Evaluation of tear film proteinases in horses with ulcerative keratitis

Abstract

Ulcerative keratitis is a common and potentially blinding ocular disease of horses, capable of progressing to corneal perforation in as little as 24 h. This rapid stromal degeneration is mediated in part by exogenous and endogenous proteinases. We measured and compared the concentrations of two matrix metalloproteinases (MMP-2 and MMP-9) and a serine proteinase (neutrophil elastase) present in the precorneal tear film of normal horses and horses with rapidly progressing ulcerative keratitis. Precorneal tear film samples were collected from 23 ulcerated and 21 unaffected eyes of 23 horses with unilateral ulcerative keratitis, and from 33 normal eyes of 17 control horses. MMP-2, MMP-9, and neutrophil elastase were identified by casein and gelatin zymography and quantified by computerized image analysis. Median MMP-9 levels were significantly higher in the precorneal tear film of young control horses vs. older control horses (P = 0.005). Median MMP-2, MMP-9, and neutrophil elastase levels were significantly higher in the precorneal tear film of ulcerated eyes when compared to age-matched normal controls (P = 0.004, P = 0.001, and P = 0.012, respectively). Median MMP-2 levels were also significantly higher in the precorneal tear film of contralateral eyes of affected horses when compared to age-matched normal controls (P = 0.004). No significant differences in median proteinase levels were detected between 'sterile' ulcers and those from which bacteria or mixed infections (bacteria and fungi) were isolated. However, median MMP-2 and neutrophil elastase levels were significantly higher in the precorneal tear film of eyes with 'sterile' ulcers when compared with ulcerated eyes from which fungi were isolated (P < 0.05). The results of this study support the use of topical antiproteinase therapy which targets both MMPs and serine proteinases in progressive equine ulcerative keratitis.

MMP expression in leaking filtering blebs and tears after glaucoma filtering surgery

“…Acera et al [30] found significantly elevated pro-MMP-9 levels in blepharitis, allergic eye disease, dry eye and conjunctivochalasis. An increased expression of MMP-2 has been demonstrated in chronic inflammatory processes, which can result in the perforation of the cornea in both humans [31] and horses [32,33]. Similarly, the expression of active MMP-2 and -9 correlated with the severity of ulceration or burn trauma [34,35].…”

Ceratomicose em equinos

“…Dentre os diversos fatores aos quais se atribui a elevada incidência de afecções corneais em equinos, elencamse o tamanho do bulbo do olho, seu posicionamento proeminente e lateralizado e atividades físicas dos equinos (STRUBBE et al, 2000;BAKER et al, 2008;WADA et al, 2010). Ainda, a superfície ocular encontrase constantemente exposta a bactérias e fungos.…”

“…A MMP-9 encontra-se presente após danos corneais, induzindo à destruição de estruturas adesivas da membrana basal das células epiteliais, retardando, por conseguinte, a reepitelização corneal (OLLIVIER et al, 2003;BOVELAND et al, 2010). Em córneas ulceradas, a atividade das proteinases encontra-se significativamente aumentada no filme lacrimal pré-corneal (STRUBBE et al, 2000;OLLIVIER et al, 2004).…”

“…Essa enzima degrada colágenos do tipo III e IV, bem como alguns compostos da matriz extracelular, tais como laminina e fibronectina (BERMAN et al,1977;FINI et al, 1992;STRUBBE et al, 2000;OLLIVIER et al, 2003;BROOKS et al, 2004).…”

Equine corneal ulcers – A retrospective evaluation of 78 horses (2008–2011)

“…eine eingeschränkte Sehfähigkeit unter Umständen fatal und kann einen erheblichen wirtschaftlichen Verlust für den Tierhalter bedeuten. Die Therapie von Hornhautulzera stellt eine Herausforderung dar, denn innerhalb kurzer Zeit kann es durch enzymatische Zerstörung des Stromas zu Schäden von großem Ausmaß bis hin zu einer Perforation der Hornhaut kommen (Strubbe et al 2000, Haffner et al 2003, De Linde Henriksen et al, 2012. Eine fundierte Aufklärung der Besitzer hinsichtlich der Behandlungsmöglich-keiten, der Prognose für den Erhalt des Auges und der Sehfä-higkeit sowie der Dauer der Behandlung ist schwierig (Höpp-ner 2007).…”