The associations of inflammation biomarkers with the risk of developing age-related macular degeneration
Epidemiology and Medical Biometry/Statistics
Final Report Abstract
Age-related macular degeneration (AMD) is one of the leading causes of blindness in the elderly in the developed world. However, the underlying pathological mechanisms of this multifactorial diseases are not yet fully understood. The recent progress in retinal imaging have allowed to precisely monitor changes of the laminar structure of the retina with an axial resolution of 5 µm in vivo. Recently, a potential role of altered gut microbiota in age-related eye diseases has been suggested. Such alterations of the gut microbiota may result in elevated blood concentrations of pathogens, antigens and pro-inflammatory molecules including lipopolysaccharide (LPS)- type endotoxins. The aim of my project was to investigate the potential associations of exposure to LPS-type endotoxins with age-related retinal diseases and morphologic changes in the Alienor cohort, a cohort of elderly French community-dwelling people, deeply phenotyped ophthalmologically. In the frame of this project, I reported a significant association between a proxy of LPS-type endotoxin exposure and incident early AMD in the Alienor cohort, suggesting that long term pro-inflammatory exposure to LPS is involved in the early pathophysiological processes of AMD. Further, I also observed a significant association between LPS and thinner peripapillary retinal nerve fiber layer, indicating an involvement of LPS in optic nerve neurodegeneration. Lastly, using longitudinal macular layer thickness data, I could also show that plasma LPS were linked with thinner baseline inner and total macular layers in the Alienor study. An additional in-depth analysis of this longitudinal morphologic data revealed that the retinal pigment epithelium – Bruch’s Membrane complex was associated with incident AMD and with genetic susceptibility to AMD. Taken together, these observations highlight the potential impact of LPS and more general of human microbiota in retinal health.
Publications
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Association of Age-Related Macular Degeneration with a Blood Biomarker of Lipopolysaccharide, a Gut Bacterial Proinflammatory Toxin. Investigative Opthalmology & Visual Science, 64(14), 47.
Larsen, Petra P.; Féart, Catherine; Pais de Barros, Jean-Paul; Merle, Benedicte M. J.; Gayraud, Laure; Delyfer, Marie-Noëlle; Korobelnik, Jean-François & Delcourt, Cécile
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Is age-related macular degeneration associated with lipopolysaccharide, a gut bacterial toxin? 23rd European Society of Retina Specialists (EURETINA) Congress, Amsterdam, Netherlands, September 2023
Larsen P.P., Féart C., Pais de Barros J.P., Merle B.M.J., Gayraud L., Delyfer M.N., Korobelnik J.F. & Delcourt C.
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Association of lipopolysaccharide, a gut bacterial toxin, with retinal neurodegeneration, Annual Meeting of the Association for research and vision in ophthalmology (ARVO), Seattle, USA, 2024
Larsen P.P., Féart C., Pais de Barros J.P., Gayraud L., Delyfer M.N., Korobelnik J.F., Schweitzer C. & Delcourt C.
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Exposure to lipopolysaccharide-type endotoxins and the aging retina, “European Eye Epidemiology” (E3) Consortium Meeting, Cambridge, UK, August 2024
Larsen P.P., Féart C., Pais de Barros J.P., Merle B.M.J., Gayraud L., Delyfer M.N., Schweitzer C., Korobelnik J.F. & Delcourt C.
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Association of Lipopolysaccharide-Type Endotoxins with Retinal Neurodegeneration: The Alienor Study. Ophthalmology Science, 5(1), 100610.
Larsen, Petra P.; Féart, Catherine; Pais de Barros, Jean-Paul; Gayraud, Laure; Delyfer, Marie-Noëlle; Korobelnik, Jean-François; Schweitzer, Cédric & Delcourt, Cécile
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Could Infectious Agents Play a Role in the Onset of Age-related Macular Degeneration? A Scoping Review. Ophthalmology Science, 5(2), 100668.
Larsen, Petra P.; Dinet, Virginie; Delcourt, Cécile; Helmer, Catherine & Linard, Morgane
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Neuroretinal and Retinal Pigment Epithelium Changes and Susceptibility to Age-Related Macular Degeneration. Ophthalmology, 132(6), 671-683.
Larsen, Petra P.; Delyfer, Marie-Noëlle; Schweitzer, Cédric; Korobelnik, Jean-François & Delcourt, Cécile
