Abstract

Age-related macular degeneration (AMD) is a chronic degenerative disease of the retina. Recent reports have highlighted the potential role of mucosal surface microbes in the pathogenesis of AMD. In this case-control study, the composition of the nasal and oral microbiota in newly diagnosed neovascular age-related macular degeneration cases (6 male, 7 female) was compared to controls without retinal diseases (2 male, 3 female). PCR amplification of 16S rRNA genes was performed with universal primers amplifying the V4 variable region (515F-806R). Distinct microbial community characterization was achieved using Principal Coordinates Analysis (PCoA) of the Bray-Curtis index with comparative analysis between cases and controls performed within QIIME 2. Sequencing of all cases and controls revealed clear separation with strong beta diversity between oral and nasal microbial communities (p < 0.001). Microbial composition differed between cases and controls in both oral and nasal samples. The top three oral microbes identified as different compared to controls included Burkholderiales (7.41 log2fold change, p = 3.29E-05), Actinomyceataceae (6.22 log2fold change, p = 3.73E-06) and Gemella (5.28 log2fold change, p = 0.0002). The top three nasal microbes identified as different compared to controls included Rothia (13.6 log2fold change, p = 3.63E-18), Actinobacteria (10.29 log2fold change, p = 9.81E-10) and Propionibacteriales (8.73 log2fold change, p = 6.74E-09). These relative shifts in communities of bacteria detected in newly diagnosed neovascular AMD patients may suggest additional mechanistic links in disease pathogenesis.

Highlights

  • Age-related macular degeneration (AMD) is a chronic degenerative disease of the retina

  • The aberrant immune response in AMD patients is at least partially genetically mediated by polymorphisms at two genetic loci, complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2), both of which have been strongly implicated in disease initiation and progression[5,6,7]

  • In order to determine whether oral and nasal microbiota were associated with newly developed neovascular AMD, 16S rRNA sequences were compared between 13 treatment naïve, newly diagnosed cases of neovascular AMD and 5 controls without of any evidence of retinal disease

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Summary

Introduction

Age-related macular degeneration (AMD) is a chronic degenerative disease of the retina. Recent reports have highlighted the potential role of mucosal surface microbes in the pathogenesis of AMD In this case-control study, the composition of the nasal and oral microbiota in newly diagnosed neovascular age-related macular degeneration cases (6 male, 7 female) was compared to controls without retinal diseases (2 male, 3 female). The top three nasal microbes identified as different compared to controls included Rothia (13.6 log2fold change, p = 3.63E-18), Actinobacteria (10.29 log2fold change, p = 9.81E10) and Propionibacteriales (8.73 log2fold change, p = 6.74E-09) These relative shifts in communities of bacteria detected in newly diagnosed neovascular AMD patients may suggest additional mechanistic links in disease pathogenesis. Microbes have been implicated in the induction of local inflammation, leading to increased mucosal permeability, thereby allowing inflammogenic material direct access to the systemic circulation This material up-regulates immune mediators at distal sites, inducing local inflammatory pathways in end organs. The diverse microbial environment surrounding the eye, namely the nose and mouth, represents a unique region where microbial diversity could lead to distant chronic inflammatory changes in the eye

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