Investigating the Enigmatic Link Between Periodontal Inflammation and Retinal Degeneration
Objectives: Many clinical studies link Chronic Periodontitis(CP) to systemic disorders and lately to age-related macular degeneration(AMD), a leading cause of irreversible vision loss in elderly. Porphyromonas gingivalis(Pg), keystone oral-pathobiont, has documented ability to invade epithelial, fibroblasts and dendritic cells. Our study was designed with an objective to interrogate the role of Pg and its fimbriae-mutant infection in human retinal-pigment epithelial(ARPE-19) cells and retro-orbitally injected mice retina, thus revealing unknown molecular link between CP and AMD.
Methods: ARPE-19 cells were infected with Pg and its isogenic mutant strains expressing only minor-Mfa1 fimbriae(DPG3) and major-FimA fimbriae(MFI) with 1-MOI for 24hrs, relative to uninfected control. The genes of interest were analyzed by qPCR. For uptake of Pg, pre-labeled with CFSE, ARPE-19 cells were quantified with confocal imaging. Retinal morphology in Pg injected (retro-orbital) CD1-mice compared with PBS-treated controls, studied with SD-OCT imaging.
Results: A significant uptake of Pg381 by ARPE-19 cells was detected. qPCR shows significant(P<0.05) increase(>4fold) in expression levels of immunosuppression, angiogenesis/neo-vasculogenesis markers- IDO1, VEGF-A, CXCR4 and CXCL12 in Pg infected ARPE-19 cells compared with uninfected control. Complement regulatory molecules related genes- CFH, Vitronectin, CLU were upregulated, whereas CFI downregulated. The retinal and choroidal thickness considerably reduced in Pg strains injected mice retina compared to controls, consistent with retinal degenerative phenotype. Interestingly, numerous fibrovascular proliferations, new fragile micro blood vessels with blood/fluid leakage in both big and small choroidal vessels observed in Pg injected retinae compared to control group.
Conclusions: This is the first study to demonstrate the role of chronic periodontal inflammation induced by Pg-strains in AMD pathogenesis. We conclude that invasion of RPE by Pg & mutants elevate AMD-related genes involved in angiogenesis; immunosuppression and complement activation which might be the target molecules for both diseases. Successive studies would distinguish specific causal role of Pg in AMD pathogenesis.