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Roger A Astley
University of Oklahoma Health Sciences Center

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Preprint content
Published: 06 July 2020
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Bacterial endophthalmitis is a devastating infection that can cause blindness following the introduction of organisms into the posterior segment of the eye. Over half of Bacillus endophthalmitis cases result in significant loss of useful vision. Often, these eyes have to be enucleated. Bacillus produces many virulence factors in the eye that may contribute to retinal damage and robust inflammation. This study analyzed Bacillus immune inhibitor A (InhA) metalloproteases, which digest extracellular matrix, tight junction proteins, and antimicrobial proteins. We hypothesized that InhAs contribute to Bacillus intraocular virulence and inflammation. We analyzed phenotypes and infectivity of wild type (WT), InhA1-deficient (ΔinhA1), InhA2-deficient (ΔinhA2), or InhA1, A2, and A3-deficient (ΔinhA1-3) Bacillus thuringiensis. In vitro analysis of growth, proteolysis, and cytotoxicity were compared between B. thuringiensis strains. WT and InhA mutants were similarly cytotoxic to retinal cells. Mutant ΔinhA1 and ΔinhA2 entered log phase growth earlier than WT. Proteolysis of the ΔinhA1-3 mutant was decreased, but this strain grew similar to WT in vitro. Experimental endophthalmitis was initiated by intravitreally infecting C57BL/6J mice with 200 CFU of B. thuringiensis WT or InhA mutants. Intraocular Bacillus and retinal function loss were quantified. Intraocular myeloperoxidase concentrations were quantified and histology was analyzed. Eyes infected with ΔinhA1 or ΔinhA2 strains contained greater numbers of bacteria than eyes infected with WT throughout the course of infection. Eyes infected with single mutants had inflammation and retinal function loss similar to eyes infected with WT strain. Eyes infected with ΔinhA1-3 cleared the infection, with less retinal function loss and inflammation compared to eyes infected with the WT strain. RT-PCR results suggested that single InhA mutant results may be explained by compensatory expression of the other InhAs in these mutants. These results indicate that together, the InhA metalloproteases contribute to the severity of infection and inflammation in Bacillus endophthalmitis.

ACS Style

Erin T Livingston; Huzzatul Mursalin; Phillip S Coburn; Roger Astley; Frederick C Miller; Omar Amayem; Didier Lereclus; Michelle Callegan. Immune Inhibitor A Metalloproteases Contribute to Virulence in Bacillus Endophthalmitis. 2020, 1 .

AMA Style

Erin T Livingston, Huzzatul Mursalin, Phillip S Coburn, Roger Astley, Frederick C Miller, Omar Amayem, Didier Lereclus, Michelle Callegan. Immune Inhibitor A Metalloproteases Contribute to Virulence in Bacillus Endophthalmitis. . 2020; ():1.

Chicago/Turabian Style

Erin T Livingston; Huzzatul Mursalin; Phillip S Coburn; Roger Astley; Frederick C Miller; Omar Amayem; Didier Lereclus; Michelle Callegan. 2020. "Immune Inhibitor A Metalloproteases Contribute to Virulence in Bacillus Endophthalmitis." , no. : 1.

Review
Published: 19 June 2019 in Toxins
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Staphylococcus aureus (S. aureus) is a common pathogen of the eye, capable of infecting external tissues such as the tear duct, conjunctiva, and the cornea, as well the inner and more delicate anterior and posterior chambers. S. aureus produces numerous toxins and enzymes capable of causing profound damage to tissues and organs, as well as modulating the immune response to these infections. Unfortunately, in the context of ocular infections, this can mean blindness for the patient. The role of α-toxin in corneal infection (keratitis) and infection of the interior of the eye (endophthalmitis) has been well established by comparing virulence in animal models and α-toxin-deficient isogenic mutants with their wild-type parental strains. The importance of other toxins, such as β-toxin, γ-toxin, and Panton–Valentine leukocidin (PVL), have been analyzed to a lesser degree and their roles in eye infections are less clear. Other toxins such as the phenol-soluble modulins have yet to be examined in any animal models for their contributions to virulence in eye infections. This review discusses the state of current knowledge of the roles of S. aureus toxins in eye infections and the controversies existing as a result of the use of different infection models. The strengths and limitations of these ocular infection models are discussed, as well as the need for physiological relevance in the study of staphylococcal toxins in these models.

