title: Assessment of retinal function and morphology in aging Ccl2 knockout mice.
abstract: OBJECTIVE
  The chemokine Ccl2, or monocyte chemoattractant protein-1 (MCP-1), has previously been identified as playing a potential role in many ocular diseases; however, its role in mice is less clear. We sought to correlate changes in retinal pigment epithelium (RPE) and retinal morphology with changes in function in aging Ccl2(-/-) mice.
  
  
  METHODS
  Ccl2(-/-) mice on a C57BL6J background were genotyped for Crb1(rd8/rd8) and were free of this mutation. Ccl2(-/-) mice and wild-type (WT) C57BL6J mice were investigated for changes in the retinal fundus and histology as a function of age. The function of the rod and cone pathways, and the rate of dark adaptation, was assessed using the electroretinogram (ERG) up to 15 months of age.
  
  
  RESULTS
  Fifteen-month-old Ccl2(-/-) mice had fundus lesions, more subretinal microglia/macrophages, and an increase in RPE cell size, indicative of RPE cell loss, when compared with WT mice. Within the retina, gross morphology was normal but there was an increase in Müller cell gliosis and microglial activation. These morphological changes in the Ccl2(-/-) RPE/retina did not correlate with a change in either rod or cone ERG pathway function, or with the rate of dark adaptation.
  
  
  CONCLUSIONS
  These data show that Ccl2 is important for preserving RPE and glial morphology with age, yet retinal function and gross morphology are maintained. Altered signaling in this chemokine pathway may, however, increase RPE and retinal vulnerability to disease.
authors: Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Australia.
authors: Kirstan A
authors: KA
authors: Vessey
authors: Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Australia.
authors: Michelle
authors: M
authors: Waugh
authors: Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Australia.
authors: Andrew I
authors: AI
authors: Jobling
authors: Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Australia.
authors: Joanna A
authors: JA
authors: Phipps
authors: Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Australia.
authors: Tracy
authors: T
authors: Ho
authors: Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Australia.
authors: Lidia
authors: L
authors: Trogrlic
authors: Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Australia.
authors: Ursula
authors: U
authors: Greferath
authors: Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Australia.
authors: Erica L
authors: EL
authors: Fletcher
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D003623:Dark Adaptation; D004195:Disease Models, Animal; D004596:Electroretinography; D007150:Immunohistochemistry; D008268:Macular Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012160:Retina / Q000473:pathology / Q000503:physiopathology*; D055213:Retinal Pigment Epithelium / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
chemical_list: D018925:Chemokines
keywords: Müller cell; age-related macular degeneration (AMD) (ARMD); electroretinogram (ERG); glia; macrophage; microglia; mouse; oscillatory potential; retina; retinal pigment epithelium (RPE)