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Purpose/Aim: Klebsiella pneumoniae causes a blinding infection called endogenous endophthalmitis. The role of innate immune recognition of K. pneumoniae in the eye during infection is not known. We hypothesized that intraocular recognition of K. pneumoniae was mediated by Toll-like receptor (TLR)-4 and may be dependent on MagA-regulated hypermucoviscosity. Materials and Methods: Experimental endophthalmitis was induced in C57BL/6J or TLR4−/− mice by intravitreal injection of 100 CFU of wild type or ΔmagA K. pneumoniae. Infection and inflammation were quantified by determining viable K. pneumoniae per eye, retinal responses via electroretinography, myeloperoxidase activity of infiltrating neutrophils and the proinflammatory cytokine and chemokine response. Results: C57BL/6J and TLR4−/− mice could not control intraocular wild-type K. pneumoniae growth. TLR4−/− mice were less able than C57BL/6J to control the intraocular growth of ΔmagA K. pneumoniae. Retinal function testing suggested that infection with ΔmagA K. pneumoniae resulted in less retinal function loss. There was a TLR4-dependent delay in initial neutrophil recruitment, regardless of the infecting organism. The proinflammatory cytokine/chemokine data supported these results. These findings were not due to an inability of TLR4−/− neutrophils to recognize or kill K. pneumoniae. Conclusions: These studies suggest that TLR4 is important in the early intraocular recognition and host response to K. pneumoniae. However, the role of MagA in TLR4-mediated intraocular recognition and subsequent inflammation is less clear. [ABSTRACT FROM AUTHOR]

B. cereus possesses flagella which allow the organism to migrate within the eye during a blinding form of intraocular infection called endophthalmitis. Because flagella is a ligand for Toll-like receptor 5 (TLR5), we hypothesized that TLR5 contributed to endophthalmitis pathogenesis. Endophthalmitis was induced in C57BL/6J and TLR5−/− mice by injecting 100 CFU of B. cereus into the mid-vitreous. Eyes were analyzed for intraocular bacterial growth, retinal function, and inflammation by published methods. Purified B. cereus flagellin was also injected into the mid-vitreous of wild type C57BL/6J mice and inflammation was analyzed. TLR5 activation by B. cereus flagellin was also analyzed in vitro. B. cereus grew rapidly and at similar rates in infected eyes of C57BL/6J and TLR5−/− mice. A significant loss in retinal function in both groups of mice was observed at 8 and 12 hours postinfection. Retinal architecture disruption and acute inflammation (neutrophil infiltration and proinflammatory cytokine concentrations) increased and were significant at 8 and 12 hours postinfection. Acute inflammation was comparable in TLR5−/− and C57BL/6J mice. Physiological concentrations of purified B. cereus flagellin caused significant inflammation in C57BL/6J mouse eyes, but not to the extent of that observed during active infection. Purified B. cereus flagellin was a weak agonist for TLR5 in vitro. These results demonstrated that the absence of TLR5 did not have a significant effect on the evolution of B. cereus endophthalmitis. This disparity may be due to sequence differences in important TLR5 binding domains in B. cereus flagellin or the lack of flagellin monomers in the eye to activate TLR5 during infection. Taken together, these results suggest a limited role for flagellin/TLR5 interactions in B. cereus endophthalmitis. Based on this and previous data, the importance of flagella in this disease lies in its contribution to the motility of the organism within the eye during infection. [ABSTRACT FROM AUTHOR]

Bacillus endophthalmitis is one of the most devastating intraocular infections, frequently resulting in significant vision loss, if not loss of the eye itself, in only a few days. This review summarizes recent research focused on characterizing the interactions between Bacillus and the host response during endophthalmitis. Analyses of the contribution of Bacillus toxins and cell wall components, and the behavior of the organism during progressive disease are discussed. A better understanding of the host/pathogen interactions occurring during endophthalmitis is critical for the development of novel therapeutic agents designed to impede the progression of infection and protect vision. [ABSTRACT FROM AUTHOR]

Presents comments on research articles published in the periodical 'Archives of Ophthalmology,' as of September 2001. Selective citation of evidence regarding photoreceptor loss in glaucoma; Effects of corticosteroid and antibiotic therapy for bacillus endophthalmitis; Use of porous polyethylene orbital implants; Benchmarks for ranking and improving ophthalmology residency programs.

