Treatment of alkali-injured rabbit corneas with a synthetic inhibitor of matrix metalloproteinases

G. S. Schultz, S. Strelow, G. A. Stern, N. Chegini, M. B. Grant, R. E. Galardy, D. Grobelny, J. J. Rowsey, K. Stonecipher, V. Parmley, P. T. Khaw

Research output: Contribution to journalArticle

103 Scopus citations

Abstract

Healing of corneal alkali injuries remains a severe clinical challenge. The authors evaluated the effect of a new synthetic inhibitor of matrix metalloproteinases (GM6001 or N-[2(R)-2-(hydroxamido carbonylmethyl)-4- methylpentanoyl]-L-tryptophane methylamide) on preventing ulceration of rabbit corneas after alkali injury. Topical treatment of corneas with severe alkali injuries with 400 μg/ml or 40 μg/ml GM6001 alone prevented ulceration for 28 days, although 8 of 10 corneas treated with vehicle perforated. Corneas treated with 4 μg/ml GM6001 had midstromal depth ulcers. Corneas treated with 400 μg/ml of GM6001 contained very few inflammatory cells and had significantly reduced vessel ingrowth compared with vehicle- treated corneas. Epithelial regeneration after moderate alkali injuries also was investigated. Persistent epithelial defects developed 4 days after moderate alkali injury in rabbit corneas treated with vehicle and progressively increased to an average of 20% of the original 6 mm diameter wound by 27 days after moderate alkali injury. By contrast, epithelial regeneration was complete and persisted for 21 days for corneas treated with a formulation containing GM6001 (400 μg/ml), epidermal growth factor (10 μg/ml), fibronectin (500 μg/ml), and aprotinin (400 μg/ml). Sporadic punctate staining developed in 20% of the corneas treated with the combination of agents between days 21-28 after moderate alkali injury. These results demonstrate that topical application of GM6001 prevented corneal ulceration after severe alkali injury and that a combination containing GM6001, epidermal growth factor, fibronectin, and aprotinin promoted stable regeneration of corneal epithelium after moderate alkali injury.

Original languageEnglish (US)
Pages (from-to)3325-3331
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume33
Issue number12
StatePublished - Jan 1 1992

Keywords

  • aprotinin
  • collagen
  • cornea
  • epidermal growth factor
  • fibronectin
  • matrix metalloproteinase inhibitor
  • ulcer

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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    Schultz, G. S., Strelow, S., Stern, G. A., Chegini, N., Grant, M. B., Galardy, R. E., Grobelny, D., Rowsey, J. J., Stonecipher, K., Parmley, V., & Khaw, P. T. (1992). Treatment of alkali-injured rabbit corneas with a synthetic inhibitor of matrix metalloproteinases. Investigative Ophthalmology and Visual Science, 33(12), 3325-3331.