Association of Lipopolysaccharide-Type Endotoxins with Retinal Neurodegeneration: The Alienor Study

Abstract

PurposeLipopolysaccharide (LPS) -type endotoxins are naturally found in the gut microbiota and there is emerging evidence linking gut microbiota and neuroinflammation leading to retinal neurodegeneration. Thinning of the retinal nerve fiber layer (RNFL) is a biomarker of retinal neurodegeneration, and a hallmark of glaucoma, the second leading cause of blindness worldwide. We assessed the association of a blood biomarker of LPS with peripapillary RNFL thickness (RNFLT) and its longitudinal evolution up to 11 years. DesignThe Alienor study is a single center prospective population-based cohort study. SubjectsThe studied sample of this study includes 1062 eyes of 548 participants receiving at least one gradable RNFL measurement. MethodsPlasma esterified 3-hydroxy fatty acids (3-OH FAs) were measured as a proxy of LPS burden. RNFLT was acquired using spectral domain optical coherence tomography imaging every two years from 2009 to 2020 (up to 5 visits). Main Outcome MeasureAssociations of plasma esterified 3-OH FAs with RNFLT were assessed using linear mixed models. ResultsMean age of the included 548 participants was 82.4 ± 4.3 years and 62.6 % were women. Higher plasma esterified 3-OH FAs was significantly associated with thinner RNFLT at baseline (Coefficient Beta (ß)= -1.42 microns for 1 SD-increase in 3-OH FAs, 95% confidence interval [-2.56; -0.28], p = 0.02). This association remained stable after multivariate adjustment for potential confounders. No statistically significant association was found between 3-OH FAs and longitudinal RNFLT change. ConclusionsHigher plasma esterified 3-OH FAs were associated with thinner RNFLT at baseline, indicating an involvement of LPS in the early processes of optic nerve neurodegeneration and highlighting the potential importance of the human microbiota in preserving retinal health.