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James P. Luton Endowed Chair in Ophthalmology
Edith Kinney Gaylord Presidential Professor
Departments of Ophthalmology, Microbiology & Immunology
Associate Director for Research, Oklahoma Center for Neuroscience
Telephone: (405) 271-3674
Fax: (405) 271-8128

updated January 2016

The Callegan Lab | Research Interests | Publications and Research Support

Welcome to the Callegan Lab!

Take a look at the Callegan Lab here. Members of the lab include:

Dr. Phillip Coburn Assistant Professor of Research Ocular Bacterial Pathogenesis
Madhu Parkunan Microbiology/Immunology Graduate Student Innate Immune Effectors in Endophthalmitis
Roger Astley Research Technician Pathogenesis of Endophthalmitis
Austin LaGrow Research Technician Pathogenesis of Endophthalmitis
Dr. Kris Miller Professor, Department of Cell Biology Pathogenesis of Endophthalmitis

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--Present Focus of Research--

Bacillus cereus is an insidious ocular pathogen, causing a rapid and fulminant endophthalmitis that invariably leads to blindness within one to two days. Despite aggressive antibiotic and surgical intervention, B. cereus endophthalmitis has a relatively poor prognosis. There is presently no universal therapeutic regimen for successful treatment of Bacillus and other forms of severe bacterial endophthalmitis. Clinicians and researchers have attributed the virulence of B. cereus and other virulent endophthalmitis pathogens to toxin production. For Bacillus however, toxins are not the complete story. Bacillus is also motile, and migrates throughout the eye in a short period of time, inciting an explosive intraocular inflammatory response in its wake. This inflammatory response is likely the result of breakdown of the protective blood ocular barrier in response to infection, the triggers of which are presently being investigated. In addition, during infection, retinal architecture collapses and retinal function drops precipitously. We hypothesize that either Bacillus or its toxins (or both) target specific cells in the retina that are involved in protection by the blood ocular barrier (retinal pigment epithelial [RPE] cells) or retinal function itself (Muller cells, photoreceptor cells), leading to the detrimental effects observed during infection. Since the ultimate goal of therapy is to kill offending organisms, arrest inflammation, and preserve organ function, an important goal is to develop more effective therapeutic regimens, with newer antibiotics, anti-inflammatory agents, and/or novel drugs that target bacteria- and host-derived virulence factors in order to prevent blindness.

--Relevant findings and ongoing research projects--

A list of research projects tailored for graduate, medical, and undergraduate students, and ophthalmology residents and fellows can be found here.


The murine model of Bacillus endophthalmitis is being used to analyze the acute stage of posterior segment inflammation. Proinflammatory cytokines are detected in the eye just prior to PMN influx into the posterior segment. These cytokines likely recruit PMNs to the interior of the eye. Cytokine and anti-cytokine therapeutics are being analyzed to determine the role of TNFa in bacterial endophthalmitis. Induction of these cytokines by Toll-like receptor interactions are also being analyzed using transgenic mice deficient in specific receptors and their downstream effectors.

Early changes in retinal function, as measured by electroretinography (ERG), include a stark increase in b-wave latency several hours before the precipitous drop in b-wave amplitude. These findings suggest alteration in the function of cells responsible for the b-wave during the early stages of infection. Preliminary results also indicate an early change to a-wave function during infection, suggesting photoreceptor cell dysfunction. By analyzing the effects of infection and toxins on specific retinal cell types we hope to characterize the cellular mechanisms of vision loss during the early stages of infection.

During the acute stage of inflammation, the blood retinal barrier becomes permeable, resulting in migration of larger molecules and cells into the retina and vitreous. We are analyzing ocular permeability at the level of the retinal pigment epithelium (RPE) to determine whether disruption of tight junctions or cytoskeletal rearrangements within blood retinal barrier contributes to permeability, and what toxins are involved in these events.

No universal therapeutic regimen exists for the treatment of severe bacterial endophthalmitis. Bacillus endophthalmitis is particularly devastating, resulting in blindness or loss of the eye in the majority of cases. We are now testing newer and more potent antibiotics, anti-inflammatory drugs, and earlier drug delivery to improve therapeutic outcomes of Bacillus endophthalmitis. Our results suggest that intravitreal antibiotics should be administered as early as possible to save useful vision, especially if patients suffer from "dirty" penetrating injuries.

