Abstract
Purpose :
Age-related macular degeneration (AMD) is a disease that arises from complex factors, including diet and inflammation closely linked to the gut microbiome. We examine whether microbiome therapy could modulate the progression of both dry and wet AMD in murine models.
Methods :
For the laser-induced choroidal neovascularization (CNV) model, 7 probiotic strains (Bifidobacterium breve, B. longum subsp. longum, B. longum subsp. infantum, Lactobacillus acidophilus, L. gasseri, Lactococcus lactis, Lacticaseibacillus casei), 3 candidate strains, (Akkermansia muciniphila, Fusobacterium mortiferum, Microbacterium ginsengsoli) and PBS (control group) were administered via gavage to groups of 5 mice per strain, totaling 55 mice. Each strain received 1x109 CFU/200μL microbiome three times a week starting at the age of 6 weeks, and a 60% high-fat diet was introduced from the age of 7 weeks. At 11 weeks of age, laser-induced CNV was induced, followed by OCT and fundus imaging two weeks later. We extracted the RPE-choroid layer in each mouse, and measured the CNV area labeling CD31 antibody using confocal microscopy. To model dry AMD, 52-week-old mice were utilized. The control group and the microbiome treatment groups (five strains, 5 mice per strain) received gavage of PBS or microbiome (1x109 CFU/200μL) three times a week for a total of 16 weeks. Starting from the fourth week of microbial treatment, a 60% high-fat diet was implemented. The extent of drusen deposition and the thickness of the retina-choroid were analyzed.
Results :
Compared to the control group, administering Lactococcus lactis, Akkermansia muciniphila, and Fusobacterium mortiferum significantly reduced CNV area (unpaired t test, P<0.05). Although not statistically significant, B. longum subsp. longum and Lacticaseibacillus casei groups exhibited a trend towards CNV area reduction. In the aged mouse model of dry AMD, a pronounced increase in drusen deposition was observed in the groups treated with Microbacterium ginsengsoli and Fusobacterium mortiferum while significantly lower levels of drusen deposition were observed in the other microbial strains.
Conclusions :
Through the administration of various microbial strains, we explored the potential inhibition of both dry and wet AMD. Further research is needed to investigate the therapeutic implications of these findings.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.