ACS Style

Roger Astley; Frederick C. Miller; Huzzatul Mursalin; Phillip S. Coburn; Michelle C. Callegan. An Eye on Staphylococcus aureus Toxins: Roles in Ocular Damage and Inflammation. Toxins 2019, 11, 356 .

AMA Style

Roger Astley, Frederick C. Miller, Huzzatul Mursalin, Phillip S. Coburn, Michelle C. Callegan. An Eye on Staphylococcus aureus Toxins: Roles in Ocular Damage and Inflammation. Toxins. 2019; 11 (6):356.

Chicago/Turabian Style

Roger Astley; Frederick C. Miller; Huzzatul Mursalin; Phillip S. Coburn; Michelle C. Callegan. 2019. "An Eye on Staphylococcus aureus Toxins: Roles in Ocular Damage and Inflammation." Toxins 11, no. 6: 356.

Journal article
Published: 20 March 2017 in Experimental Eye Research
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Bacterial endophthalmitis is a potentially blinding intraocular infection. The bacterium Bacillus cereus causes a devastating form of this disease which progresses rapidly, resulting in significant inflammation and loss of vision within a few days. The outer surface of B. cereus incites the intraocular inflammatory response, likely through interactions with innate immune receptors such as TLRs. This study analyzed the role of B. cereus pili, adhesion appendages located on the bacterial surface, in experimental endophthalmitis. To test the hypothesis that the presence of pili contributed to intraocular inflammation and virulence, we analyzed the progress of experimental endophthalmitis in mouse eyes infected with wild type B. cereus (ATCC 14579) or its isogenic pilus-deficient mutant (ΔbcpA-srtD-bcpB or ΔPil). One hundred CFU were injected into the mid-vitreous of one eye of each mouse. Infections were analyzed by quantifying intraocular bacilli and retinal function loss, and by histology from 0 to 12 h postinfection. In vitro growth and hemolytic phenotypes of the infecting strains were also compared. There was no difference in hemolytic activity (1:8 titer), motility, or in vitro growth (p > 0.05, every 2 h, 0–18 h) between wild type B. cereus and the ΔPil mutant. However, infected eyes contained greater numbers of wild type B. cereus than ΔPil during the infection course (p ≤ 0.05, 3–12 h). Eyes infected with wild type B. cereus experienced greater losses in retinal function than eyes infected with the ΔPil mutant, but the differences were not always significant. Eyes infected with ΔPil or wild type B. cereus achieved similar degrees of severe inflammation. The results indicated that the intraocular growth of pilus-deficient B. cereus may have been better controlled, leading to a trend of greater retinal function in eyes infected with the pilus-deficient strain. Although this difference was not enough to significantly alter the severity of the inflammatory response, these results suggest a potential role for pili in protecting B. cereus from clearance during the early stages of endophthalmitis, which is a newly described virulence mechanism for this organism and this infection.

ACS Style

Michelle C. Callegan; Salai Madhumathi Parkunan; C. Blake Randall; Phillip S. Coburn; Frederick C. Miller; Austin L. LaGrow; Roger A. Astley; Craig Land; So-Young Oh; Olaf Schneewind. The role of pili in Bacillus cereus intraocular infection. Experimental Eye Research 2017, 159, 69 -76.

AMA Style

Michelle C. Callegan, Salai Madhumathi Parkunan, C. Blake Randall, Phillip S. Coburn, Frederick C. Miller, Austin L. LaGrow, Roger A. Astley, Craig Land, So-Young Oh, Olaf Schneewind. The role of pili in Bacillus cereus intraocular infection. Experimental Eye Research. 2017; 159 ():69-76.

Chicago/Turabian Style

Michelle C. Callegan; Salai Madhumathi Parkunan; C. Blake Randall; Phillip S. Coburn; Frederick C. Miller; Austin L. LaGrow; Roger A. Astley; Craig Land; So-Young Oh; Olaf Schneewind. 2017. "The role of pili in Bacillus cereus intraocular infection." Experimental Eye Research 159, no. : 69-76.

