The Study Of Human Microecology In Relation To Diabetic Dry Eye And Diabetic Retinopathy

Objective: To explore the relationship between human microecology and diabetesrelated eye diseases: 1.to explore the relationship between human ocular surface microbiota and diabetes-related dry eye;and 2.to explore the relationship between human gut microbiota and diabetic retinopathy.Methods: In the first part,the study of ocular surface microbiota and diabetesrelated dry eye,four groups were included in this study: diabetic dry eye group,nondiabetic dry eye group,diabetic non-dry eye group and non-diabetic non-dry eye group.Tears secreted under natural conditions were collected by tear paper for DNA extraction,and 16 s ribosomal RNA(16S rRNA)sequencing technology was used to detect tear microorganisms in the four groups and to statistically analyze the specificity of tear microorganisms on the ocular surface of the four groups and the uniqueness of ocular surface microorganisms in diabetic dry eyes.In the second part,gut microbiota and diabetic retinopathy,two groups were included: those who had been diagnosed with diabetes for more than 15 years and had no diabetic retinopathy at four consecutive years of community screening,and those who had been diagnosed with diabetes for less than five years but had diabetic retinopathy at four years of community screening.By collecting stool and serum from these two populations,The structure of the microbial community in stool and the concentration of short-chain fatty acids in serum were analyzed using 16 S rRNA sequencing and gas chromatography(GC-MS)techniques;secondly,in cellular and animal experiments,the primary human retinal endothelial cells and streptozotocin-induced diabetic mouse models were intervened through differential substance propionate screened in the population samples;finally,long-term dietary studies were conducted on a further extended target population by distributing semiquantitative food frequency questionnaires(FFQ),and a dietary study was conducted to calculate the intake of essential nutrients by comparing the Chinese food composition table and conducting statistical analysis.Results: In the first part,this study found that the tear microbial communities of the four groups differed significantly in the following ways: 1.at the five taxonomic levels of Phylum,Class,Order,Family,and Genus,the microorganisms of the ocular surface tears of the diabetic dry eye group had the highest abundance of operational taxonomic units(OTUs)among the four groups;2.the microorganisms of the ocular surface tears of the diabetic dry eye population had the highest alpha-and beta-diversity in terms of microbial species diversity;3.the four major microbial phyla at the Phylum level:Proteobacteria,Firmicutes,Actinobacteria,and Bacteroidetes differed among the four groups,especially the abundance of Bacteroidetes in the diabetic dry eye group was significantly higher than the other three groups;4.the core components of tear microorganisms likewise differed among the four groups at the genus level;5.two core microbial members: Unclassified＿Clostridiale and Lactobacillus,were unique to diabetic dry eye patients compared to the other three groups.In the second part,the analysis of population stool samples revealed that: 1.Lactobacillus and Bifidobacterium were more abundant in the 15-year DR-free group.2.serum propionate were lower in the 15-year DR-free group.3.propionic acid inhibited the proliferation of primary human retinal microvascular endothelial cells(HRMECs)in vitro experiments and promote the expression of the inflammatory factor IL-6 in vitro and vivo experiments.4.the semiquantitative food frequency questionnaire(FFQ)of the population from the community study found that the population in the 15-year DR-free group was biased to consume lower carbohydrates and higher fat.Conclusions: In this study,we found that the ocular surface tear microbial community in the diabetic dry eye population is unique,higher microbial abundance and more complex diversity and specific dominant genera.New treatment options are needed for this group of dry eyes.Secondly,in some people with long duration diabetes and consistently free of DR,high abundance of probiotics in the gut,low blood propionate concentrations,higher fat and lower carbohydrate intake in the daily diet are associated.Propionate,one of the SCFAs,may be involved in damaging the retinal vascular endothelium and has a contributory role in the development of DR.