Document Detail


The use of antimicrobial peptides in ophthalmology: an experimental study in corneal preservation and the management of bacterial keratitis.
MedLine Citation:
PMID:  12545697     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Bacterial keratitis is an ocular infection with the potential to cause significant visual impairment. Increasing patterns of antibiotic resistance have necessitated the development of new antimicrobial agents for use in bacterial keratitis and other serious ocular infections. With a view to exploring the use of novel antimicrobial peptides in the management of ocular infection, we performed a series of experiments using synthetic antimicrobial peptides designed for the eradication of common and serious ophthalmic pathogens. METHODS: Experiments were performed with three clinical ocular isolates--Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis--in three experimental settings: (1) in vitro in a controlled system of 10 mM sodium phosphate buffer, (2) in vitro in modified chondroitin sulfate-based corneal preservation media (Optisol), and (3) in an in vivo animal model (rabbit) simulating bacterial keratitis. In all cases, outcomes were measured by quantitative microbiological techniques. RESULTS: The candidate peptides (CCI A, B, and C and COL-1) produced a total reduction of the test pathogens in phosphate buffered saline. In modified Optisol, the peptides were effective against S epidermidis at all temperatures, demonstrated augmented activity at 23 degrees C against the gram-positive organisms, but were ineffective against P aeruginosa. The addition of EDTA to the medium augmented the killing of P aeruginosa but made no difference in the reduction of gram-positive organisms. In an in vivo rabbit model of Pseudomonas keratitis, COL-1 demonstrated neither clinical nor microbicidal efficacy and appeared to have a very narrow dosage range, outside of which it appeared to be toxic to the ocular surface. CONCLUSION: Our data indicate that the antimicrobial peptides we tested were effective in vitro but not in vivo. In an age of increasing antibiotic resistance, antimicrobial peptides, developed over millions of years as innate defense mechanisms by plants and animals, may have significant potential for development as topical agents for the management of severe bacterial keratitis. However, modifications of the peptides, the drug delivery systems, or both, will be necessary for effective clinical application.
Authors:
Mark J Mannis
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Transactions of the American Ophthalmological Society     Volume:  100     ISSN:  0065-9533     ISO Abbreviation:  Trans Am Ophthalmol Soc     Publication Date:  2002  
Date Detail:
Created Date:  2003-01-27     Completed Date:  2003-03-03     Revised Date:  2010-09-14    
Medline Journal Info:
Nlm Unique ID:  7506106     Medline TA:  Trans Am Ophthalmol Soc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  243-71     Citation Subset:  IM    
Affiliation:
Cornea Research Laboratory, Department of Ophthalmology, University of California, Davis, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Bacterial Agents / chemistry,  pharmacology,  therapeutic use*
Chondroitin Sulfates
Complex Mixtures
Cornea / drug effects*,  microbiology
Culture Media, Serum-Free
Dextrans
Eye Infections, Bacterial / drug therapy*,  microbiology
Gentamicins
Humans
Keratitis / drug therapy*,  microbiology
Organ Preservation
Peptide Fragments / chemical synthesis,  chemistry
Pseudomonas Infections / drug therapy*,  microbiology
Pseudomonas aeruginosa / drug effects,  isolation & purification
Rabbits
Sheep
Staphylococcal Infections / drug therapy*,  microbiology
Staphylococcus aureus / drug effects,  isolation & purification
Staphylococcus epidermidis / drug effects,  isolation & purification
Chemical
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Complex Mixtures; 0/Culture Media, Serum-Free; 0/Gentamicins; 0/Peptide Fragments; 9004-54-0/Dextrans; 9007-28-7/Chondroitin Sulfates; 97794-22-4/Optisol
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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