title: Spatiotemporal Cadence of Macrophage Polarisation in a Model of Light-Induced Retinal Degeneration.
abstract: BACKGROUND
  The recruitment of macrophages accompanies almost every pathogenic state of the retina, and their excessive activation in the subretinal space is thought to contribute to the progression of diseases including age-related macular degeneration. Previously, we have shown that macrophages aggregate in the outer retina following damage elicited by photo-oxidative stress, and that inhibition of their recruitment reduces photoreceptor death. Here, we look for functional insight into macrophage activity in this model through the spatiotemporal interplay of macrophage polarisation over the course of degeneration.
  
  
  METHODS
  Rats were exposed to 1000 lux light damage (LD) for 24 hrs, with some left to recover for 3 and 7 days post-exposure. Expression and localisation of M1- and M2- macrophage markers was investigated in light-damaged retinas using qPCR, ELISA, flow cytometry, and immunohistochemistry.
  
  
  RESULTS
  Expression of M1- (Ccl3, Il-6, Il-12, Il-1β, TNFα) and M2- (CD206, Arg1, Igf1, Lyve1, Clec7a) related markers followed discrete profiles following light damage; up-regulation of M1 genes peaked at the early phase of cell death, while M2 genes generally exhibited more prolonged increases during the chronic phase. Moreover, Il-1β and CD206 labelled accumulations of microglia/macrophages which differed in their morphological, temporal, and spatial characteristics following light damage.
  
  
  CONCLUSIONS
  The data illustrate a dynamic shift in macrophage polarisation following light damage through a broad swathe of M1 and M2 markers. Pro-inflammatory M1 activation appears to dominate the early phase of degeneration while M2 responses appear to more heavily mark the chronic post-exposure period. While M1/M2 polarisation represents two extremes amongst a spectrum of macrophage activity, knowledge of their predominance offers insight into functional consequences of macrophage activity over the course of damage, which may inform the spatiotemporal employment of therapeutics in retinal disease.
authors.affiliation: John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia.
authors.forename: Haihan
authors.initials: H
authors.lastname: Jiao
authors.affiliation: John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia.|ANU Medical School, The Australian National University, Canberra, Australian Capital Territory, Australia.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Natoli
authors.affiliation: John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia.|ANU Medical School, The Australian National University, Canberra, Australian Capital Territory, Australia.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Valter
authors.affiliation: John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia.|ANU Medical School, The Australian National University, Canberra, Australian Capital Territory, Australia.
authors.forename: Jan M
authors.initials: JM
authors.lastname: Provis
authors.affiliation: John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia.
authors.forename: Matt
authors.initials: M
authors.lastname: Rutar
mesh_terms: D000818:Animals; D016764:Cell Polarity; D053583:Interleukin-1beta / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D008027:Light; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D008954:Models, Biological; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D012160:Retina / Q000473:pathology / Q000528:radiation effects*
chemical_list: D053583:Interleukin-1beta; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface