Glaucoma is the leading cause of irreversible blindness worldwide. Primary open-angle glaucoma (POAG) is the most common form, and yet the cause of this disease is poorly understood. Findings from previous genome-wide association studies suggest that there is a complex metabolic network that affects optic nerve health. Researchers from Brigham and Women's Hospital, a founding member of the Mass General Brigham healthcare system, and the Department of Ophthalmology at the Icahn School of Medicine at Mount Sinai aimed to identify plasma metabolites associated with risk of developing POAG in a case-control study nested within the prospective Nurses' Health Studies and the Health Professionals Follow-Up Study. This study included 599 participants who developed POAG and 599 matched controls and examined pre-diagnostic circulating plasma metabolites from approximately 10 years before POAG diagnosis. To confirm the findings, the researchers evaluated the metabolomic data in plasma samples of 2,238 glaucoma cases and 44,723 controls from the UK Biobank. They found that higher levels of diglycerides and triglycerides were associated with risk of glaucoma, suggesting that they play an important role in glaucoma pathogenesis.
"Our study is the first to assess associations between pre-diagnostic circulating metabolites and POAG risk in two large independent datasets," said co-first authors Oana A. Zeleznik, PhD, and Jae H. Kang, ScD, investigators at Brigham's Channing Division of Network Medicine. "These results provide new insights into the etiology of POAG. Our data implicate dysregulation in lipid metabolism and mitochondrial function in glaucoma etiology and suggest new targets for glaucoma prevention or therapies," said senior author Louis R. Pasquale, MD, Professor of Ophthalmology at the Icahn School of Medicine at Mount Sinai.
