Corneal Ulceration and the Serum Antiproteases I. α₁-Antitrypsin

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Abstract

Tears which bathe ulcerating human corneas or some inflamed eyes without ulcers have been found to contain significantly raised levels of the serum antiprotease, α₁-antitrypsin (α₁-at). A second serum antiprotease, the α₂-macroglobulin (α₂-m), was detected in the tears from 4 of 6 ulcerating, inflamed corneas but was not detected in tears from 3 inflamed eyes without ulcers. The α₂-m was also not detected in 4 tear samples from 4 normal volunteer subjects. In general, the concentration of α₁-at in tears is increased with the severity of ulceration as determined independently in the clinic. That the rise in α₁-at in tears of ulcer patients may reflect a general increase in vascular permeability to serum proteins, including the antiproteases, is supported by the observation that the ratio of serum albumin to α₁-at is the same in tears from ulcerating and non-ulcerating eyes. Most ulcer patients are genetically normal at the α₁-at locus and elevate tear α₁-at levels without elevating serum levels of α₁-at and antitryptic activity during corneal ulceration. Although the α₁-at has been found to inhibit the major rabbit corneal collagenase, it does not inhibit the corneal collagenase obtained from human keratoplasy tissues. The α₁-m inhibits 3 collagenase fractions from the ulcerating rabbit cornea and does inhibit the human corneal collagenase. The significance of the rise in antiprotease levels in the tears of ulcer patients is not known. If the increased tear levels of α₁-at reflect serum protein leak, as is thought, the antiproteases may also leak from inflamed vessels into the cornea. Although the α₁-at and the α₂-m have been reported to inhibit collagenases and neutral proteases from human polymorphonuclear leukocytes, only the α₁-m was found to inhibit the collagenase from keratoplasty tissues. The inhibitory activities of the antiproteases may account, in part, for the sometime clinical impression that serum arrests corneal ulceration.