Abstract
Purpose :
Lipidomic changes in glaucoma have not been well defined in the literature. We aimed to identify differential lipid profiles of the mouse ocular hypertensive optic nerve compared to normotensive controls. We hypothesized that there would be significant lipid changes in the ocular hypertensive mice, particularly in cellular membrane lipid composition as the phosphatidylethanolamines and phosphatidylserines are likely to be impacted during the neurodegenerative process.
Methods :
Ocular normotensive (≤17 mm of Hg; age around 7.5 months) and hypertensive (> 18 mm of Hg; age around 8 months) DBA/2J mice were selected (n=39) by measuring intraocular pressure (IOP) using a Tonolab tonometer. The retinal thickness was measured by optical coherence tomography (OCT), and pattern electroretinograms (PERG) were obtained at least 15 days prior to euthanasia and extraction of optic nerves. Bligh and Dyer Lipid extraction was performed on harvested optic nerve tissues followed by high performance liquid chromatography- tandem Mass Spectrometry (LCMS/MS). Lipids were analyzed using LipidSearchTM 4.1 software and subjected to further bioinformatics analysis with MetaboAnalyst 4.0 software. Rigorous statistical analysis was performed.
Results :
IOP measurements, OCT and PERG analysis confirmed that optic nerves used in profiling had glaucomatous damage compared to controls. Statistical T-Test performed found 16 lipid classes with statistically significant differences out of 23 lipid classes identified between ocular normotensive and the hypertensive group (p= 0.05). Furthermore, within these 16 lipid classes, 133 lipid species out of the 399 identified showed statistically significant differences (p=0.05). Within the phospholipids, we observed decreases in phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylethanolamine (PE) and phosphatidic acid (PA) in the hypertensive optic nerves compared to controls. However, only PE and PA were found to be statistically significant (P=0.01).
Conclusions :
As we hypothesized, the phospholipids that make up the cellular membrane exhibited change. We found normotensive and hypertensive optic nerve lipid profiles to possess various degrees of statistically significant differences. The changes characterized in this study depict the effects of glaucoma at the cellular level and future analysis using a multi-omics approach may further elucidate the cellular characteristics of glaucomatous patients.
This is a 2020 ARVO Annual Meeting abstract.