June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Differential effects of E. coli versus S. typhimurium derived lipopolysaccharides on development of uveitis in the rabbit
Author Affiliations & Notes
  • Marianna Bacellar-Galdino
    Research and Development Division, Experimentica Ltd, Forest Park, Illinois, United States
    Ophthalmology and Molecular Pharmacology & Neuroscience, Loyola University Chicago, Maywood, Illinois, United States
  • Nathaniel E Pappenhagen
    Research and Development Division, Experimentica Ltd, Forest Park, Illinois, United States
  • Simon Kaja
    Research and Development Division, Experimentica Ltd, Forest Park, Illinois, United States
    Ophthalmology and Molecular Pharmacology & Neuroscience, Loyola University Chicago, Maywood, Illinois, United States
  • Footnotes
    Commercial Relationships   Marianna Bacellar-Galdino None; Nathaniel Pappenhagen None; Simon Kaja None
  • Footnotes
    Support  Experimentica Ltd.; Dr. John P. and Therese E. Mulcahy Endowed Professorship in Ophthalmology
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 143. doi:
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    • Get Citation

      Marianna Bacellar-Galdino, Nathaniel E Pappenhagen, Simon Kaja; Differential effects of E. coli versus S. typhimurium derived lipopolysaccharides on development of uveitis in the rabbit. Invest. Ophthalmol. Vis. Sci. 2023;64(8):143.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Uveitis describes the inflammation of the uveal tissues of the eye. Posterior uveitis, the inflammation of the choroid, can affect the retina and optic nerve and result in blindness. Lipopolysaccharide (LPS) is routinely used to induce a phenotype of infectious uveitis in rabbits. However, descriptions of the LPS-induced uveitis models differ greatly in the literature. The purpose of this study was to standardize the LPS-induced model for infectious uveitis in pigmented Dutch Belted rabbits using LPS derived from Escherichia coli and Salmonella typhimurium.

Methods : LPS derived from E. coli or S. typhimurium was delivered to Dutch Belted rabbits by single bilateral intravitreal injection (50 µl). Slit-lamp ophthalmic exams were performed after LPS injection to monitor pathology (vitreous haze and retinal involvement) and evaluated using the SPOTS system. Fundus pictures were taken using a hand-held fundus camera. In a separate experiment, rabbits (n=4) were injected intravitreally with 50 µl LPS derived from S. typhimurium on Day -6. On Day 0, one eye remained untreated, while the other eye received a single intravitreal injection (50 µl) of dexamethasone. Ophthalmic exams were performed on Days 0, 2 and 6. Rabbits for sacrificed on Day 6 and eyes processed for histopathology.

Results : Both sources of LPS resulted in ocular phenotypes of posterior uveitis. Notably, vitreous cloudiness after E. coli injection began dissipating after 14 days. In contrast, S. typhimurium resulted in vitreous cloudiness that peaked at Day 7 and was sustained through Day 21. Intravitreally-delivered dexamethasone injected 6 days after LPS insult significantly reduced vitreous cloudiness on Day 6 (p<0.001, n = 8). Inflammation was limited to the posterior segments, as hyperemia and chemosis scores were not affected by dexamethasone. Resolution of inflammation by dexamethasone was confirmed by fundus imaging.

Conclusions : Intravitreal delivery of LPS from S. typhimurium resulted in a more severe and sustained pathology of infectious uveitis in Dutch Belted rabbits compared with LPS from E. coli. The phenotype elicited by S. typhimurium LPS is useful for drug discovery studies evaluating pharmacological efficacy of novel drug candidates for uveitis, especially sustained-release formulations and implants. Our data highlight the need for the detailed reporting of LPS sources for ocular studies.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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