Amardeep Singh1, Mads K Falk, Thomas V F Hviid, Torben L Sørensen. 1. Department of Ophthalmology, Clinical Eye Research Unit, Copenhagen University Hospital Roskilde and University of Copenhagen, Copenhagen, Denmark. asingh@dadlnet.dk
Abstract
OBJECTIVE: Dysregulation of retinal microglial activity has been implicated in the pathogenesis of neovascular age-related macular degeneration. Microglia activity can be regulated through the membrane protein CD200 and its corresponding receptor, the CD200 receptor (CD200R). Because both the ligand and the receptor are expressed on a broad spectrum of cell types, we set out to study the expression of CD200 and CD200R on CD11b+ monocytes, granulocytes, and subsets of T lymphocytes. DESIGN: Prospective, case-control study. PARTICIPANTS: The study population consisted of 62 patients with neovascular age-related macular degeneration (AMD) and 44 age-matched controls without AMD. METHODS: The participants were aged 60 years or older, had no history of immune dysfunction or cancer, and were not receiving immune-modulating therapy. All participants were subjected to a structured interview, and detailed retinal imaging was performed: fundus autofluorescence imaging, digital color fundoscopy, and spectral-domain optical coherence tomography. Fluorescein and indocyanine green angiography were performed in patients with suspected neovascular AMD. Visual acuity was measured in both eyes. Fresh venous blood was obtained and stained with monoclonal antibodies and analyzed using flow cytometry within 6 hours of phlebotomy. MAIN OUTCOME MEASURES: The percentage of CD11b+ monocytes, granulocytes, and CD4+/CD8+ T lymphocytes positive for CD200 or CD200R in patients and controls, respectively. RESULTS: Patients with neovascular AMD had a higher percentage of CD11b+CD200+ monocytes and CD200+ monocytes compared with controls. Multiple regression analysis revealed that the intergroup differences observed were independent of age. Moreover, an age-related increment in CD200 expression on monocytes was observed in controls with healthy eyes, but not in patients with neovascular AMD. We did not find any differences in CD200 and CD200R expression between patients with subretinal fibrosis and patients without subretinal fibrosis. CONCLUSIONS: The surface expression of CD200 on circulating CD11b+ monocytes was found to be increased in patients with neovascular AMD compared with controls with healthy eyes. This novel finding supports the notion that altered regulation of the inflammatory response plays an integral role in the pathogenesis of AMD. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
OBJECTIVE: Dysregulation of retinal microglial activity has been implicated in the pathogenesis of neovascular age-related macular degeneration. Microglia activity can be regulated through the membrane protein CD200 and its corresponding receptor, the CD200 receptor (CD200R). Because both the ligand and the receptor are expressed on a broad spectrum of cell types, we set out to study the expression of CD200 and CD200R on CD11b+ monocytes, granulocytes, and subsets of T lymphocytes. DESIGN: Prospective, case-control study. PARTICIPANTS: The study population consisted of 62 patients with neovascular age-related macular degeneration (AMD) and 44 age-matched controls without AMD. METHODS: The participants were aged 60 years or older, had no history of immune dysfunction or cancer, and were not receiving immune-modulating therapy. All participants were subjected to a structured interview, and detailed retinal imaging was performed: fundus autofluorescence imaging, digital color fundoscopy, and spectral-domain optical coherence tomography. Fluorescein and indocyanine green angiography were performed in patients with suspected neovascular AMD. Visual acuity was measured in both eyes. Fresh venous blood was obtained and stained with monoclonal antibodies and analyzed using flow cytometry within 6 hours of phlebotomy. MAIN OUTCOME MEASURES: The percentage of CD11b+ monocytes, granulocytes, and CD4+/CD8+ T lymphocytes positive for CD200 or CD200R in patients and controls, respectively. RESULTS:Patients with neovascular AMD had a higher percentage of CD11b+CD200+ monocytes and CD200+ monocytes compared with controls. Multiple regression analysis revealed that the intergroup differences observed were independent of age. Moreover, an age-related increment in CD200 expression on monocytes was observed in controls with healthy eyes, but not in patients with neovascular AMD. We did not find any differences in CD200 and CD200R expression between patients with subretinal fibrosis and patients without subretinal fibrosis. CONCLUSIONS: The surface expression of CD200 on circulating CD11b+ monocytes was found to be increased in patients with neovascular AMD compared with controls with healthy eyes. This novel finding supports the notion that altered regulation of the inflammatory response plays an integral role in the pathogenesis of AMD. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.