Abstract
Purpose :
The gut microbiome is associated with various aspects of health and disease, particularly in abnormalities associated with inflammatory processes in degenerative diseases. We speculate that imbalance in the gut microbiome can cause dysregulation of inflammatory responses in the retina. This study was undertaken to ascertain how the gut microbiome might initiate an inflammatory response in the ocular environment, leading to retinal degenerative changes.
Methods :
8-month-old Cryba1-floxed mice were fed either normal chow or high-fat, cholesterol enriched chow (HFC) for 4 months. Fecal samples were collected and 16S rRNA sequencing was performed to access changes in the gut microbiome. Changes in the immune cell population in the peripheral blood were evaluated by flow cytometry. Retinal pigment epithelium (RPE) morphology and immune cell (microglia, neutrophils) localization in the retina were evaluated by immunohistochemistry with ZO-1 and Iba1/Ly6G staining, respectively.
Results :
We found that 12-month-old Cryba1-floxed mice fed with HFC for 4 months showed a much higher number of clostridia in fecal samples, compared to age-matched normal chow fed floxed mice. At the same age, flow cytometry analysis showed marked upregulation in the number and activation status of both neutrophils and monocytes in the peripheral blood, compared to normal chow fed floxed mice. Such peripheral immune cell activation was not observed in normal chow fed Cryba1 cKO mice, a well characterized animal model of atrophic age-related macular degeneration (AMD). Furthermore, HFC-treatment to Cryba1-floxed mice showed alterations in RPE morphology and immune cell infiltration into the subretinal space.
Conclusions :
Our results suggest that activation of the peripheral immune system might be the possible link between HFC-induced abnormalities in gut microbiome and subsequent inflammatory changes in the ocular environment. Thus, we have developed a novel model to explore the interaction between the overall immune system of the body and the immune cell population specific to the eye during AMD. This research is the first of its kind and could reveal a potential treatment target in the early stages of atrophic AMD, a complex disease with multiple factors, particularly inflammation.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.