Temporal Alterations of Sphingolipids in Optic Nerves After Indirect Traumatic Optic Neuropathy

Muhammad Z Chauhan; Paul H Phillips; Joseph G Chacko; David B Warner; Daniel Pelaez; Sanjoy K Bhattacharya

doi:10.1016/j.xops.2022.100217

Temporal Alterations of Sphingolipids in Optic Nerves After Indirect Traumatic Optic Neuropathy

Ophthalmol Sci. 2022 Sep 7;3(1):100217. doi: 10.1016/j.xops.2022.100217. eCollection 2023 Mar.

Authors

Muhammad Z Chauhan^{1

2}, Paul H Phillips¹, Joseph G Chacko¹, David B Warner¹, Daniel Pelaez³, Sanjoy K Bhattacharya^{2

4}

Affiliations

¹ Department of Ophthalmology, Jones Eye Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
² Miami Integrative Metabolomics Research Center, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida.
³ Dr Nasser Al-Rashid Orbital Vision Research Center, Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida.
⁴ Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida.

Abstract

Purpose: To identify optic nerve (ON) lipid alterations associated with sonication-induced traumatic optic neuropathy (TON).

Design: Experimental study.

Subjects: A 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.

Methods: Analyses 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 measures: Lipid 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.

Results: There 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).

Conclusions: Temporal 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.

Keywords: CerG1, hexosylceramide; Lipid ontology; Lipidomics; ON, optic nerve; PC, principal component; PERG, pattern electroretinogram; RGC, retinal ganglion cell; SM, sphingomyelin; ST, sulfatide; Sonication-induced optic neuropathy; Sphingolipid metabolism; TON, traumatic optic neuropathy; Traumatic optic neuropathy.