Enhanced Ccl2-Ccr2 signaling drives more severe choroidal neovascularization with aging

• Published in: Neurobiology of aging Vol. 40; pp. 110 - 119
• Main Authors: Robbie, Scott J, Georgiadis, Anastasios, Barker, Susie E, Duran, Yanai, Smith, Alexander J, Ali, Robin R, Luhmann, Ulrich F.O, Bainbridge, James W
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2016
• Subjects: Aging; Aging - genetics; Aging - pathology; Animals; CCL2; Cells, Cultured; Chemokine CCL2 - physiology; Choroid; Choroidal neovascularization; Choroidal Neovascularization - genetics; Choroidal Neovascularization - pathology; Internal Medicine; Mice, Inbred C57BL; Mice, Knockout; Myeloid cells; Neurology; Receptors, CCR2 - physiology; Retina; Severity of Illness Index; Signal Transduction; Aging; Choroid; Retina; CCL2; Myeloid cells; Choroidal neovascularization
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2015.12.019

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.