title: Enhanced Ccl2-Ccr2 signaling drives more severe choroidal neovascularization with aging.
abstract: The impact of many inflammatory diseases is influenced by age-related changes in the activation of resident and circulating myeloid cells. In the eye, a major sight-threatening consequence of age-related macular degeneration is the development of severe choroidal neovascularization (CNV). To identify the molecular pathways and myeloid cell populations involved in this increased neovascular response, we characterized the immune status of murine choroid and retina during aging and in the context of experimental CNV. In the choroid, but not in the retina, advancing age is associated with proinflammatory upregulation of CCL2-CCR2 signaling. Genetic excision of CCL2 diminishes age-related inflammatory changes in the choroid, with reduced recruitment of proinflammatory myeloid cells and attenuation of CNV. These findings indicate that CCL2-driven recruitment of myeloid cells contributes to increased severity of CNV with age. Similar mechanisms may be involved in other age-related inflammatory diseases.
authors.affiliation: Department of Genetics, UCL Institute of Ophthalmology, London, UK; NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Robbie
authors.affiliation: Department of Genetics, UCL Institute of Ophthalmology, London, UK.
authors.forename: Anastasios
authors.initials: A
authors.lastname: Georgiadis
authors.affiliation: Department of Genetics, UCL Institute of Ophthalmology, London, UK.
authors.forename: Susie E
authors.initials: SE
authors.lastname: Barker
authors.affiliation: Department of Genetics, UCL Institute of Ophthalmology, London, UK.
authors.forename: Yanai
authors.initials: Y
authors.lastname: Duran
authors.affiliation: Department of Genetics, UCL Institute of Ophthalmology, London, UK.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Smith
authors.affiliation: Department of Genetics, UCL Institute of Ophthalmology, London, UK; NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.
authors.forename: Robin R
authors.initials: RR
authors.lastname: Ali
authors.affiliation: Department of Genetics, UCL Institute of Ophthalmology, London, UK; Roche Pharmaceutical Research and Early Development, Ophthalmology Discovery and Biomarkers, Roche Innovation Center Basel, Basel, Switzerland. Electronic address: ulrich.luhmann@roche.com.
authors.forename: Ulrich F O
authors.initials: UFO
authors.lastname: Luhmann
authors.affiliation: Department of Genetics, UCL Institute of Ophthalmology, London, UK; NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK. Electronic address: j.bainbridge@ucl.ac.uk.
authors.forename: James W
authors.initials: JW
authors.lastname: Bainbridge
mesh_terms: D000375:Aging / Q000235:genetics* / Q000473:pathology*; D000818:Animals; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000502:physiology*; D020256:Choroidal Neovascularization / Q000235:genetics* / Q000473:pathology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054390:Receptors, CCR2 / Q000502:physiology*; D012720:Severity of Illness Index; D015398:Signal Transduction
chemical_list: C491768:Ccl2 protein, mouse; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D054390:Receptors, CCR2
keywords: Aging; CCL2; Choroid; Choroidal neovascularization; Myeloid cells; Retina