Translational lipidomics in glaucoma: mechanisms, biomarkers, and therapeutic horizons
- 1Schulich School of Medicine & Dentistry, Western University
- 2Department of Ophthalmology & Vision Sciences, University of Toronto
- 3Donald K. Johnson Eye Institute, University Health Network
Abstract
Glaucoma is a multifactorial optic neuropathy. Intraocular pressure (IOP), aging, vascular dysregulation, oxidative stress, mitochondrial failure, and chronic neuroinflammation converge on retinal ganglion cell (RGC) degeneration and optic nerve damage. Lipid mediators are central to this biology, linking membrane remodeling to aqueous humor (AH) dynamics, glial activation, vascular tone, extracellular matrix turnover, and neuronal survival. Lipidomics has widened the field beyond prostaglandin pharmacology to include oxylipins, lysophospholipids, sphingolipids, endocannabinoids, and specialized pro-resolving mediators (SPMs). Human studies in AH, tears, and plasma report reproducible perturbations in arachidonic acid (AA) metabolism, oxidized linoleate products, phosphatidylcholines, lysophosphatidylcholines, sphingomyelins, and ceramides; experimental models further implicate ceramide accumulation, phospholipase A2 activation, cyclooxygenase signaling, endocannabinoid tone, and failed inflammation resolution in retinal injury. Recent work also shows that latanoprost itself induces an aqueous-humor AA/LXA ₄ circuit in glaucoma patients, indicating that established prostaglandin therapy may engage endogenous resolution pathways and complicate the interpretation of treated-cohort lipidomic studies. This review covers the mechanistic roles of lipid mediators in IOP regulation, TM dysfunction, neuroinflammation, and neurodegeneration; the emerging biomarker literature in AH, tears, and plasma; and potential therapeutic directions, including soluble epoxide hydrolase (sEH) inhibition, sphingolipid modulation, endocannabinoid augmentation, and SPM-based neuroprotection. We conclude with the main barriers to translation: small ocular sample volumes, treatment confounding, limited longitudinal data, and the need for disease-subtype stratification.
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BibTeX
@article{butt2026translational,
title = {{Translational lipidomics in glaucoma: mechanisms, biomarkers, and therapeutic horizons}},
author = {Abu Bakar Butt and Michael Balas and Jeremy M. Sivak and David J. Mathew},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1921097},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1921097/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Translational lipidomics in glaucoma: mechanisms, biomarkers, and therapeutic horizons
AU - Abu Bakar Butt
AU - Michael Balas
AU - Jeremy M. Sivak
AU - David J. Mathew
PY - 2026
DA - 2026/10/26
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1921097
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1921097/full
AB - Glaucoma is a multifactorial optic neuropathy. Intraocular pressure (IOP), aging, vascular dysregulation, oxidative stress, mitochondrial failure, and chronic neuroinflammation converge on retinal ganglion cell (RGC) degeneration and optic nerve damage. Lipid mediators are central to this biology, linking membrane remodeling to aqueous humor (AH) dynamics, glial activation, vascular tone, extracellular matrix turnover, and neuronal survival. Lipidomics has widened the field beyond prostaglandin pharmacology to include oxylipins, lysophospholipids, sphingolipids, endocannabinoids, and specialized pro-resolving mediators (SPMs). Human studies in AH, tears, and plasma report reproducible perturbations in arachidonic acid (AA) metabolism, oxidized linoleate products, phosphatidylcholines, lysophosphatidylcholines, sphingomyelins, and ceramides; experimental models further implicate ceramide accumulation, phospholipase A2 activation, cyclooxygenase signaling, endocannabinoid tone, and failed inflammation resolution in retinal injury. Recent work also shows that latanoprost itself induces an aqueous-humor AA/LXA ₄ circuit in glaucoma patients, indicating that established prostaglandin therapy may engage endogenous resolution pathways and complicate the interpretation of treated-cohort lipidomic studies. This review covers the mechanistic roles of lipid mediators in IOP regulation, TM dysfunction, neuroinflammation, and neurodegeneration; the emerging biomarker literature in AH, tears, and plasma; and potential therapeutic directions, including soluble epoxide hydrolase (sEH) inhibition, sphingolipid modulation, endocannabinoid augmentation, and SPM-based neuroprotection. We conclude with the main barriers to translation: small ocular sample volumes, treatment confounding, limited longitudinal data, and the need for disease-subtype stratification.
SN - 1663-9812
ER -