Journal article
Published: 10 June 2016 in Journal of Leukocyte Biology
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During intraocular bacterial infections, the primary innate responders are neutrophils, which may cause bystander damage to the retina or perturb the clarity of the visual axis. We hypothesized that cytokine IL-6 and chemokine CXCL1 contributed to rapid neutrophil recruitment during Bacillus cereus endophthalmitis, a severe form of intraocular infection that is characterized by explosive inflammation and retinal damage that often leads to rapid vision loss. To test this hypothesis, we compared endophthalmitis pathogenesis in C57BL/6J, IL-6-/-, and CXCL1-/- mice. Bacterial growth in eyes of CXCL1-/-, IL-6-/-, and C67BL/6J mice was similar. Retinal function retention was greater in eyes of IL-6-/- and CXCL1-/- mice compared with that of C57BL/6J, despite these eyes having similar bacterial burdens. Neutrophil influx into eyes of CXCL1-/- mice was reduced to a greater degree compared with that of eyes of IL6-/- mice. Histology confirmed significantly less inflammation in eyes of CXCL1-/- mice, but similar degrees of inflammation in IL6-/- and C57BL/6J eyes. Because inflammation was reduced in eyes of infected CXCL1-/- mice, we tested the efficacy of anti-CXCL1 in B. cereus endophthalmitis. Retinal function was retained to a greater degree and there was less overall inflammation in eyes treated with anti-CXCL1, which suggested that anti-CXCL1 may have therapeutic efficacy in limiting inflammation during B. cereus endophthalmitis. Taken together, our results indicate that absence of IL-6 did not affect overall pathogenesis of endophthalmitis. In contrast, absence of CXCL1, in CXCL1-/- mice or after anti-CXCL1 treatment, led to an improved clinical outcome. Our findings suggest a potential benefit in targeting CXCL1 to control inflammation during B. cereus and perhaps other types of intraocular infections.

ACS Style

Salai Madhumathi Parkunan; C. Blake Randall; Roger A. Astley; Glaucia C. Furtado; Sergio A. Lira; Michelle C. Callegan. CXCL1, but not IL-6, significantly impacts intraocular inflammation during infection. Journal of Leukocyte Biology 2016, 100, 1125 -1134.

AMA Style

Salai Madhumathi Parkunan, C. Blake Randall, Roger A. Astley, Glaucia C. Furtado, Sergio A. Lira, Michelle C. Callegan. CXCL1, but not IL-6, significantly impacts intraocular inflammation during infection. Journal of Leukocyte Biology. 2016; 100 (5):1125-1134.

Chicago/Turabian Style

Salai Madhumathi Parkunan; C. Blake Randall; Roger A. Astley; Glaucia C. Furtado; Sergio A. Lira; Michelle C. Callegan. 2016. "CXCL1, but not IL-6, significantly impacts intraocular inflammation during infection." Journal of Leukocyte Biology 100, no. 5: 1125-1134.

Research article
Published: 19 May 2016 in PLOS ONE
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The blood-retinal barrier (BRB) functions to maintain the immune privilege of the eye, which is necessary for normal vision. The outer BRB is formed by tightly-associated retinal pigment epithelial (RPE) cells which limit transport within the retinal environment, maintaining retinal function and viability. Retinal microvascular complications and RPE dysfunction resulting from diabetes and diabetic retinopathy cause permeability changes in the BRB that compromise barrier function. Diabetes is the major predisposing condition underlying endogenous bacterial endophthalmitis (EBE), a blinding intraocular infection resulting from bacterial invasion of the eye from the bloodstream. However, significant numbers of EBE cases occur in non-diabetics. In this work, we hypothesized that dysfunction of the outer BRB may be associated with EBE development. To disrupt the RPE component of the outer BRB in vivo, sodium iodate (NaIO3) was administered to C57BL/6J mice. NaIO3-treated and untreated mice were intravenously injected with 108 colony forming units (cfu) of Staphylococcus aureus or Klebsiella pneumoniae. At 4 and 6 days postinfection, EBE was observed in NaIO3-treated mice after infection with K. pneumoniae and S. aureus, although the incidence was higher following S. aureus infection. Invasion of the eye was observed in control mice following S. aureus infection, but not in control mice following K. pneumoniae infection. Immunohistochemistry and FITC-dextran conjugate transmigration assays of human RPE barriers after infection with an exoprotein-deficient agr/sar mutant of S. aureus suggested that S. aureus exoproteins may be required for the loss of the tight junction protein, ZO-1, and for permeability of this in vitro barrier. Our results support the clinical findings that for both pathogens, complications which result in BRB permeability increase the likelihood of bacterial transmigration from the bloodstream into the eye. For S. aureus, however, BRB permeability is not required for the development of EBE, but toxin production may facilitate EBE pathogenesis.