Purpose: Bacillus causes a sight-threating infection of the posterior segment of the eye. The robust intraocular inflammatory response in this disease is likely activated via host innate receptor interactions with components of the Bacillus cell envelope. S-layer proteins (SLPs) of some Gram-positive pathogens contribute to the pathogenesis of certain infections. The potential contributions of SLPs in eye infection pathogenesis have not been considered. Here, we explored the role of a Bacillus SLP (SlpA) in endophthalmitis pathogenesis., Methods: The phenotypes and infectivity of wild-type (WT) and S-layer deficient (ΔslpA) Bacillus thuringiensis were compared. Experimental endophthalmitis was induced in C57BL/6J mice by intravitreally injecting 100-CFU WT or ΔslpA B. thuringiensis. Infected eyes were analyzed by bacterial counts, retinal function analysis, histology, and inflammatory cell influx. SLP-induced inflammation was also analyzed in vitro. Muller cells (MIO-M1) were treated with purified SLP. Nuclear factor-κB (NF-κB) DNA binding was measured by ELISA and expression of proinflammatory mediators from Muller cells was measured by RT-qPCR., Results: Tested phenotypes of WT and ΔslpA B. thuringiensis were similar, with the exception of absence of the S-layer in the ΔslpA mutant. Intraocular growth of WT and ΔslpA B. thuringiensis was also similar. However, eyes infected with the ΔslpA mutant had significantly reduced inflammatory cell influx, less inflammatory damage to the eyes, and significant retention of retinal function compared with WT-infected eyes. SLP was also a potent stimulator of the NF-κB pathway and induced the expression of proinflammatory mediators (IL6, TNFα, CCL2, and CXCL-1) in human retinal Muller cells., Conclusions: Taken together, our results suggest that SlpA contributes to the pathogenesis of Bacillus endophthalmitis, potentially by triggering innate inflammatory pathways in the retina.

Purpose: To test the hypothesis that blood-retinal barrier compromise is associated with the development of endogenous Staphylococcus aureus endophthalmitis., Methods: To compromise the blood-retinal barrier in vivo, streptozotocin-induced diabetes was induced in C57BL/6J mice for 1, 3, or 5 months. Diabetic and age-matched nondiabetic mice were intravenously injected with 108 colony-forming units (cfu) of S. aureus, a common cause of endogenous endophthalmitis in diabetics. After 4 days post infection, electroretinography, histology, and bacterial counts were performed. Staphylococcus aureus-induced alterations in in vitro retinal pigment epithelial (RPE) cell barrier structure and function were assessed by anti-ZO-1 immunohistochemistry, FITC-dextran conjugate diffusion, and bacterial transmigration assays., Results: We observed one bilateral infection in a control, nondiabetic animal (mean = 1.54 × 103 ± 1.78 × 10² cfu/eye, 7% incidence). Among the 1-month diabetic mice, we observed culture-confirmed unilateral infections in two animals (mean = 5.54 × 10² ± 7.09 × 10² cfu/eye, 12% incidence). Among the 3-month diabetic mice, infections were observed in 11 animals, three with bilateral infections (mean = 2.67 × 10² ± 2.49 × 10² cfu/eye, 58% incidence). Among the 5-month diabetic mice, we observed infections in five animals (mean = 7.88 × 10² ± 1.08 × 10³ cfu/eye, 33% incidence). In vitro, S. aureus infection reduced ZO-1 immunostaining and disrupted the barrier function of cultured RPE cells, resulting in diffusion of fluorophore-conjugated dextrans and transmigration of live bacteria across a permeabilized RPE barrier., Conclusions: Taken together, these results indicated that S. aureus is capable of inducing blood-retinal barrier permeability and causing endogenous bacterial endophthalmitis in normal and diabetic animals.

Purpose: Endogenous endophthalmitis secondary to Klebsiella pneumoniae liver abscess is a blinding infection that is being reported more frequently in the literature. The K1 capsule and magA contribute to virulence of systemic infection in mice; however, little is known about the role of magA in secondary ocular infections., Methods: To assess the role of K. pneumoniae capsule in endophthalmitis, the authors induced experimental endophthalmitis by direct inoculation of 100 colony-forming unit wild-type, magA-deficient, or magA-complemented K. pneumoniae into the posterior segments of mouse eyes. Eyes were analyzed by quantitation of viable bacteria, retinal function, and inflammatory cell influx as well as by histology., Results: Wild-type K1 K. pneumoniae caused significant ocular disease. At the end point of 24 hours postinfection, eyes infected with wild-type K. pneumoniae retained significantly less retinal A-wave function than eyes infected with an isogenic magA-mutant strain. B-wave function retention was also greater in eyes infected with the magA mutant than with wild-type K. pneumoniae. Additionally, intraocular growth of the magA-deficient strain was less than it was in the wild-type strain. The amount of myeloperoxidase elicited was also significantly higher for wild-type-infected eyes at 24 hours., Conclusions: These results indicate that in the eye, the K1 capsule of invasive K. pneumoniae significantly contributes to the ability of the bacteria to disrupt retinal function, to grow to high density, and to persist despite immune cell recruitment.