title: 670-nm light treatment reduces complement propagation following retinal degeneration.
abstract: OBJECTIVE
  Complement activation is associated with the pathogenesis of age-related macular degeneration (AMD). We aimed to investigate whether 670-nm light treatment reduces the propagation of complement in a light-induced model of atrophic AMD.
  
  
  METHODS
  Sprague-Dawley (SD) rats were pretreated with 9 J/cm(2) 670-nm light for 3 minutes daily over 5 days; other animals were sham treated. Animals were exposed to white light (1,000 lux) for 24 h, after which animals were kept in dim light (5 lux) for 7 days. Expression of complement genes was assessed by quantitative polymerase chain reaction (qPCR), and immunohistochemistry. Counts were made of C3-expressing monocytes/microglia using in situ hybridization. Photoreceptor death was also assessed using outer nuclear layer (ONL) thickness measurements, and oxidative stress using immunohistochemistry for 4-hydroxynonenal (4-HNE).
  
  
  RESULTS
  Following light damage, retinas pretreated with 670-nm light had reduced immunoreactivity for the oxidative damage maker 4-HNE in the ONL and outer segments, compared to controls. In conjunction, there was significant reduction in retinal expression of complement genes C1s, C2, C3, C4b, C3aR1, and C5r1 following 670 nm treatment. In situ hybridization, coupled with immunoreactivity for the marker ionized calcium binding adaptor molecule 1 (IBA1), revealed that C3 is expressed by infiltrating microglia/monocytes in subretinal space following light damage, which were significantly reduced in number after 670 nm treatment. Additionally, immunohistochemistry for C3 revealed a decrease in C3 deposition in the ONL following 670 nm treatment.
  
  
  CONCLUSIONS
  Our data indicate that 670-nm light pretreatment reduces lipid peroxidation and complement propagation in the degenerating retina. These findings have relevance to the cellular events of complement activation underling the pathogenesis of AMD, and highlight the potential of 670-nm light as a non-invasive anti-inflammatory therapy.
authors.affiliation: The John Curtin School of Medical Research, College of Medicine, Biology and Environment, The Australian National University, Building 131, Garran Rd, Canberra ACT 2601, Australia. matt.rutar@anu.edu.au
authors.forename: Matt
authors.initials: M
authors.lastname: Rutar
authors.forename: Riccardo
authors.initials: R
authors.lastname: Natoli
authors.forename: Rizalyn
authors.initials: R
authors.lastname: Albarracin
authors.forename: Krisztina
authors.initials: K
authors.lastname: Valter
authors.forename: Jan
authors.initials: J
authors.lastname: Provis
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D003165:Complement System Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000528:radiation effects*; D008027:Light / Q000009:adverse effects*; D008264:Macrophages / Q000378:metabolism / Q000528:radiation effects; D017628:Microglia / Q000378:metabolism / Q000528:radiation effects; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000528:radiation effects; D012333:RNA, Messenger / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D012162:Retinal Degeneration / Q000209:etiology / Q000378:metabolism / Q000473:pathology
chemical_list: D000447:Aldehydes; D012333:RNA, Messenger; D003165:Complement System Proteins; C027576:4-hydroxy-2-nonenal