January 1996
Volume 37, Issue 1
Free
Articles  |   January 1996
Inhibition of pseudomonal ulceration in rabbit corneas by a synthetic matrix metalloproteinase inhibitor.
Author Affiliations
  • J P Barletta
    Department of Ophthalmology, University of Florida School of Medicine, Gainesville, USA.
  • G Angella
    Department of Ophthalmology, University of Florida School of Medicine, Gainesville, USA.
  • K C Balch
    Department of Ophthalmology, University of Florida School of Medicine, Gainesville, USA.
  • H G Dimova
    Department of Ophthalmology, University of Florida School of Medicine, Gainesville, USA.
  • G A Stern
    Department of Ophthalmology, University of Florida School of Medicine, Gainesville, USA.
  • M T Moser
    Department of Ophthalmology, University of Florida School of Medicine, Gainesville, USA.
  • G B van Setten
    Department of Ophthalmology, University of Florida School of Medicine, Gainesville, USA.
  • G S Schultz
    Department of Ophthalmology, University of Florida School of Medicine, Gainesville, USA.
Investigative Ophthalmology & Visual Science January 1996, Vol.37, 20-28. doi:
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      J P Barletta, G Angella, K C Balch, H G Dimova, G A Stern, M T Moser, G B van Setten, G S Schultz; Inhibition of pseudomonal ulceration in rabbit corneas by a synthetic matrix metalloproteinase inhibitor.. Invest. Ophthalmol. Vis. Sci. 1996;37(1):20-28.

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

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Abstract

PURPOSE: To evaluate the effect of the synthetic matrix metalloproteinase inhibitor, Galardin, on proteases produced by Pseudomonas aeruginosa (PA) and on a rabbit model of Pseudomonas keratitis. METHODS: Protease activities of culture broths from Pseudomonas strains PA-28 and W-186 were characterized in vitro by gelatin zymography and by digestion of Azocasein in the presence and absence of Galardin and the serine protease inhibitor, aprotinin. In a noninfectious in vivo experiment, sterile PA culture broth from W-186 was injected intrastromally into rabbit corneas that were treated topically with Galardin or vehicle, then evaluated clinically and histologically. In an infectious in vivo experiment, rabbit corneas were injected with washed PA-28, then treated topically with Galardin or vehicle and clinically scored. RESULTS: Gelatin zymography of culture broth from W-186 and PA-28 detected two proteases that were both inhibited by Galardin. Galardin reduced the digestion of Azocasein by both PA culture broths by 99%, whereas aprotinin did not significantly reduce the protease activity of PA-28 conditioned broth. Intrastromal injection of sterile W-186 culture broth caused rapid corneal destruction that was prevented by topical treatment with Galardin. Intrastromal injection of washed PA-28 bacteria resulted in progressive corneal melting that was significantly (P < 0.005) delayed, but ultimately not prevented, by topical treatment with Galardin. CONCLUSIONS: Pseudomonal protease activity in culture broth consisted predominantly of metalloproteinases and were effectively inhibited by Galardin in vitro. Topical treatment with Galardin prevented destruction of rabbit corneas by bacterial products present in culture broth, and it delayed corneal destruction after injection of PA bacteria. Galardin may be a useful adjuvant when corneal destruction proceeds despite prompt antibiotic treatment.

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