Inhibition of alkali-induced corneal ulceration and perforation by a thiol peptide.
Corneal ulceration and perforation following a severe alkali burn occur as a consequence of collagen destruction by locally released enzymes. A thiol peptide, which recently was shown to be a potent inhibitor of corneal collagenase in vitro, was tested in alkali-burned rabbit corneas to determine its effectiveness in inhibiting corneal ulceration. Following a standard alkali burn to one eye of each rabbit, ten animals were treated topically six times daily and subconjunctivally one time daily with a 1 mM solution of the peptide for a period of 3 weeks. A control group of ten rabbits was administered vehicle only using the same regimen as the experimental group. Corneal ulceration occurred in ten out of ten of the control eyes and seven out of ten progressed to perforation. The experimental group demonstrated ulcerations in four out of nine animals, only one of which was deep (one of nine), and no perforations. There was no significant difference when comparing the onset of ulceration between the two groups, but the difference was significant when comparing the total number of ulcerations (0.02 less than P less than 0.05), deep ulcerations (0.01 less than P less than 0.02) and perforations (0.001 less than P less than 0.01) between the two groups. Histologic examination of the corneas after 3 weeks of treatment revealed that the experimental, thiol-treated corneas that did not ulcerate contained relatively few PMNs, whereas the control corneas demonstrated a marked inflammatory infiltrate in the form of PMNs, most notably at sites of corneal ulceration. These findings demonstrate that a synthetic thiol peptide inhibits alkali-induced corneal ulceration and perforation in vivo.
Burns
F R
FR
Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Kentucky.
Gray
R D
RD
Paterson
C A
CA
D000704:Analysis of Variance; D000818:Animals; D002057:Burns, Chemical / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D016009:Chi-Square Distribution; D003315:Cornea / Q000187:drug effects / Q000473:pathology; D003320:Corneal Ulcer / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004334:Drug Administration Schedule; D005126:Eye Burns / Q000139:chemically induced / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D005260:Female; D007267:Injections; D008297:Male; D003012:Microbial Collagenase / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D010455:Peptides / Q000008:administration & dosage / Q000627:therapeutic use; D011817:Rabbits; D012972:Sodium Hydroxide; D013438:Sulfhydryl Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D014945:Wound Healing / Q000187:drug effects
D010455:Peptides; D013438:Sulfhydryl Compounds; D012972:Sodium Hydroxide; D003012:Microbial Collagenase