ACS Style

Phillip S. Coburn; Brandt J. Wiskur; Frederick C. Miller; Austin L. LaGrow; Roger Astley; Michael H. Elliott; Michelle C. Callegan. Bloodstream-To-Eye Infections Are Facilitated by Outer Blood-Retinal Barrier Dysfunction. PLOS ONE 2016, 11, e0154560 -e0154560.

AMA Style

Phillip S. Coburn, Brandt J. Wiskur, Frederick C. Miller, Austin L. LaGrow, Roger Astley, Michael H. Elliott, Michelle C. Callegan. Bloodstream-To-Eye Infections Are Facilitated by Outer Blood-Retinal Barrier Dysfunction. PLOS ONE. 2016; 11 (5):e0154560-e0154560.

Chicago/Turabian Style

Phillip S. Coburn; Brandt J. Wiskur; Frederick C. Miller; Austin L. LaGrow; Roger Astley; Michael H. Elliott; Michelle C. Callegan. 2016. "Bloodstream-To-Eye Infections Are Facilitated by Outer Blood-Retinal Barrier Dysfunction." PLOS ONE 11, no. 5: e0154560-e0154560.

Review article
Published: 03 May 2016 in Progress in Retinal and Eye Research
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Bacterial endophthalmitis is an infection and inflammation of the posterior segment of the eye which can result in significant loss of visual acuity. Even with prompt antibiotic, anti-inflammatory and surgical intervention, vision and even the eye itself may be lost. For the past century, experimental animal models have been used to examine various aspects of the pathogenesis and pathophysiology of bacterial endophthalmitis, to further the development of anti-inflammatory treatment strategies, and to evaluate the pharmacokinetics and efficacies of antibiotics. Experimental models allow independent control of many parameters of infection and facilitate systematic examination of infection outcomes. While no single animal model perfectly reproduces the human pathology of bacterial endophthalmitis, investigators have successfully used these models to understand the infectious process and the host response, and have provided new information regarding therapeutic options for the treatment of bacterial endophthalmitis. This review highlights experimental animal models of endophthalmitis and correlates this information with the clinical setting. The goal is to identify knowledge gaps that may be addressed in future experimental and clinical studies focused on improvements in the therapeutic preservation of vision during and after this disease.

ACS Style

Roger Astley; Phillip S. Coburn; Salai Madhumathi Parkunan; Michelle C. Callegan. Modeling intraocular bacterial infections. Progress in Retinal and Eye Research 2016, 54, 30 -48.

AMA Style

Roger Astley, Phillip S. Coburn, Salai Madhumathi Parkunan, Michelle C. Callegan. Modeling intraocular bacterial infections. Progress in Retinal and Eye Research. 2016; 54 ():30-48.

Chicago/Turabian Style

Roger Astley; Phillip S. Coburn; Salai Madhumathi Parkunan; Michelle C. Callegan. 2016. "Modeling intraocular bacterial infections." Progress in Retinal and Eye Research 54, no. : 30-48.

Case report
Published: 10 February 2016 in American Journal of Ophthalmology Case Reports
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To report a case of polymicrobial keratitis caused by Panotea agglomerans, Escherichia vulneris and coagulase-negative Staphylococcus in a patient who cleaned their extended wear contact lenses with only tap water for 2 weeks. Case report. An adult presented with a painful red eye after wearing the same contact lenses for two weeks. The patient admitted to taking the contacts out in the evening and cleaning them with tap water before reapplying them in the morning. Exam revealed a 2.5 mm paracentral corneal ulcer in the left eye. Culture results from corneal scrapings were positive for P. agglomerans, E. vulneris and coagulase-negative Staphylococcus. This is the first report of P. agglomerans and E. vulneris keratitis in association with contact lens wear. Both strains of P. agglomerans and E. vulneris were pansensitive to all tested antibiotics.

