PMID- 25626968 OWN - NLM STAT- MEDLINE DCOM- 20150407 LR - 20150220 IS - 1552-5783 (Electronic) IS - 0146-0404 (Linking) VI - 56 IP - 2 DP - 2015 Jan 27 TI - Assessment of retinal function and morphology in aging Ccl2 knockout mice. PG - 1238-52 LID - 10.1167/iovs.14-15334 [doi] AB - PURPOSE: 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 Muller 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. CI - Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc. FAU - Vessey, Kirstan A AU - Vessey KA AD - Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Australia. FAU - Waugh, Michelle AU - Waugh M AD - Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Australia. FAU - Jobling, Andrew I AU - Jobling AI AD - Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Australia. FAU - Phipps, Joanna A AU - Phipps JA AD - Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Australia. FAU - Ho, Tracy AU - Ho T AD - Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Australia. FAU - Trogrlic, Lidia AU - Trogrlic L AD - Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Australia. FAU - Greferath, Ursula AU - Greferath U AD - Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Australia. FAU - Fletcher, Erica L AU - Fletcher EL AD - Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Australia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150127 PL - United States TA - Invest Ophthalmol Vis Sci JT - Investigative ophthalmology & visual science JID - 7703701 RN - 0 (Chemokines) SB - IM MH - Aging/*physiology MH - Animals MH - Cells, Cultured MH - Chemokines/metabolism MH - Dark Adaptation MH - Disease Models, Animal MH - Electroretinography MH - Immunohistochemistry MH - Macular Degeneration/genetics/metabolism/*physiopathology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Retina/pathology/*physiopathology MH - Retinal Pigment Epithelium/metabolism/pathology/physiopathology OTO - NOTNLM OT - Muller cell OT - age-related macular degeneration (AMD) (ARMD) OT - electroretinogram (ERG) OT - glia OT - macrophage OT - microglia OT - mouse OT - oscillatory potential OT - retina OT - retinal pigment epithelium (RPE) EDAT- 2015/01/30 06:00 MHDA- 2015/04/08 06:00 CRDT- 2015/01/29 06:00 PHST- 2015/01/29 06:00 [entrez] PHST- 2015/01/30 06:00 [pubmed] PHST- 2015/04/08 06:00 [medline] AID - iovs.14-15334 [pii] AID - 10.1167/iovs.14-15334 [doi] PST - epublish SO - Invest Ophthalmol Vis Sci. 2015 Jan 27;56(2):1238-52. doi: 10.1167/iovs.14-15334.