Plasmin in tear fluid of patients with corneal ulcers: basis for new therapy

Abstract

In a patient with chronic corneal ulcer, resistant to conventional therapy, analysis of tear fluid revealed a high plasmin activity which could be inhibited by aprotinin, an inhibitor of serine proteinases. Therapy with topical aprotinin resulted in rapid epithelialization. After this initial patient, within a period of four months tear fluid specimens of altogether 48 patients with corneal lesions were analyzed, and 32 were found to be positive for proteolytic activity. Of these 18 were treated with topical aprotinin which rapidly promoted corneal epithelial healing. Six of these patients had been treated with conventional therapy for 3-10 weeks but proved to be completely therapy-resistant. Our observations on three successfully treated patients with chemical burns of the cornea indicated appearance of plasmin in tear fluid after a few days correlating with cessation of epithelialization. In all patients, in which tear fluid plasmin activity was followed, the activity disappeared during aprotinin therapy correlating with corneal re-epithelialization. In some patients with low proteolytic activity aprotinin was combined with fibronectin with a beneficial therapeutic effect. No proteolytic activity was found in the tear fluid of control individuals. These preliminary data indicate that in patients with treatment-resistant corneal lesions inhibition of proteolytic activity can assist in epithelial healing. Such an inhibition is likely to be a prerequisite for the proteinase-sensitive cell adhesion proteins such as fibronectin to promote epithelialization.

Ocular irritation leads to the appearance of proteolytic activity in the aqueous humor

“…Similarly as shown for proteolytic activity in tear fluid (Salonen et al 1987;Tervo & van Setten 1989), the proteolytic activity in AH demonstrated on casein agarose could be inhibited by the proteinase inhibitor aprotinin. Although normal rabbit aqueous humor does not seem to contain any proteolytic activity, inhibitors to plasminogen-activator activity such as PAI-1 have been demonstrated in AH (Yedevally et al 1990).…”

“…In the present study the demonstrated caseinolytic activity is referred to also as plasmin-like activity, according to earlier 548 publications (Salonen et al 1987;Tervo & van Setten 1989). Human plasmin (Kabi Diagnostica, Sweden, containing 15 IU/mg) was used as standard.…”

Determination of plasminogen activator activities in normal and pathological human tears. The significance of tear plasminogen activators in the inflammatory and traumatic lesions of the cornea and the conjunctiva

“…In a comparative study we have found that the plasminogen activator activity in normal human tears, when measured with a chromogenic method in the absence of fibrin, was almost completely inhibited by anti-uPA antibody while antitPA antibody did not have s i e c a n t blocking effect (TozsCr & Berta 1990). Salonen et al (1987) detected plasmin in the tears of 48 patients with different corneal lesions. The tear samples were collected with glass capillaries.…”

Urokinase Down-Regulation by Aprotinin in Rabbit Corneal Cells After Photorefractive Keratectomy

“…3,4 Aprotinin has been shown to promote healing of chronic corneal ulcers by inhibiting high plasmin activity in humans. 5 It has helped in the treatment of human eye burns. 6 In contrast, aprotinin at 40 and 1000 KIU/ml neither promoted corneal wound healing nor prevented recurrent epithelial defects in rabbit keratectomy wounds.…”