Cui Xuexue, Yi Caijiao, Liu Jian, Qi Jinyan, Deng Wen, Yuan Xiangling, Zhou Ruiqi, Chen Mei, Xiang Qiang, Xu Heping
Aier Academy of Ophthalmology, Central South University, Changsha, Hunan, China.
Aier Eye Institute, Changsha Aier Eye Hospital, Changsha, Hunan, China.
Invest Ophthalmol Vis Sci. 2025 Jul 1;66(9):6. doi: 10.1167/iovs.66.9.6.
The purpose of this study was to understand how the gut microbial system responds to retinal injury.
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.
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).
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.
本研究旨在了解肠道微生物系统对视网膜损伤的反应。
对成年C57BL/6J小鼠进行视网膜激光灼伤或低眼压诱导的视网膜脱离（RD）。1小时、4小时和24小时后，使用伊文思蓝试验评估肠道通透性（8只雄性小鼠和8只雌性小鼠），并通过免疫荧光检查肠道上皮细胞中ZO-1的表达。通过流式细胞术评估循环免疫细胞。在严格无菌条件下收集对照小鼠和激光照射小鼠（n = 8）的粪便，并使用Illumina平台进行16S DNA双端测序。在用佩罗斯抗生素治疗后（n = 8），评估肠道菌群失调对视网膜伤口愈合的影响。通过免疫组织化学检查视网膜病变。
视网膜激光损伤在1小时内显著改变了肠道微生物谱（β多样性，多反应置换程序[MRPP]，P = 0.05）。与未激光照射的对照组相比，Lignipirellula和Faecalibacterium的丰度分别降低了100倍和6.67倍，而Akkermansia和Colidextribacter的丰度分别升高了3.65倍和17.72倍。视网膜激光灼伤和RD而非假手术，在1小时和4小时时分别使肠道通透性增加了3.82倍和24.76倍，破坏了肠道上皮ZO-1的表达，并在1小时和4小时时伴随着循环中性粒细胞和单核细胞数量的增加（P < 0.01）。抗生素治疗减轻了激光/RD诱导的肠道通透性以及中性粒细胞和单核细胞数量的增加（在RD中，P < 0.05）。抗生素治疗还显著降低了激光诱导的脉络膜新生血管形成（CNV；P < 0.001）和RD介导的光感受器凋亡的严重程度（P < 0.01），并抑制了Gr-1+中性粒细胞（CNV，P < 0.001）和Iba-1+细胞浸润（P < 0.001）。
存在视网膜-肠道轴。视网膜损伤诱导肠道微生物快速改变，进而调节先天性免疫细胞激活并调节伤口愈合反应。