ACS Style

Vincent D. Venincasa; Michelle Callegan; Roger Astley; R. Michael Siatkowski. Contact lens-related polymicrobial keratitis from Pantoea agglomerans and Escherichia vulneris. American Journal of Ophthalmology Case Reports 2016, 1, 5 -7.

AMA Style

Vincent D. Venincasa, Michelle Callegan, Roger Astley, R. Michael Siatkowski. Contact lens-related polymicrobial keratitis from Pantoea agglomerans and Escherichia vulneris. American Journal of Ophthalmology Case Reports. 2016; 1 ():5-7.

Chicago/Turabian Style

Vincent D. Venincasa; Michelle Callegan; Roger Astley; R. Michael Siatkowski. 2016. "Contact lens-related polymicrobial keratitis from Pantoea agglomerans and Escherichia vulneris." American Journal of Ophthalmology Case Reports 1, no. : 5-7.

Immunology and microbiology
Published: 01 November 2015 in Investigative Opthalmology & Visual Science
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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.

ACS Style

Phillip S. Coburn; Brandt J. Wiskur; Roger A. Astley; Michelle C. Callegan. Blood–Retinal Barrier Compromise and EndogenousStaphylococcus aureusEndophthalmitis. Investigative Opthalmology & Visual Science 2015, 56, 7303 -7311.

AMA Style

Phillip S. Coburn, Brandt J. Wiskur, Roger A. Astley, Michelle C. Callegan. Blood–Retinal Barrier Compromise and EndogenousStaphylococcus aureusEndophthalmitis. Investigative Opthalmology & Visual Science. 2015; 56 (12):7303-7311.

Chicago/Turabian Style

Phillip S. Coburn; Brandt J. Wiskur; Roger A. Astley; Michelle C. Callegan. 2015. "Blood–Retinal Barrier Compromise and EndogenousStaphylococcus aureusEndophthalmitis." Investigative Opthalmology & Visual Science 56, no. 12: 7303-7311.

Research article
Published: 24 June 2014 in PLOS ONE
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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.

ACS Style

Salai Madhumathi Parkunan; Roger Astley; Michelle C. Callegan. Role of TLR5 and Flagella in Bacillus Intraocular Infection. PLOS ONE 2014, 9, e100543 .

AMA Style

Salai Madhumathi Parkunan, Roger Astley, Michelle C. Callegan. Role of TLR5 and Flagella in Bacillus Intraocular Infection. PLOS ONE. 2014; 9 (6):e100543.

Chicago/Turabian Style

Salai Madhumathi Parkunan; Roger Astley; Michelle C. Callegan. 2014. "Role of TLR5 and Flagella in Bacillus Intraocular Infection." PLOS ONE 9, no. 6: e100543.

Research article
Published: 21 February 2014 in Current Eye Research
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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.

ACS Style

Jonathan J. Hunt; Roger Astley; Nanette Wheatley; Jin-Town Wang; Michelle C. Callegan. TLR4 Contributes to the Host Response toKlebsiellaIntraocular Infection. Current Eye Research 2014, 39, 790 -802.

AMA Style

Jonathan J. Hunt, Roger Astley, Nanette Wheatley, Jin-Town Wang, Michelle C. Callegan. TLR4 Contributes to the Host Response toKlebsiellaIntraocular Infection. Current Eye Research. 2014; 39 (8):790-802.

Chicago/Turabian Style

Jonathan J. Hunt; Roger Astley; Nanette Wheatley; Jin-Town Wang; Michelle C. Callegan. 2014. "TLR4 Contributes to the Host Response toKlebsiellaIntraocular Infection." Current Eye Research 39, no. 8: 790-802.

