title: Intense physiological light upregulates vascular endothelial growth factor and enhances choroidal neovascularization via peroxisome proliferator-activated receptor γ coactivator-1α in mice.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Ophthalmology, University of Tokyo School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. ueta-tky@umin.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Ueta
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Inoue
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yuda
authors.forename: Takahisa
authors.initials: T
authors.lastname: Furukawa
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yanagi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tamaki
mesh_terms: D000818:Animals; D002460:Cell Line; D002829:Choroid / Q000098:blood supply*; D020256:Choroidal Neovascularization / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D017930:Genes, Reporter; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008027:Light / Q000009:adverse effects*; D008268:Macular Degeneration / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010587:Phagocytosis / Q000528:radiation effects; D017440:Photoperiod; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000172:deficiency / Q000235:genetics; D055214:Retinal Photoreceptor Cell Outer Segment / Q000378:metabolism / Q000528:radiation effects; D055213:Retinal Pigment Epithelium / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D013997:Time Factors; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014162:Transfection; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D018398:Homeodomain Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D015534:Trans-Activators; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D000097983:ERRalpha Estrogen-Related Receptor; C485290:Ppargc1a protein, mouse; C467484:VEGFA protein, human; C109288:cone rod homeobox protein; C467480:vascular endothelial growth factor A, mouse