ArticleProceedings of the National Academy of Sciences of the United States of America2017
Cytochrome P450 monooxygenase lipid metabolites are significant second messengers in the resolution of choroidal neovascularization.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 42 citations in OpenAlex.
- Dietary intake of whale oil-containing ω-3 long-chain polyunsaturated fatty acids attenuates choroidal neovascularization in mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- PDK4-mediated metabolic reprogramming is a potential therapeutic target for neovascular age-related macular degeneration.Cell death & disease · 2024Article
- Non-Neovascular Age-Related Macular Degeneration Assessment: Focus on Optical Coherence Tomography Biomarkers.Diagnostics (Basel, Switzerland) · 2024Review
- The involvement of soluble epoxide hydrolase in the development of cardiovascular diseases through epoxyeicosatrienoic acids.Frontiers in pharmacology · 2024Review
- Challenges and Opportunities in P450 Research on the Eye.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Neovascular Progression and Retinal Dysfunction in the Laser-Induced Choroidal Neovascularization Mouse Model.Biomedicines · 2023Article
- Beyond VEGF: Targeting Inflammation and Other Pathways for Treatment of Retinal Disease.The Journal of pharmacology and experimental therapeutics · 2023Review
- Decreased Expression of Soluble Epoxide Hydrolase Suppresses Murine Choroidal Neovascularization.International journal of molecular sciences · 2022Article
- Chronic exposure to traffic-related air pollution reduces lipid mediators of linoleic acid and soluble epoxide hydrolase in serum of female rats.Environmental toxicology and pharmacology · 2022Article
- Amelioration of Endotoxemia by a Synthetic Analog of Omega-3 Epoxyeicosanoids.Frontiers in immunology · 2022Article
- Long-Chain Polyunsaturated Fatty Acids and Their Metabolites Regulate Inflammation in Age-Related Macular Degeneration.Journal of inflammation research · 2022Review
- Article
- Key Role of Microglial Matrix Metalloproteinases in Choroidal Neovascularization.Frontiers in cellular neuroscience · 2021Article
- ω-3 Polyunsaturated Fatty Acids on Colonic Inflammation and Colon Cancer: Roles of Lipid-Metabolizing Enzymes Involved.Nutrients · 2020Review
- Fursultiamine Alleviates Choroidal Neovascularization by Suppressing Inflammation and Metabolic Reprogramming.Investigative ophthalmology & visual science · 2020Article
- Eicosanoids: The Overlooked Storm in Coronavirus Disease 2019 (COVID-19)?The American journal of pathology · 2020Review
- REvisiting Lipids in REtinal Diseases: A Focused Review on Age-related Macular Degeneration and Diabetic Retinopathy.Journal of lipid and atherosclerosis · 2020Review
- A Synthetic Epoxydocosapentaenoic Acid Analogue Ameliorates Cardiac Ischemia/Reperfusion Injury: The Involvement of the Sirtuin 3-NLRP3 Pathway.International journal of molecular sciences · 2020Article
- Pleiotropic Functions of Cytochrome P450 Monooxygenase-Derived Eicosanoids in Cancer.Frontiers in pharmacology · 2020Review
- Soluble epoxide hydrolase promotes astrocyte survival in retinopathy of prematurity.The Journal of clinical investigation · 2019Article
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
Abstract
Age-related macular degeneration (AMD) is the most common cause of blindness for individuals age 50 and above in the developed world. Abnormal growth of choroidal blood vessels, or choroidal neovascularization (CNV), is a hallmark of the neovascular (wet) form of advanced AMD and leads to significant vision loss. A growing body of evidence supports a strong link between neovascular disease and inflammation. Metabolites of long-chain polyunsaturated fatty acids derived from the cytochrome P450 (CYP) monooxygenase pathway serve as vital second messengers that regulate a number of hormones and growth factors involved in inflammation and vascular function. Using transgenic mice with altered CYP lipid biosynthetic pathways in a mouse model of laser-induced CNV, we characterized the role of these lipid metabolites in regulating neovascular disease. We discovered that the CYP-derived lipid metabolites epoxydocosapentaenoic acids (EDPs) and epoxyeicosatetraenoic acids (EEQs) are vital in dampening CNV severity. Specifically, overexpression of the monooxygenase CYP2C8 or genetic ablation or inhibition of the soluble epoxide hydrolase (sEH) enzyme led to increased levels of EDP and EEQ with attenuated CNV development. In contrast, when we promoted the degradation of these CYP-derived metabolites by transgenic overexpression of sEH, the protective effect against CNV was lost. We found that these molecules work in part through their ability to regulate the expression of key leukocyte adhesion molecules, on both leukocytes and endothelial cells, thereby mediating leukocyte recruitment. These results suggest that CYP lipid signaling molecules and their regulators are potential therapeutic targets in neovascular diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.