title: Photobiomodulation Mitigates Diabetes-Induced Retinopathy by Direct and Indirect Mechanisms: Evidence from Intervention Studies in Pigmented Mice.
abstract: OBJECTIVE
  Daily application of far-red light from the onset of diabetes mitigated diabetes-induced abnormalities in retinas of albino rats. Here, we test the hypothesis that photobiomodulation (PBM) is effective in diabetic, pigmented mice, even when delayed until weeks after onset of diabetes. Direct and indirect effects of PBM on the retina also were studied.
  
  
  METHODS
  Diabetes was induced in C57Bl/6J mice using streptozotocin. Some diabetics were exposed to PBM therapy (4 min/day; 670 nm) daily. In one study, mice were diabetic for 4 weeks before initiation of PBM for an additional 10 weeks. Retinal oxidative stress, inflammation, and retinal function were measured. In some mice, heads were covered with a lead shield during PBM to prevent direct illumination of the eye, or animals were treated with an inhibitor of heme oxygenase-1. In a second study, PBM was initiated immediately after onset of diabetes, and administered daily for 2 months. These mice were examined using manganese-enhanced MRI to assess effects of PBM on transretinal calcium channel function in vivo.
  
  
  RESULTS
  PBM intervention improved diabetes-induced changes in superoxide generation, leukostasis, expression of ICAM-1, and visual performance. PBM acted in part remotely from the retina because the beneficial effects were achieved even with the head shielded from the light therapy, and because leukocyte-mediated cytotoxicity of retinal endothelial cells was less in diabetics treated with PBM. SnPP+PBM significantly reduced iNOS expression compared to PBM alone, but significantly exacerbated leukostasis. In study 2, PBM largely mitigated diabetes-induced retinal calcium channel dysfunction in all retinal layers.
  
  
  CONCLUSIONS
  PBM induces retinal protection against abnormalities induced by diabetes in pigmented animals, and even as an intervention. Beneficial effects on the retina likely are mediated by both direct and indirect mechanisms. PBM is a novel non-pharmacologic treatment strategy to inhibit early changes of diabetic retinopathy.
authors.affiliation: Case Western Reserve University, Cleveland, Ohio, United States of America; Catholic University of Brasilia, Brasilia, Brazil.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Saliba
authors.affiliation: Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Du
authors.affiliation: Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Haitao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Anatomy and Cell Biology, Wayne State University, Detroit, Michigan, United States of America.
authors.forename: Shyam
authors.initials: S
authors.lastname: Patel
authors.affiliation: Department of Anatomy and Cell Biology, Wayne State University, Detroit, Michigan, United States of America.
authors.forename: Robin
authors.initials: R
authors.lastname: Roberts
authors.affiliation: Department of Anatomy and Cell Biology, Wayne State University, Detroit, Michigan, United States of America; Department of Ophthalmology, Wayne State University, Detroit, Michigan, United States of America.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Berkowitz
authors.affiliation: Case Western Reserve University, Cleveland, Ohio, United States of America; Cleveland Veteran's Affairs Medical Center, Research Service 151, Cleveland, Ohio, United States of America.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Kern
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D028022:Low-Level Light Therapy; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D010858:Pigmentation / Q000528:radiation effects*; D011524:Protoporphyrins / Q000494:pharmacology; D012160:Retina / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects
chemical_list: D015220:Calcium Channels; D008665:Metalloporphyrins; D011524:Protoporphyrins; C032628:tin protoporphyrin IX; D051547:Heme Oxygenase-1