the most common ones. Recent studies have found that the m6A modification in mRNA could functionally regulate the splicing, localization, translation and stability of mRNA, which might be closely related to multiple diseases. However, the roles of m6A modification in traumatic optic neuropathy (TON) are unknown. Herein, we detected the expression of m6A-related genes via quantitative real-time PCR (qRT-PCR) and performed methylated RNA immunoprecipitation sequencing (MeRIP-seq) as well as RNA-sequencing to analyze the alteration profiles of m6A modification after TON. The results showed that the expression of m6A-related genes (METTL3, WTAP, FTO and ALKBH5) were all upregulated after TON. In all, 2810 m6A peaks were differentially upregulated and 689 m6A peaks were downregulated. In addition, the hypermethylated and hypomethylated profiles of mRNA transcripts were also identified. To sum up, our study revealed the differentially expressed m6A modification in the early stage of TON, which may provide novel insights into the mechanism and treatment of TON.
2021-01-27 | GSE165520 | GEO
Project description:Traumatic optic neuropathy (TON) is the loss of vision secondary to trauma. Approximately two weeks after traumatic damage, diffuse retinal ganglion cell loss and axon degeneration of the optic nerve are exhibited [1]. Here we present the changes that occur in the optic nerve lipidome of two-month-old C57BL/6J mice following sonication-induced TON (SI-TON), which closely models the indirect clinical mechanism in TON. Optic nerves were harvested at three time points following injury: 1-day, 7-days, and 14-days for comparison with the control group (uninjured optic nerves from 2-month-old mice). The optic nerves were subjected to mass spectrometry and bioinformatic analysis using LipidSearch 4.1.3 and Metaboanalyst 4.0. This data pertains to the lipidome at each time point following indirect trauma to the optic nerve. The data presented here will augment investigation into the neurodegenerative process. The data is available at Metabolomics Workbench [http://www.metabolomicsworkbench.org (Project ID: PR000859)].
| S-EPMC6994518 | biostudies-literature
Project description: Not available
| S-EPMC6352606 | biostudies-literature
Project description:IntroductionThe treatment of traumatic optic neuropathy (TON) is highly controversial with a lack of substantiated evidence to support the use of corticosteroids or surgical decompression of the optic nerve. The aim of the study was to determine if there was a general consensus in the management of TON despite controversy in the literature.MethodsAn anonymous survey of members of the American Society of Ophthalmic Plastic and Reconstructive Surgery and the North American Neuro-Ophthalmology Society regarding their practice patterns in the management of patients with TON was performed.ResultsThe majority of 165 respondents indicated that they treated TON with corticosteroids (60%) while a significant minority (23%) performed surgical interventions (P < 0.0001). Subgroup analysis comparing rates of treatment with steroids among oculoplastic surgeons and neuro-ophthalmologists (67% vs. 47%) was not significant (Fisher's Exact test [FET], P =0.11) while results did suggest that a higher proportion of oculoplastic surgeons (33%) than neuro-ophthalmologists (11%) recommended surgical intervention (FET, P =0.004). In cases where visual acuity exhibited a downward trend treatment with steroids was the most commonly employed management. In general, neuro-ophthalmologists trended toward observation over treatment in TON patients with stable visual acuity while oculoplastic surgeons favored treatment with corticosteroids.ConclusionsIn spite of the lack of class I evidence supporting intervention of TON, the majority of respondents were inclined to offer corticosteroid treatment to patients whose visual acuity showed progressive decline following injury.
| S-EPMC8527061 | biostudies-literature