Macrophage-Hosted Porphyromonas gingivalis Is a Risk Factor for Cataract Development.

PURPOSE: We studied the regulatory association of Porphyromonas gingivalis (PG) and cataracts.

METHODS

PCR and FISH assays were used for detecting PG 16s ribosomal RNA genome, Immunofluorescence was for expression of RpgA in anterior capsular epithelium and fibrosis markers in anterior subcapsular cataract (ASC) model. Flow cytometry was for reactive oxygen species and apoptosis. RNA deep sequencing is for differential gene expression analysis.

RESULTS

PG's 16s ribosomal RNA gene is positively in 43.3% (101/233 cases) of aqueous humor (AH) samples of patients with cataracts, which differs from 4.7% (6/127) of PG-positive AH in patients with glaucoma. Diabetic and high myopia cataracts increase PG-positive AH compared with age-related cataracts. No PG is observed in AH of congenital cataracts. PG is positive in 82% to 94% of the cataractous anterior capsule tissues from high myopia and age-related, congenital, and diabetic cataracts. The PG-positive cells in the cataractous anterior capsular epithelium are CD68+/CD14+ macrophages, but not anterior epithelial cells. In rat ASC models, PG injected via the tail vein or PG-carried bone marrow monocytes can migrate into the equatorial lens epithelium in form of PG-positive macrophages, which promote ASC progression with upregulation of collagen, fibronectin and α smooth muscle actin (α-SMA) expression, and increase 8-OHdG levels and α-SMA expression in the surrounding lens epithelial cells. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis of the RNA sequencing dataset of ASC tissues shows that signaling pathways related to epithelial-mesenchymal transition, oxidative stress, and cell death are up-regulated in PG + ASC compared with that in ASC alone. Co-culture of supernatants of Raw264.7/PG+ cells with rat primary lens epithelial cells increases the 8-OHdG levels, mitochondrial fission, apoptosis, and expression of α-SMA.

CONCLUSIONS

Chronic infection with PG can access the lens epithelium via macrophages during stress conditions, which promotes cataract development by possibly elevating oxidative stress, apoptosis, and epithelial-mesenchymal transition in lens tissues. PG infection is a novel a risk factor for cataract development.