June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Antimicrobial and anti-inflammatory effect of genipin in a rabbit model of Staphylococcus aureus and Pseudomonas aeruginosa keratitis
Author Affiliations & Notes
  • Marcela Huertas-Bello
    Ophthalmology, Universidad Nacional de Colombia Facultad de Medicina, Bogota, Cundinamarca, Colombia
  • Jerson Andrés Cuéllar Sáenz
    Department of Animal Health, Faculty of Veterinary Medicine and Zootechnics, Universidad Nacional de Colombia, Bogota, Bogota, Colombia
  • Cristian N Rodriguez
    Department of Microbiology, Universidad Nacional de Colombia Facultad de Medicina, Bogota, Cundinamarca, Colombia
  • Jesús Alfredo Cortés Vecino
    Department of Animal Health, Faculty of Veterinary Medicine and Zootechnics, Universidad Nacional de Colombia, Bogota, Bogota, Colombia
  • Myriam L Navarrete
    Department of Microbiology, Universidad Nacional de Colombia Facultad de Medicina, Bogota, Cundinamarca, Colombia
  • Marcel Yecid Avila
    Ophthalmology, Universidad Nacional de Colombia Facultad de Medicina, Bogota, Cundinamarca, Colombia
  • Elena Koudouna
    Structural Biophysics Group, School of Optometry and Vision Sciences, Cardiff University, Cardiff, Cardiff, United Kingdom
    Ophthalmology, Universidad Nacional de Colombia Facultad de Medicina, Bogota, Cundinamarca, Colombia
  • Footnotes
    Commercial Relationships   Marcela Huertas-Bello None; Jerson Andrés Cuéllar Sáenz None; Cristian N Rodriguez None; Jesús Alfredo Cortés Vecino None; Myriam L Navarrete None; Marcel Yecid Avila None; Elena Koudouna None
  • Footnotes
    Support  European Commision Horizon 2020 Grant 793328
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 3298. doi:
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      Marcela Huertas-Bello, Jerson Andrés Cuéllar Sáenz, Cristian N Rodriguez, Jesús Alfredo Cortés Vecino, Myriam L Navarrete, Marcel Yecid Avila, Elena Koudouna; Antimicrobial and anti-inflammatory effect of genipin in a rabbit model of Staphylococcus aureus and Pseudomonas aeruginosa keratitis. Invest. Ophthalmol. Vis. Sci. 2023;64(8):3298.

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

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Abstract

Purpose : The treatment of infectious keratitis is challenging due to diagnostic delays, bacterial resistance, and severe sight threatening sequelae. Our group previously demonstrated that corneal crosslinking with genipin had antimicrobial effects in an ex-vivo corneal model. In this study, we evaluated the antimicrobial and inflammatory effects of genipin in a rabbit model of S. aureus and P. aeruginosa keratitis.

Methods : S. aureus (ATCC 25923) or P. aeruginosa (ATCC 27853) strains were intrastromally injected. Twenty rabbits were equally divided into four treatment groups: S. aureus + vehicle (group 1), S. aureus + genipin (group 2), P. aeruginosa + vehicle (group 3), and P. aeruginosa + genipin (group 4). Uninfected, untreated eyes were the healthy control group (group 5). Genipin at 6 and 24 hours post-inoculation was administrated. Clinical evaluation was performed before and after each treatment. Corneal homogenates were used to calculate the log number of colony-forming units (log CFU) per cornea. Expression of selected pro- and anti-inflammatory cytokines, growth factors, and matrix metalloproteinases (MMPs) was assayed by quantitative polymerase chain reaction.

Results : All vehicle-treated eyes had higher clinical scores. Corneal perforation occurred in one vehicle-treated eye of the S. aureus keratitis model and in two vehicle-treated eyes in the P. aeruginosa model. None of the genipin-treated eyes progressed to corneal perforation. In the S. aureus keratitis model, genipin treatment significantly reduced the bacterial load compared to the vehicle treated group (mean log 3.42 ± 0.65 vs 5.64 ± 0.93 CFU, respectively; p=0.0142). No statistically significant differences were found in the CFU between vehicle and genipin treatment groups in the P. aeruginosa model (mean log 3.42 ± 0.55 versus 3.01 ± 0.68 CFU, respectively). The inflammatory response was distinct in each model and genipin treatment resulted in significantly decreased levels of MMP9, IL1B, IL8, IL15 and IL1RA. In the S. aureus model, genipin treatment further demonstrated significant reduction in the levels of MMP2, IL6, TNFα, TGFβ and IFNγ.

Conclusions : Corneal crosslinking with genipin is a possible therapeutic alternative for infectious bacterial keratitis supported by the promising results of this investigation. Further studies are needed to clarify the mechanism of action of genipin.

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

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