Analyzing data from thousands of study participants, researchers from Harvard and Icahn School of Medicine at Mount Sinai found that higher levels of two lipids, diglycerides and triglycerides, were associated with an increased risk of glaucoma. Specifically, they report that lipid metabolism is associated with primary open-angle glaucoma (POAG)—and the association was greater in cases of paracentral visual loss.1 Whether or not statins could help treat glaucoma remains unclear, said study author Louis M. Pasquale, MD, at Mount Sinai Health System.
“POAG, particularly in the subset [of people] with early paracentral loss, has a metabolic signature focused on lipid and mitochondrial metabolism,” said Dr. Pasquale, who hopes the findings shine a light on POAG pathogenesis and inform strategies that could help prevent glaucoma.
DIGLYCERIDES AND TRIGLYCERIDES. Certain lipids may play an important role in glaucoma pathogenesis.
Methodology. In this nested case-control study to identify metabolites associated with POAG, the investigators analyzed blood sample data from more than 80,000 U.S. health professionals participating in the long-term Nurses’ Health Studies and Health Professionals’ Follow-Up Study. They identified individuals who went on to develop POAG during the course of the studies. In all, 599 cases of POAG were documented and compared to 599 matched controls who did not develop glaucoma.1 Then, researchers examined data based on the metabolomic profiling of blood samples from all participants. The profiling used liquid chromatography tandem mass spectrometry to identify 369 metabolites associated with glaucoma. By comparing the metabolite profiles of individuals with POAG to those without the condition, the researchers aimed to identify potential biomarkers for glaucoma.
After adjusting for risk factors, they found that five individual lipids of the 369 metabolites demonstrated a nominal adverse association with POAG. Specifically, higher levels of diglycerides and triglycerides were associated with an increased risk of POAG (whereas higher levels of carnitines were associated with a reduced risk of POAG).
For comparison, they turned to data from the UK Biobank, in which 168 metabolites were measured using nuclear magnetic resonance spectroscopy in plasma samples from 2,238 prevalent glaucoma cases (a random subset of more than 100,000 participants) and 44,723 controls.
In all cohorts, “higher levels of diglycerides and triglycerides are adversely associated with glaucoma, suggesting that they play an important role in glaucoma pathogenesis,” the authors wrote.
“Achieving replication for our findings in the UK Biobank sets our work apart from other studies,” Dr. Pasquale said.
Surprising finding. Researchers went one step further by stratifying POAG into cases with peripheral vision loss and those with paracentral vision loss. The metabolomic signature of dysregulated lipid metabolism and mitochondrial function was more profound in patients with early paracentral visual loss compared to those with peripheral vision loss.
“This was surprising because the sample size for this subset of POAG patients was small, and the number of retinal ganglion cells affected in early paracentral loss is considerably smaller compared to the overall number of retinal ganglion cells in the retina,” Dr. Pasquale said.
Treatment. When asked about the possibility of using dyslipidemia-targeting treatments, such as statins, to lower the risk of glaucoma, Dr. Pasquale said, “The dyslipidemia we uncovered in this study is complex and is not necessarily corrected by statins, which are designed to lower LDL cholesterol.”
He also said that which lipoproteins are carrying the lipids adversely associated with POAG remain to be determined.
Study limitations. The study population had a high percentage of White participants, so the findings may not be generalizable to other populations with different race and ethnicity compositions, the authors wrote.
Looking ahead. “Our findings can help shed light on POAG pathogenesis and inform preventive strategies,” said Dr. Pasquale. But, he said, many potentially unidentified metabolite associations with POAG are unexplored.
—Christos Evangelou, PhD
1 Zeleznik OA et al. Nat Commun. 2023;14(1):2860.
Relevant financial disclosures: Dr. Pasquale—National Eye Institute: S; Research to Prevent Blindness (NYC): S; The Glaucoma Foundation: S.
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Full Financial Disclosures
Dr. Dentel None.
Dr. Shriver None.
Dr. Subramanian None.
Dr. Pasquale National Eye Institute: S; Research to Prevent Blindness (NYC): S; The Glaucoma Foundation: S; Twenty Twenty: C; Character Biosciences: C.
Dr. Yeh None.
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