Research article
Published: 06 December 2011 in PLoS ONE
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Bacillus cereus causes a uniquely rapid and blinding intraocular infection, endophthalmitis. B. cereus replicates in the eye, synthesizes numerous toxins, and incites explosive intraocular inflammation. The mechanisms involved in the rapid and explosive intraocular immune response have not been addressed. Because Toll-like receptors (TLRs) are integral to the initial recognition of organisms during infection, we hypothesized that the uniquely explosive immune response observed during B. cereus endophthalmitis is directly influenced by the presence of TLR2, a known Gram-positive pathogen recognition receptor. To address this hypothesis, we compared the courses of experimental B. cereus endophthalmitis in wild type C57BL/6J mice to that of age-matched homozygous TLR2-/- mice. Output parameters included analysis of bacterial growth, inflammatory cell (PMN) infiltration, cytokine/chemokine kinetics, retinal function testing, and histology, with N≥4 eyes/assay/time point/mouse strain. B. cereus grew at similar rates to108 CFU/eye by 12 h, regardless of the mouse strain. Retinal function was preserved to a greater degree in infected TLR2-/- eyes compared to that of infected wild type eyes, but infected eyes of both mouse strains lost significant function. Retinal architecture was preserved in infected TLR2-/- eyes, with limited retinal and vitreal cellular infiltration compared to that of infected wild type eyes. Ocular myeloperoxidase activities corroborated these results. In general, TNFα, IFNγ, IL6, and KC were detected in greater concentrations in infected wild type eyes than in infected TLR2-/- eyes. The absence of TLR2 resulted in decreased intraocular proinflammatory cytokine/chemokine levels and altered recruitment of inflammatory cells into the eye, resulting in less intraocular inflammation and preservation of retinal architecture, and a slightly greater degree of retinal function. These results demonstrate TLR2 is an important component of the initial ocular response to B. cereus endophthalmitis.

ACS Style

Billy D. Novosad; Roger Astley; Michelle C. Callegan. Role of Toll-Like Receptor (TLR) 2 in Experimental Bacillus cereus Endophthalmitis. PLoS ONE 2011, 6, e28619 .

AMA Style

Billy D. Novosad, Roger Astley, Michelle C. Callegan. Role of Toll-Like Receptor (TLR) 2 in Experimental Bacillus cereus Endophthalmitis. PLoS ONE. 2011; 6 (12):e28619.

Chicago/Turabian Style

Billy D. Novosad; Roger Astley; Michelle C. Callegan. 2011. "Role of Toll-Like Receptor (TLR) 2 in Experimental Bacillus cereus Endophthalmitis." PLoS ONE 6, no. 12: e28619.

Journal article
Published: 01 February 2008 in Cornea
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To define the histopathology of Salzmann nodular degeneration and suggest potential mechanisms involved in its pathogenesis. Archived corneal biopsy specimens from 5 patients with Salzmann nodular degeneration were evaluated by chemical and immunohistochemical staining to describe the structure of the Salzmann nodules and phenotypes of nodule epithelium and stromal cells. Each Salzmann nodule appeared as a hypercellular mound of extracellular matrix located between a thinned corneal epithelium and a fragmented Bowman layer. Stromal cells within each nodule stained positively for vimentin, consistent with a fibroblast phenotype, whereas the epithelial cells overlying each nodule were positive for matrix metalloproteinase-2 and negative for matrix metalloproteinase-9. The observed epithelial expression of matrix metalloproteinase-2 overlying Salzmann nodules is consistent with chronic epithelial wounding in the disorder but does not identify a cause-effect relationship. Salzmann nodules might develop because of enzymatic disruption of the Bowman layer, anterior migration and proliferation of keratocytes, and secondary deposition of extracellular matrix. Alternatively, desiccation secondary to the elevation of the nodule might induce increased epithelial metalloproteinase expression.

ACS Style

Donald U Stone; Roger A Astley; Robert P Shaver; James Chodosh. Histopathology of Salzmann Nodular Corneal Degeneration. Cornea 2008, 27, 148 -151.

AMA Style

Donald U Stone, Roger A Astley, Robert P Shaver, James Chodosh. Histopathology of Salzmann Nodular Corneal Degeneration. Cornea. 2008; 27 (2):148-151.

Chicago/Turabian Style

Donald U Stone; Roger A Astley; Robert P Shaver; James Chodosh. 2008. "Histopathology of Salzmann Nodular Corneal Degeneration." Cornea 27, no. 2: 148-151.

Journal article
Published: 01 September 2007 in The Anatomical Record
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We report for the first time, the detection of conjunctival lymphoid follicles (CLF) in the eyes of New World rodents. CLF were found in 7 of the 15 species examined, 6 of the 10 genera, and in at least one individual in four families of rodents. These follicles are dense collections of leukocytes in the conjunctival substantia propria with a thinned overlying epithelium lacking in goblet cells. Although the precise location of CLF within the conjunctiva varied from species to species, all CLF were found in the fornix of the conjunctival sac. In general, size and complexity of CLF varied with the size of the eye; the larger the eye, the larger and more complex the CLF. Our findings also reveal that some species of New World rodents, like the majority of Old World rodents examined in this and previous studies might lack CLF. However, until larger samples are examined, this is difficult to state with certainty. Consequently, the presence/absence of CLF at this point might not be informative for phylogenetic comparisons. Our findings also suggest the deer mouse, Peromyscus maniculatus, might serve as a useful model species for studying ocular infections and immunology of the eye.

