Lactobacillus paracasei KW3110 Suppresses Inflammatory Stress-Induced Premature Cellular Senescence of Human Retinal Pigment Epithelium Cells and Reduces Ocular Disorders in Healthy Humans

• Published in: International journal of molecular sciences Vol. 21; no. 14; p. 5091
• Main Authors: Yamazaki, Takahiro, Suzuki, Hiroaki, Yamada, Sayuri, Ohshio, Konomi, Sugamata, Miho, Yamada, Takahiro, Morita, Yuji
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 18.07.2020; MDPI
• Subjects: Adenosine Triphosphate - toxicity; Adult; Animals; Apoptosis; Cell cycle; Cell Cycle Checkpoints - drug effects; Cell Death - drug effects; Cell growth; Cell Line; Cell Proliferation - drug effects; Cellular Senescence - drug effects; Cytokines; Cytokines - metabolism; Escherichia coli; Eye Diseases - drug therapy; Female; Gene expression; Genotype & phenotype; Humans; Immune system; Inflammation - drug therapy; Inflammation - immunology; Interleukin-10 - metabolism; Lactobacillus paracasei; Lipopolysaccharides - toxicity; Macrophages - drug effects; Male; Mice; Middle Aged; Probiotics - therapeutic use; Retina - drug effects; Retina - immunology; Retina - pathology; Retinal Pigment Epithelium - cytology; Retinal Pigment Epithelium - drug effects; Retinal Pigment Epithelium - immunology; Retinal Pigment Epithelium - pathology; Senescence; Tight Junctions - metabolism; Viral infections; cellular senescence; eye fatigue; inflammation; retina; lactic acid bacteria; probiotics
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21145091

Lactobacillus paracasei KW3110 (KW3110) has anti-inflammatory effects and mitigates retinal pigment epithelium (RPE) cell damage caused by blue-light exposure. We investigated whether KW3110 suppresses chronic inflammatory stress-induced RPE cell damage by modulating immune cell activity and whether it improves ocular disorders in healthy humans. First, we showed that KW3110 treatment of mouse macrophages (J774A.1) produced significantly higher levels of interleukin-10 as compared with other lactic acid bacterium strains (all p < 0.01). Transferring supernatant from KW3110- and E. coli 0111:B4 strain and adenosine 5′-triphosphate (LPS/ATP)-stimulated J774A.1 cells to human retinal pigment epithelium (ARPE-19) cells suppressed senescence-associated phenotypes, including proliferation arrest, abnormal appearance, cell cycle arrest, and upregulation of cytokines, and also suppressed expression of tight junction molecule claudin-1. A randomized, double-blind, placebo-controlled parallel-group study of healthy subjects (n = 88; 35 to below 50 years) ingesting placebo or KW3110-containing supplements for 8 weeks showed that changes in critical flicker frequency, an indicator of eye fatigue, from the week-0 value were significantly larger in the KW3110 group at weeks 4 (p = 0.040) and 8 (p = 0.036). These results suggest that KW3110 protects ARPE-19 cells against premature senescence and aberrant expression of tight junction molecules caused by chronic inflammatory stress, and may improve chronic eye disorders including eye fatigue.