肠-视网膜轴机制及其与眼科疾病的相互作用

Interaction mechanism between gut-retina axis and eye diseases

肠道菌群是维持机体稳态的重要组成部分,近年来,随着16S rRNA和宏基因组等测序技术的快速发展,人们对微生物有了更加深入而全面的认识,在动物和人类中的研究证实肠道菌群不仅参与免疫性、代谢性和神经系统等全身性疾病的病变过程,还与眼病的发生密切相关。宿主高血糖、免疫异常、衰老和高眼压等因素可引起肠道菌群失调,肠-血屏障通透性增加。肠道菌群相关的脂多糖和肽聚糖等病原相关分子模式穿过受损的肠道屏障进入体循环,最终沉积到视网膜和葡萄膜组织中,参与免疫及炎症反应过程,而肠道来源的宿主免疫细胞或损伤相关的分子模式又可加重眼部炎症的级联反应。同时,包括饮食和环境诱导在内的肠道菌群代谢产物,如胆红素、胆汁酸和短链脂肪酸等,通过调节免疫T细胞平衡、miRNA表达和视网膜细胞炎性活化等参与视网膜疾病的进展。本文拟对近年来国内外关于肠道菌群与糖尿病视网膜病变、葡萄膜炎、年龄相关性黄斑变性和青光眼的相关研究进行综述,探讨肠道菌群通过肠-视网膜轴参与眼科疾病的可能机制,为眼部疾病的机理研究和防治提供一些新的思路。

Gut microbiome is an important part of maintaining human homeostasis.In recent years,with the rapid development of sequencing technologies such as 16S rRNA and metagenome,people have a deeper and more comprehensive understanding about microorganisms.Studies in animals and humans have confirmed that the gut microbiome is not only involved in the pathological process of systemic diseases such as immune,metabolic and neurological disorders,but is also closely related to eye diseases.Factors such as host high blood glucose,immune disorders,aging,high intraocular pressure can cause gut microbiota dysbiosis and increase gut-blood barrier permeability.Lipopolysaccharide,peptidoglycan and other pathogen-associated molecular patterns enter the systemic circulation through the damaged gut barrier and eventually reach the retina and uveitis where they participate the immune and inflammatory response process.In addition,gut-derived host immune cells or injury-related molecular patterns may exacerbate the ocular inflammatory cascade.At the same time,metabolites of microbiota,including those induced by diet and environment factors,such as bilirubin,bile acids and short-chain fatty acids,are involved in the progression of retinal diseases via regulating immune T cell balance,miRNA expression and retinal cell inflammatory activation.This article aims to review the domestic and foreign studies on gut microbiome in diabetic retinopathy,uveitis,age-related macular degeneration and glaucoma in recent years,and discuss the possible mechanisms of gut microbiome in eye diseases via the gut-retina axis in order to provide some new ideas for further study and treatment of eye diseases.