Abstract
Presentation Description :
Endogenous bacterial endophthalmitis (EBE) is an intraocular infection resulting from the hematogenous migration of bacteria from a distant infection site to the eye, breach of the blood-retinal barrier (BRB), and invasion of the vitreous. The often poor visual outcome and potential for bilateral blindness make EBE one of the most destructive and devastating ocular infections. Diabetes is the leading predisposing condition for EBE, and is present in approximately one-third of cases involving an underlying condition. The leading bacterial etiological agents of EBE are Klebsiella pneumoniae and Staphylococcus aureus. Currently, the specific bacterial factors that contribute to the migration of K. pneumoniae and S. aureus into the eye and the establishment of EBE have not been identified. In order to elucidate the mechanisms of EBE pathogenesis, we developed a murine model of diabetes-associated EBE and made the key observation of a correlation between diabetes development and the incidence of both K. pneumoniae and S. aureus EBE. However, while K. pneumoniae was unable to cause EBE in nondiabetic mouse eyes, S. aureus was able to cross the BRB and initiate EBE in the absence of diabetes. Additionally, we demonstrated that alterations in the retinal pigment epithelium (RPE) component of the outer BRB also correlated with S. aureus EBE incidence, but these alterations were not required for EBE development. These results suggested that S. aureus produces factors that facilitate BRB breakdown and invasion of the eye. To begin to identify these factors, we compared a strain of S. aureus with an isogenic mutant defective in exotoxin production in an in vitro outer BRB model. We demonstrated that the mutant exhibited a reduced capacity to alter RPE tight junctions and traverse an intact RPE barrier relative to the wildtype strain. Among the exotoxins produced by S. aureus, α-toxin has been demonstrated to contribute to experimental direct injection endophthalmitis in rabbits but its role in EBE is unknown. Using our EBE mouse model, we observed that wildtype S. aureus resulted in a higher incidence of EBE and higher intraocular bacterial concentrations relative to an isogenic mutant deficient in α-toxin production. This suggested that α-toxin contributes to EBE development. Studies are ongoing to elucidate the mechanisms by which α-toxin contributes to EBE, possibly through the disruption of the BRB.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.