Housing RCS rats under specific pathogen-free conditions mildly ameliorates retinal degeneration and alters intestine microbiota

Abstract

Abstract Retinitis pigmentosa (RP) is a genetic blinding disease with over 80 causative genes. Disease progression varies between patients with similar genetic backgrounds. We assessed the association between environment, gut microbiota, and retinal degeneration in the RP rat model Royal College of Surgeons (RCS). The rats were born and raised for two generations under specific pathogen-free (SPF, n = 69) or non-SPF conditions (n = 48). At the age of four weeks, SPF rats had significantly shorter dark-adapted a-wave and dark and light-adapted b-wave implicit times by electroretinogram (p = 0.014, p = 9.5*10−6, p = 0.009, respectively). The SPF rats had significantly less photoreceptor apoptosis at ages four, eight, and twelve weeks (all p < 0.022), significantly thicker debris zone at age 14 weeks, and smaller hypofluorescent lesions in SPF rats at ages 10–16 weeks, especially in the inferior retina. The non-SPF rats had significantly higher microbiota alpha diversity (p = 0.037) and failed to present the age-related maturation of Proteobacteria, Spirochaetes, Actinobacteria, and Bacteroidetes seen in SPF conditions. Specific microbial amplicon sequence variants were reduced in rats with more severe retinal degeneration. Our data suggest an environmental effect on retinal deterioration in RCS rats. These findings may lead to the development of novel microbiome-related interventions for retinal degeneration.

Keywords

• Retinitis pigmentosa
• Microbiome
• RCS rats
• Retinal degeneration
• Photoreceptors