Bacillus toxins under the control of the global regulator plcR contribute significantly to Bacillus endophthalmitis pathogenesis. Endophthalmitis caused by plcR knockout strains is highly attenuated. These infections result in at least 20% of retained retinal function throughout 36 hours of infection and a muted inflammatory response that does not achieve the explosive response observed in wild type Bacillus endophthalmitis. Blockade of the autoinducing peptide PapR as a form of adjunct therapy is presently under investigation.

Bacillus migrates into all parts of the eye within 18 hours. Bacillus strains defective in motility do not migrate within the eye, replicate slower, are defective in toxin production, and cause infections that are highly attenuated for the first 24 hours. Characterization of the attenuation of infection by motility blockade is presently underway.

Components of the Bacillus cell wall incite intraocular inflammation in sterile endophthalmitis models, but do not affect retinal function. Individual bacterial cell wall-associated constituents (i.e. peptidoglycan, teichoic acid, capsules, S-layer) are being analyzed as inducers of acute intraocular inflammation. Bacterial component recognition by retinal cells is being analyzed using toll-like receptor knockout mice.

The role of Bacillus proteases in endophthalmitis has not been determined. Bacillus strains that lack the immune inhibitor metalloprotease InhA1 are more virulent than wild type parental strains. Further studies are underway to determine why the absence of these proteases enhances virulence.


Endogenous endophthalmitis (EE) results from metastatic spread of bacteria into the eye from a distant site of infection. Those afflicted by EE tend to be immunocompromised individuals, including elderly diabetics. EE is particularly devastating because it has the capacity to blind bilaterally. We are developing experimental models of EE caused by both Gram-negative and Gram-positive bacteria that will be used to analyze the mechanisms of bacterial migration across the blood ocular barrier and therapies designed to block these events.

Klebsiella pneumoniae and Staphylococcus aureus are devastating pathogens of the eye, most often acquired following primary infection at a distant site in both immunocompetent and immunocompromised individuals. We are presently analyzing the specific virulence factors involved in persistent and systemic infection, prior to migration into the eye, and those responsible for migration of these organisms across the blood retinal barrier.

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Full list of publications at MyNCBI Bibliography can be found here.

Current Research Support

PI -- "Nanotherapeutics for Treatment of Ocular Infections" NIH R01EY025947-01 (09/10/15-08/09/18).

PI – “Vascular Permeability in Ocular Infections” NIH R01EY024140-03 (01/01/14-12/31/17).

Director, Live Animal Imaging and Functional Analysis Module – “Core Grant for Vision Research” (RE Anderson, PI) NIH CORE grant P30 (9/11-8/15)

Past Research Support

PI – “New Models of Endogenous Bacterial Endophthalmitis” NIH R21 EY022466-01A1 (12/01/12-11/30/14 +1)

Co-I -- "Condensin Dependent Potentiation of Antibiotics” (Rybenkov, PI [OU Norman]) -- OCAST HR-14-042 (subaward 7/1/14-6/30/16)

PI -- Pathogenic Mechanisms of  Bacillus cereus  Endophthalmitis; NIH/NEI R01 EY012985 (09/00-08/13+1) and EY012985-S1 (09/01/12-08/31/13)

PI -- Department of Defense CDMRP Award: Improved Therapeutic Regimens for Post-Traumatic Ocular Infections. (4/07-4/11+1)

PI -- Research Grants from Allergan Inc. (Irvine CA)

PI -- Research Grants from Charlesson Inc. LLC (Oklahoma City OK)

PI -- Enhancements in Imaging in Vision Research; Presbyterian Health Foundation 07/08-06/09

PI -- Lew R. Wasserman Award, Research to Prevent Blindness Inc. 07/06-06/07.

 "Electroretinographic Equipment for Vision Research" - Presbyterian Health Foundation, OUHSC

"Technological Enhancements for Ocular Infectious Disease Research" - Administrative Supplement to R01 EY12985 07/02-05/04

Research to Prevent Blindness Career Development Award 07/00-06/04

"Role of Adherence in Keratitis"; NIH/NEI R01 EY11648 (Co-I, M.S. Gilmore PI) 

"The Role of Bacterial Motility in Bacillus cereus Endophthalmitis"; Fight For Sight/Prevent Blindness America

"The Role of Toxins in the Pathogenesis of Bacillus cereus Endophthalmitis"; University of Oklahoma Medical Alumni Association

"Role of Toxins in Bacillus cereus Endophthalmitis"; National Research Service Award (F32) EY06813-02  


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