Housing RCS rats under SPF conditions alters intestine microbiota and ameliorates retinal degeneration

Abstract

Purpose : To investigate the association between gut microbiome composition and retinal degeneration rate in RCS rats raised in specific pathogen free (SPF) and non-SPF conditions.

Methods : RCS rats were born and raised in Sheba Medical Center animal facility under SPF (n=69) and non-SPF conditions (n=48). Fecal samples were individually collected every two weeks for microbiome analysis and the rats were examined for retinal structure by Spectral Domain Optical Coherence Tomography (SD-OCT), blue light autofluorescence fundus (BL-FAF) imaging and histopathology. Retinal function was assessed by Electroretinogram.

Results : Gut microbiome significantly differed between rats that were raised in non-SPF vs. SPF conditions. 90 different bacterial amplicon sequence variant (ASVs) were increased in non-SPF and other 34 bacterial ASVs were increased in SPF raised rats. Specific bacterial ASVs showed increased abundance with increasing rat age, and those were observed in earlier ages in rats raised in non-SPF conditions compared to rats raised in SPF conditions (p=0.002).
BL-FAF imaging revealed significantly smaller hypofluorescent lesions in rats raised in SPF conditions. This was more specifically noted at the age of 12 weeks, where the hypofluorescent lesion area was 6.8 fold higher non-SPF rats vs. rats raised in SPF conditions (p=0.003). Significantly shorter latencies were recorded for scotopic a- and b-waves and photopic b-waves in rats raised in SPF conditions as early as 4 weeks of age compared to rats raised in non-SPF conditions (p=0.02, p<0.001, p<0.001 respectively). At age of 8 weeks, the scotopic a-wave latency recorded in rats raised in non-SPF conditions was 1.7 fold longer (57.69 ± 11.57 ms) compared to rats raised in SPF conditions (33.11 ± 2.93 ms, p=0.04). SD-OCT total retinal thickness was higher in the superior part of the retina in rats raised in SPF conditions (294.83 ± 12.64 mm) compared with rats raised in non-SPF conditions (260.327 ± 10.76 mm, p=0.05).

Conclusions : Microbial diversity and age-related microbial dynamics were observed in non-SPF vs. SPF rats, in parallel to more rapid and severe retinal degeneration, and may present potential intervention strategy for slowing disease progression.

This is a 2021 ARVO Annual Meeting abstract.