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Therapeutic Effects of PPARα Agonist on Ocular Neovascularization in Models Recapitulating Neovascular Age-Related Macular Degeneration
| Content Provider | Semantic Scholar |
|---|---|
| Author | Qiu, Fangfang Matlock, Greg Chen, Qian J. Zhou, Kelu Kevin Du, Yanhong Wang, Xiang Zhan Ma, Jian-Xing |
| Copyright Year | 2017 |
| Abstract | Purpose This study was designed to evaluate effects of fenofibric acid (Feno-FA), a peroxisome proliferator-activated receptor-alpha (PPARα) agonist, on ocular neovascularization (NV) in models recapitulating neovascular age-related macular degeneration (AMD), and to explore whether the effects are PPARα dependent. Methods Laser-induced choroidal NV (CNV) in rats and very low-density lipoprotein receptor knockout (Vldlr-/-) mice received daily intraperitoneal injections of Feno-FA or vehicle. Vascular leakage was examined by fundus fluorescein angiography and permeability assay using Evans blue as tracer. In CNV rats, severity of CNV was evaluated by CNV areas and CNV volume. In Vldlr-/- mice, subretinal NV (SRNV) and intraretinal NV (IRNV) were quantified in choroid flat mount and retina flat mount, respectively. Inflammatory factors were measured using Western blotting and retinal leukostasis assay. Further, Pparα-/- mice and age-matched wild-type (WT) mice were used for laser-induced CNV and treated with Feno-FA to explore the underlying mechanism. Results Feno-FA significantly reduced vascular leakage in CNV rats and Vldlr-/- mice, reduced CNV volume in laser-induced CNV rats, and suppressed SRNV and IRNV in Vldlr-/- mice. In addition, Feno-FA downregulated the expression of inflammatory factors, including VEGF, TNF-α, and intercellular cell adhesion molecule-1 (ICAM-1), in the eyecups of CNV rats and decreased adherent retinal leukocytes in Vldlr-/- mice. Furthermore, Pparα-/- mice developed more severe CNV compared with WT mice, and PPARα knockout abolished the beneficial effects of Feno-FA on CNV. Conclusions Feno-FA has therapeutic effects on ocular NV in models recapitulating neovascular AMD through a PPARα-dependent mechanism. |
| Starting Page | 5065 |
| Ending Page | 5075 |
| Page Count | 11 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://tvst.arvojournals.org/data/journals/iovs/936515/i1552-5783-58-12-5065.pdf?resultclick=1 |
| Alternate Webpage(s) | https://iovs.arvojournals.org/data/journals/iovs/936515/i1552-5783-58-12-5065.pdf?resultclick=1 |
| Alternate Webpage(s) | http://tvst.arvojournals.org/data/journals/iovs/936515/i1552-5783-58-12-5065.pdf?resultclick=1 |
| Alternate Webpage(s) | https://abstracts.iovs.org/data/journals/iovs/936515/i1552-5783-58-12-5065.pdf?resultclick=1 |
| Alternate Webpage(s) | http://arvojournals.org/data/journals/iovs/936515/i1552-5783-58-12-5065.pdf?resultclick=1 |
| PubMed reference number | 28980001v1 |
| Alternate Webpage(s) | https://doi.org/10.1167/iovs.17-22091 |
| DOI | 10.1167/iovs.17-22091 |
| Journal | Investigative ophthalmology & visual science |
| Volume Number | 58 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Choroid Choroidal Neovascularization Copy Number Polymorphism Evans blue Extravasation Fluorescein Angiography Folic Acid Fungal eye infections Glaucoma, Neovascular Leukostasis Lipoprotein Receptor Lipoproteins Macular degeneration Ocular Hypotension Pathologic Neovascularization Peroxisome Proliferators Retina Retinal Hemorrhage Subretinal fluid (substance) Tracer VLDLR protein, human Western Blotting angiogram fenofibric acid |
| Content Type | Text |
| Resource Type | Article |
