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

102 Citations (Scopus)

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 - 1992
Externally publishedYes

Fingerprint

Alkalies
Cornea
Rabbits
Wounds and Injuries
Regeneration
Aprotinin
Fibronectins
Epidermal Growth Factor
HSCH2CH(CH2CH(CH3)2)CO-Phe-Ala-NH2
Corneal Epithelium
N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide
Ulcer
Staining and Labeling

Keywords

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

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Schultz, G. S., Strelow, S., Stern, G. A., Chegini, N., Grant, M. B., Galardy, R. E., ... 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.

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

In: Investigative Ophthalmology and Visual Science, Vol. 33, No. 12, 1992, p. 3325-3331.

Research output: Contribution to journalArticle

Schultz, GS, Strelow, S, Stern, GA, Chegini, N, Grant, MB, Galardy, RE, Grobelny, D, Rowsey, JJ, Stonecipher, K, Parmley, V & Khaw, PT 1992, 'Treatment of alkali-injured rabbit corneas with a synthetic inhibitor of matrix metalloproteinases', Investigative Ophthalmology and Visual Science, vol. 33, no. 12, pp. 3325-3331.
Schultz GS, Strelow S, Stern GA, Chegini N, Grant MB, Galardy RE et al. Treatment of alkali-injured rabbit corneas with a synthetic inhibitor of matrix metalloproteinases. Investigative Ophthalmology and Visual Science. 1992;33(12):3325-3331.
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. / Treatment of alkali-injured rabbit corneas with a synthetic inhibitor of matrix metalloproteinases. In: Investigative Ophthalmology and Visual Science. 1992 ; Vol. 33, No. 12. pp. 3325-3331.
@article{7ba8297b42ec4e1bb5da0849d4decbdd,
title = "Treatment of alkali-injured rabbit corneas with a synthetic inhibitor of matrix metalloproteinases",
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.",
keywords = "aprotinin, collagen, cornea, epidermal growth factor, fibronectin, matrix metalloproteinase inhibitor, ulcer",
author = "Schultz, {G. S.} and S. Strelow and Stern, {G. A.} and N. Chegini and Grant, {M. B.} and Galardy, {R. E.} and D. Grobelny and Rowsey, {J. J.} and K. Stonecipher and V. Parmley and Khaw, {P. T.}",
year = "1992",
language = "English (US)",
volume = "33",
pages = "3325--3331",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "12",

}

TY - JOUR

T1 - Treatment of alkali-injured rabbit corneas with a synthetic inhibitor of matrix metalloproteinases

AU - Schultz, G. S.

AU - Strelow, S.

AU - Stern, G. A.

AU - Chegini, N.

AU - Grant, M. B.

AU - Galardy, R. E.

AU - Grobelny, D.

AU - Rowsey, J. J.

AU - Stonecipher, K.

AU - Parmley, V.

AU - Khaw, P. T.

PY - 1992

Y1 - 1992

N2 - 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.

AB - 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.

KW - aprotinin

KW - collagen

KW - cornea

KW - epidermal growth factor

KW - fibronectin

KW - matrix metalloproteinase inhibitor

KW - ulcer

UR - http://www.scopus.com/inward/record.url?scp=0026463072&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026463072&partnerID=8YFLogxK

M3 - Article

C2 - 1385350

AN - SCOPUS:0026463072

VL - 33

SP - 3325

EP - 3331

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 12

ER -