AUTHOR=Huang Shengyuan , Cao Guoqin , Dai Dong , Xu Qiuping , Ruiz Sunniva , Shindo Satoru , Nakamura Shin , Kawai Toshihisa , Lin Jiang , Han Xiaozhe 

TITLE=Porphyromonas gingivalis outer membrane vesicles exacerbate retinal microvascular endothelial cell dysfunction in diabetic retinopathy

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1167160

DOI=10.3389/fmicb.2023.1167160

ISSN=1664-302X

ABSTRACT=<p>Diabetic retinopathy (DR) is one of the leading causes of blindness. Periodontitis is one of the highest oral incidences and has been closely related to various systemic conditions through <italic>Porphyromonas gingivalis</italic> (<italic>P. gingivalis</italic>). <italic>P. gingivalis</italic> OMVs, derived from <italic>P. gingivalis</italic>, can cause endothelial dysfunction and potentially affect microvascular diseases. Current epidemiological studies provide limited evidence suggesting that periodontitis is associated with DR. However, there is a lack of basic research elucidating how periodontitis affects the severity of DR. This study aimed to explore the potential of <italic>P. gingivalis</italic> OMVs to contribute to the pathogenesis of DR and explore how it affect the retinal microvascular endothelium. The results demonstrated that <italic>P. gingivalis</italic> OMVs accelerated the blood-retinal barrier damage in DR mice. <italic>In vitro</italic> studies showed that the expression of inflammatory factors in human retinal microvascular endothelial cells (HRMECs) was increased after <italic>P. gingivalis</italic> OMVs stimulation, and the increased reactive oxygen species production,  mitochondrial dysfunction, apoptosis, and altered endothelial permeability were observed in HRMECs under <italic>P. gingivalis</italic> OMVs stimulation. In addition, we found that protease-activated receptor-2 (PAR-2) regulated OMVs-induced TNF-α, MMP-9 mRNA expression, cell death, and endothelial permeability. Overall, we suggested that <italic>P. gingivalis</italic> OMVs induced mitochondria-related cell death of HRMECs and accelerated endothelial dysfunction, thus aggravating DR, in which PAR-2 plays a potential role. This study is the first research report to delineate the potential molecular mechanism of <italic>P. gingivalis</italic> OMVs on DR pathogenesis, which uniquely focused on elucidating the possible impact of periodontal pathogen derivatives on DR progression.</p>