ACS Style

Roger A. Astley; James Chodosh; William Caire; Gregory M. Wilson. Conjunctival Lymphoid Follicles in New World Rodents. The Anatomical Record 2007, 290, 1190 -1194.

AMA Style

Roger A. Astley, James Chodosh, William Caire, Gregory M. Wilson. Conjunctival Lymphoid Follicles in New World Rodents. The Anatomical Record. 2007; 290 (9):1190-1194.

Chicago/Turabian Style

Roger A. Astley; James Chodosh; William Caire; Gregory M. Wilson. 2007. "Conjunctival Lymphoid Follicles in New World Rodents." The Anatomical Record 290, no. 9: 1190-1194.

Journal article
Published: 01 February 2007 in Investigative Opthalmology & Visual Science
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Purpose. To develop a mouse model of adenoviral keratitis that will allow further study of viral and host pathogenic mechanisms.

ACS Style

Ashish Chintakuntlawar; Roger Astley; James Chodosh. Adenovirus Type 37 Keratitis in the C57BL/6J Mouse. Investigative Opthalmology & Visual Science 2007, 48, 781 -788.

AMA Style

Ashish Chintakuntlawar, Roger Astley, James Chodosh. Adenovirus Type 37 Keratitis in the C57BL/6J Mouse. Investigative Opthalmology & Visual Science. 2007; 48 (2):781-788.

Chicago/Turabian Style

Ashish Chintakuntlawar; Roger Astley; James Chodosh. 2007. "Adenovirus Type 37 Keratitis in the C57BL/6J Mouse." Investigative Opthalmology & Visual Science 48, no. 2: 781-788.

Comparative study
Published: 01 April 2005 in Cornea
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To determine whether conjunctival lymphoid follicles are preferential sites for uptake of foreign material in the preocular tear film. Iron oxide suspension was applied to the eyes of New Zealand white rabbits for selected times, and the conjunctiva was examined histochemically for the presence of iron. Iron was observed by histochemical staining within conjunctival follicle–associated epithelium at 1 hour and deep within the follicles at 4 hours after exposure. Iron was not seen within nonfollicular conjunctival epithelium or underlying substantia propria at any time after iron oxide application. Iron oxide in the preocular tear film is taken up preferentially by conjunctival lymphoid tissue, supporting the hypothesis that mammalian conjunctival lymphoid follicles may participate in the acquired immune response to pathogens in the preocular tear film.

ACS Style

Roger A Astley; James Chodosh. Selective Uptake of Iron Oxide by Rabbit Conjunctival Lymphoid Follicles. Cornea 2005, 24, 334 -336.

AMA Style

Roger A Astley, James Chodosh. Selective Uptake of Iron Oxide by Rabbit Conjunctival Lymphoid Follicles. Cornea. 2005; 24 (3):334-336.

Chicago/Turabian Style

Roger A Astley; James Chodosh. 2005. "Selective Uptake of Iron Oxide by Rabbit Conjunctival Lymphoid Follicles." Cornea 24, no. 3: 334-336.

Journal article
Published: 01 June 2003 in Experimental Eye Research
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ACS Style

Roger A. Astley; Ronald C. Kennedy; James Chodosh. Structural and cellular architecture of conjunctival lymphoid follicles in the baboon (Papio anubis). Experimental Eye Research 2003, 76, 685 -694.

AMA Style

Roger A. Astley, Ronald C. Kennedy, James Chodosh. Structural and cellular architecture of conjunctival lymphoid follicles in the baboon (Papio anubis). Experimental Eye Research. 2003; 76 (6):685-694.

Chicago/Turabian Style

Roger A. Astley; Ronald C. Kennedy; James Chodosh. 2003. "Structural and cellular architecture of conjunctival lymphoid follicles in the baboon (Papio anubis)." Experimental Eye Research 76, no. 6: 685-694.