The Gut Microbial System Responds to Retinal Injury and Modulates the Outcomes by Regulating Innate Immune Activation.

Abstract

Purpose: The purpose of this study was to understand how the gut microbial system responds to retinal injury.

Methods: Adult C57BL/6J mice were subjected to retinal laser burns or hypotony-induced retinal detachment (RD). One, 4, and 24 hours later, gut permeability (8 male mice and 8 female mice) was assessed using Evan's blue assay and the expression of ZO-1 in intestinal epithelial cells was examined by immunofluorescence. Circulating immune cells were evaluated by flow cytometry. The feces from control and lasered mice (n = 8) were collected under strict sterile conditions and processed for 16S DNA paired-end sequencing using the Illumina platform. The impact of gut dysbiosis on retinal wound healing was evaluated following treatment with Peros antibiotics (n = 8). Retinal pathologies were examined by immunohistochemistry.

Results: Retinal laser injury significantly altered gut microbial profiles within 1 hour (β-diversity, multi-response permutation procedure [MRPP], P = 0.05). The abundance of Lignipirellula and Faecalibacterium was 100- and 6.67-fold lower, and the abundance of Akkermansia and Colidextribacter was 3.65- and 17.72-fold higher than non-lasered controls, respectively. Retinal laser burns and RD, not sham surgery, increased gut permeability at 1 hour and 4 hours by 3.82- and 24.76-fold, respectively, disrupted intestinal epithelial ZO-1 expression, accompanied by an increased population of circulating neutrophils and monocytes (P < 0.01) at 1 hour and 4 hours. Antibiotic treatment attenuated laser-/RD-induced gut permeability and the increased neutrophils and monocytes (in RD, P < 0.05). Antibiotic treatment also significantly reduced the severity of laser-induced choroidal neovascularization (CNV; P < 0.001) and RD-mediated photoreceptor apoptosis (P < 0.01), and suppressed Gr-1+ neutrophils (CNV, P < 0.001) and Iba-1+ cell infiltration (P < 0.001).

Conclusions: A retina-gut axis exists. Retinal injury induces rapid gut microbial alteration, which in turn modulates innate immune cell activation and regulates the wound healing response.