Proteinases of the cornea and preocular tear film

Abstract

Maintenance and repair of corneal stromal extracellular matrix (ECM) requires a tightly coordinated balance of ECM synthesis, degradation and remodeling in which proteolytic enzymes (proteinases) perform important functions. There are natural proteinase inhibitors present in preocular tear film (PTF) and cornea simultaneously with proteinases that prevent excessive degradation of normal healthy tissue. Disorders occur when there is an imbalance between proteinases and proteinase inhibitors in favor of the proteinases, causing pathologic degradation of stromal collagen and proteoglycans in the cornea. Two matrix metalloproteinases (MMPs), MMP-2 and MMP-9, are of major importance in terms of remodeling and degradation of the corneal stromal collagen. Immunohistochemical studies have shown different origins of MMP-2 and -9. MMP-2 is synthesized by corneal keratocytes and performs a surveillance function in the normal cornea, becoming locally activated to degrade collagen molecules that occasionally become damaged. Alternatively, MMP-9 may be produced by epithelial cells and polymorphonuclear neutrophils following corneal wounding. Because the cornea is in close contact with the preocular tear film (PTF), proteinases have been evaluated in the PTF. In damaged corneas, total proteolytic activity in the tear fluid was found to be significantly increased compared to normal eyes and contralateral eyes. Studies analyzing the proteolytic activity in serial PTF samples during corneal healing led to the following conclusions: ulcerative keratitis in animals is associated with initially high levels of tear film proteolytic activity, which decrease as ulcers heal; proteinase levels in melting ulcers remain elevated leading to rapid progression of the ulcers. The success of medical and surgical treatment of the corneal ulcers is reflected by the proteolytic activity in tears. In animals, successful treatment leads to a rapid reduction in tear film proteolytic activity that corresponds with the improvement in the clinical signs of corneal ulceration. The in vitro effects of various compounds on proteolytic activity in the tear fluid of animals with ulcerative keratitis have been evaluated and their important inhibitory effects have been confirmed. Because these various compounds utilize different mechanisms to inhibit various families of proteinases, a combination of these proteinase inhibitors may be beneficial.

Corneal ulcerative disease in dogs under primary veterinary care in England: epidemiology and clinical management

“…Epithelial defects that affect the basement membrane and expose the corneal stroma are known as corneal ulcers [2]. Corneal ulcerative disease (CUD) can affect animal welfare by the development of pain, reflex uveitis, perforation and even loss of the eye and possibly also by temporarily or permanently interfering with vision [3, 4].…”

Oxidative Stress in Experimental Rodent Corneas Infected With Aflatoxigenic and Nonaflatoxigenic Aspergillus flavus

“…30 These mechanisms possibly contributed to the markedly severe keratitis noted in aflatoxigenic A. flavus-infected rat corneas, in which the intensity of oxidative stress appeared to exceed that in the other 2 groups. The increased markers of corneal oxidative stress were possibly derived directly from the fungal homogenates, as our data suggest.…”

Architectural and Biochemical Expressions of Mustard Gas Keratopathy: Preclinical Indicators and Pathogenic Mechanisms

“…Whether the MMPs in the AH derive from corneal or adnexal tissues is unknown, but corneal entry due to anterior or posterior boundary dysfunction will further disrupt the stroma and basement membrane. MMPs play a major role in corneal remodeling and have been shown to be modulated in the tear film after ocular SM exposure; additionally, treatment of corneas with the MMP-9 inhibitor doxycycline slows MGK onset [9], [29], [30]. A causal relationship between release of MMP-9 from the corneal epithelium and basement membrane disruption has also been demonstrated [31], [32].…”