Abstract
Purpose :
Coagulase-negative staphylococci (CONS), including Staphylococcus (S) epidermidis are responsible for 70% of all exogenous bacterial endophthalmitis. However, the pathogenesis of CONS endophthalmitis is limited epidemiologically and in clinical case reports; in part, this could be due to lack of suitable experimental models. Here, we developed a mouse model of S. epidermidis endophthalmitis and evaluated retinal innate immune responses. In vitro studies were also performed using cultured retinal and myeloid cells.
Methods :
Endophthalmitis was induced by intravitreal injections of S. epidermidis and both dose-dependent and time-course studies were performed. Disease progression was monitored by an eye exam using slit-lamp microscopy and ERG analyses. Eyes were enucleated for enumeration of bacterial burden and assessment of inflammatory mediators using RT-PCR and ELISA assays. For in vitro studies, muller glial cells, retinal pigment epithelium and mouse bone marrow-derived macrophages (BMDM) were challenged with S. epidermidis and the expression levels of pro-inflammatory cytokines and chemokines were deduced at various time points post infection. The induction of inflammatory signaling was assessed by western blot.
Results :
Our data showed that S. epidermidis was rapidly cleared from mice eyes and a relatively higher dose was needed to cause endophthalmitis. A time-course study revealed that bacterial load peaked at 24h post-infection followed by a gradual decline up to 72h. The production of inflammatory mediators followed a similar trend with reduced levels as bacterial burden decreased. In vitro studies showed differential expression of inflammatory mediators, with BMDM cells showing increased levels as compared to RPE and Muller glia. Western blot analyses revealed the induction of NF-kB and other MAPK (ERK and p38) signaling in S. epidermidis infected mice eyes and cultured cells.
Conclusions :
S. epidermidis evoked innate immune responses in both mouse eyes and cultured cells. However, it did not cause severe endophthalmitis even when injected at a higher dose, indicating robust retinal innate immunity to efficiently clear CONS.
This is a 2021 ARVO Annual Meeting abstract.