title: Antimicrobial Blue Light Therapy for Infectious Keratitis: Ex Vivo and In Vivo Studies.
abstract: To investigate the effectiveness of antimicrobial blue light (aBL) as an alternative or adjunctive therapeutic for infectious keratitis.
  
  
  
  We developed an ex vivo rabbit model and an in vivo mouse model of infectious keratitis. A bioluminescent strain of Pseudomonas aeruginosa was used as the causative pathogen, allowing noninvasive monitoring of the extent of infection in real time via bioluminescence imaging. Quantitation of bacterial luminescence was correlated to colony-forming units (CFU). Using the ex vivo and in vivo models, the effectiveness of aBL (415 nm) for the treatment of keratitis was evaluated as a function of radiant exposure when aBL was delivered at 6 or 24 hours after bacterial inoculation. The aBL exposures calculated to reach the retina were compared to the American National Standards Institute standards to estimate aBL retinal safety.
  
  
  
  Pseudomonas aeruginosa keratitis fully developed in both the ex vivo and in vivo models at 24 hours post inoculation. Bacterial luminescence in the infected corneas correlated linearly to CFU (R2 = 0.921). Bacterial burden in the infected corneas was rapidly and significantly reduced (>2-log10) both ex vivo and in vivo after a single exposure of aBL. Recurrence of infection was observed in the aBL-treated mice at 24 hours after aBL exposure. The aBL toxicity to the retina is largely dependent on the aBL transmission of the cornea.
  
  
  
  Antimicrobial blue light is a potential alternative or adjunctive therapeutic for infectious keratitis. Further studies of corneal and retinal safety using large animal models, in which the ocular anatomies are similar to that of humans, are warranted.
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States 2Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Irene E
authors.initials: IE
authors.lastname: Kochevar
authors.affiliation: Department of Medicine, Mount Auburn Hospital, Harvard Medical School, Cambridge, Massachusetts, United States 4School of Medicine, Tufts University, Boston, Massachusetts, United States.
authors.forename: Irmgard
authors.initials: I
authors.lastname: Behlau
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Wang
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States 5Department of Laser Medicine, Chinese PLA General Hospital, Beijing, China.
authors.forename: Yucheng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Sun
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hamblin
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Tianhong
authors.initials: T
authors.lastname: Dai
mesh_terms: D000818:Animals; D015169:Colony Count, Microbial; D003315:Cornea / Q000382:microbiology* / Q000473:pathology; D004195:Disease Models, Animal; D015818:Eye Infections, Bacterial / Q000175:diagnosis / Q000382:microbiology / Q000628:therapy*; D005260:Female; D005500:Follow-Up Studies; D007634:Keratitis / Q000175:diagnosis / Q000382:microbiology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D010789:Phototherapy / Q000379:methods*; D011552:Pseudomonas Infections / Q000175:diagnosis / Q000382:microbiology / Q000628:therapy*; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification*; D011817:Rabbits