Intense physiological light upregulates vascular endothelial growth factor and enhances choroidal neovascularization via peroxisome proliferator-activated receptor γ coactivator-1α in mice.
نویسندگان
چکیده
OBJECTIVE Toxicity of intense light to facilitate the development of neovascular age-related macular degeneration has been a health concern although the mechanism remains unclear. METHODS AND RESULTS Effects of intense, but within physiological range, light on retinal pigment epithelium, a major pathogenic origin of age-related macular degeneration were studied in mice. Intense physiological light upregulated vascular endothelial growth factor (VEGF) expression in retinal pigment epithelium, independent of circadian rhythm, which resulted in enhancement of choroidal neovascularization. In rd1/rd1 mice or Crx(-/-) mice that do not possess outer segment structure, light exposure did not induce VEGF, indicating that VEGF upregulation by light depended on increased outer segment phagocytosis by retinal pigment epithelium. In retinal pigment epithelium cells phagocytosing increased amount of outer segment, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) not hypoxia-inducible factor-1α was induced, leading to VEGF upregulation. The VEGF upregulation and choroidal neovascularization enhancement were abrogated in PGC-1α(-/-) mice and estrogen-related receptor-α(-/-) mice, indicating the involvement of PGC-1α/estrogen-related receptor-α pathway. CONCLUSIONS Intense physiological light is involved in choroidal neovascularization through excess outer segment phagocytosis and VEGF upregulation mediated by PGC-1α in vivo.
منابع مشابه
intense Physiological light upregulates Vascular endothelial Growth Factor and enhances choroidal Neovascularization via Peroxisome Proliferator- Activated receptor g coactivator-1a in Mice
متن کامل
Physiological light upregulates Vascular endothelial Growth Factor and enhances choroidal Neovascularization via Peroxisome Proliferator - Activated receptor g coactivator - 1 a in Mice
متن کامل
Role of peroxisome proliferator-activated receptor alpha and gamma in antiangiogenic effect of pomegranate peel extract
Objective(s): Herbal medicines are promising cancer preventive candidates. It has been shown that Punica granatum L. could inhibit angiogenesis and tumor invasion. In this study, we investigated whether the anti-angiogenic effect of pomegranate peel extract (PPE) is partly attributable to Peroxisome proliferator-activated receptors (PPARs) activation in the Human Umbilical Vein Endothelial Cell...
متن کاملNanoparticle-mediated delivery of pioglitazone enhances therapeutic neovascularization in a murine model of hindlimb ischemia.
OBJECTIVE Critical limb ischemia is a severe form of peripheral artery disease (PAD) for which neither surgical revascularization nor endovascular therapy nor current medicinal therapy has sufficient therapeutic effects. Peroxisome proliferator activated receptor-γ agonists present angiogenic activity in vitro; however, systemic administration of peroxisome proliferator-activated receptor-γ ago...
متن کاملChronic Psychological Stress Accelerates Vascular Senescence and Impairs Ischemia‐Induced Neovascularization: The Role of Dipeptidyl Peptidase‐4/Glucagon‐Like Peptide‐1‐Adiponectin Axis
BACKGROUND Exposure to psychosocial stress is a risk factor for cardiovascular disease, including vascular aging and regeneration. Given that dipeptidyl peptidase-4 (DPP4) regulates several intracellular signaling pathways associated with the glucagon-like peptide-1 (GLP-1) metabolism, we investigated the role of DPP4/GLP-1 axis in vascular senescence and ischemia-induced neovascularization in ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Arteriosclerosis, thrombosis, and vascular biology
دوره 32 6 شماره
صفحات -
تاریخ انتشار 2012