Proteolytic mechanisms in corneal ulceration and repair

Fini, M. Elizabeth; Cook, Jacob; Mohan, Royce

doi:10.1007/pl00007449

Cited by 172 publications

(118 citation statements)

References 30 publications

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“…44,46 Gelatinase B has been detected in the corneal basal epithelial cells at the edges of non-healing corneal ulcers in humans. This suggests 31 Garrana et al reported that the expression of metalloproteinase-2 was upregulated in corneas with recurrent erosions. These findings suggest that MMPs may be responsible for the breakdown of the anchoring molecules in the basement membrane during epithelial healing, and this is the basis for the use of inhibitors of MMP in the treatment of RCE.…”

Section: Inhibitors Of Mmpmentioning

confidence: 93%

“…The matrices undergo constant, slow remodelling during health and rapid remodelling during repair. [28][29][30][31][32] Corneal stromal remodelling during wound healing is mediated by a group of zinc containing degradative enzymes known as matrix metalloproteinases (MMPs). 33,34 They appear in a precisely controlled sequence that suggest they perform specific roles.…”

Section: Role Of Mmp Activitymentioning

confidence: 99%

“…43 This approach is based on biochemical evidence implicating increased levels of MMP activity in the pathogenesis of this condition. 31,38,44 Doxycycline has been shown to produce a 70% decrease in the activity of metalloproteinase-9 in unstimulated human corneal epithelial cultures. 45 Both topical steroids and oral doxycycline were reported to decrease the frequency of RCE in one randomised controlled clinical trial.…”

Section: Inhibitors Of Mmpmentioning

confidence: 99%

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Pathogenesis, clinical features and management of recurrent corneal erosions

Ramamurthi

Rahman

Dutton

et al. 2005

Eye

109

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Recurrent corneal erosions (RCE) are common. They are characterised by repeated episodes of pain, difficulty in opening the eyes, watering, and photophobia resulting from poor epithelial adhesion. In the majority of patients with RCE, trauma is the initiating factor. Epithelial, stromal, and endothelial corneal dystrophies have all been described in association with RCE. Other causes that may lead to RCE include chemical and thermal injuries, previous herpetic keratitis, meibomian gland dysfunction, ocular rosacea, diabetes mellitus, Salzmann's nodular degeneration, band keratopathy, previous bacterial ulceration, kerato-conjunctivitis sicca, and epidermolysis bullosa. The conditions that are associated with RCE can be either primary or secondary depending on whether the basement membrane complex abnormality is intrinsic or acquired. Primary types tend to be bilateral, symmetrical and develop in multiple corneal locations. The pathogenetic mechanism of this disorder is related to poor adhesion of the corneal epithelium to the underlying stroma. Excessive matrix metalloproteinase (MMP) activity may play a role in the pathogenesis. Although the majority of patients will respond to simple measures such as padding and antibiotic ointment, RCE resistant to simple measures require approaches that are more elaborate. The common goal of these approaches is to encourage proper formation of adhesion complexes between the epithelium and the stroma. The use of longterm contact lenses, autologous serum eye drops, botulinum toxin, induced ptosis, oral MMP inhibitors, diamond burr polishing of Bowman's membrane have been reported with varying degree of success in treating RCE. Anterior stromal puncture with insulin needles or Neodymium : aluminium-yttriumgarnet may enhance the epithelial adhesion to the basement membrane by scar formation and success rates of up to 80% have been reported in the treatment of recalcitrant RCE. Excimer laser photo-therapeutic keratectomy (PTK) is now a well-established treatment modality for RCE and is being used both safely and effectively. Partial ablation of Bowman's layer with PTK gives a smooth surface for the newly generating epithelium to migrate and form adhesion complexes. The pathogenesis, clinical features, and management options of this common disorder are discussed in this review article.

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Section: Inhibitors Of Mmpmentioning

confidence: 93%

Section: Role Of Mmp Activitymentioning

confidence: 99%

Section: Inhibitors Of Mmpmentioning

confidence: 99%

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Pathogenesis, clinical features and management of recurrent corneal erosions

Ramamurthi

Rahman

Dutton

et al. 2005

Eye

109

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“…MMPs play major physiological roles in degrading and remodeling the ECM. The presence of a clone encoding gelatinase-B (B66) is significant, because MMP-9 has been shown to be expressed in wounded corneal epithelium and is implicated in corneal ulceration and graft rejection (Berman, 1989;Fini et al, 1995Fini et al, , 1996Fini et al, , 1998Barro et al, 1998;Ye and Azar, 1998;Carinato et al, 2000). MMPs have also been implicated in regeneration (Yang and Bryant, 1994;Yang et al, 1997).…”

Section: A Profile Of Gene Expression In Transdifferentiating Cornea mentioning

confidence: 99%

Characterizing gene expression during lens formation in Xenopus laevis: Evaluating the model for embryonic lens induction

Henry

Carinato

Schaefer

et al. 2002

Developmental Dynamics

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Few directed searches have been undertaken to identify the genes involved in vertebrate lens formation. In the frog Xenopus, the larval cornea can undergo a process of transdifferentiation to form a new lens once the original lens is removed. Based on preliminary evidence, we have shown that this process shares many elements of a common molecular/genetic pathway to that involved in embryonic lens development. A subtracted cDNA library, enriched for genes expressed during cornea-lens transdifferentiation, was prepared. The similarities/identities of specific clones isolated from the subtracted cDNA library define an expression profile of cells undergoing cornea-lens transdifferentiation ("lens regeneration") and corneal wound healing (the latter representing a consequence of the surgery required to trigger transdifferentiation). Screens were undertaken to search for genes expressed during both transdifferentiation and embryonic lens development. Significantly, new genes were recovered that are also expressed during embryonic lens development. The expression of these genes, as well as others known to be expressed during embryonic development in Xenopus, can be correlated with different periods of embryonic lens induction and development, in an attempt to define these events in a molecular context. This information is considered in light of our current working model of embryonic lens induction, in which specific tissue properties and phases of induction have been previously defined in an experimental context. Expression data reveal the existence of further levels of complexity in this process and suggests that individual phases of lens induction and specific tissue properties are not strictly characterized or defined by expression of individual genes.

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“…Under physiologic conditions, MMPs activity is tightly controlled, and primary models of regulation include transcriptional control, zymogen activation and dynamic inhibition by tissue inhibitors of metalloproteinases [20]. The metastatic and invasive potential of many cancers also depends on the expression of MMPs and MMP-2 over expression and activity associated with the invasive potential of human tumours [21].…”

Section: Discussionmentioning

confidence: 99%

Effects of cisplatin on matrix metalloproteinase-2 in transformed thyroid cells

Urso

Muscella

Calabriso

et al. 2010

Biochemical Pharmacology

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We investigated the effects of cisplatin (cisPt) on matrix metalloproteinase-2 (MMP-2) gelatinolitic activity in transformed PC E1Araf rat thyroid cells. Cells incubated with increasing cisPt concentrations showed dose-and time-dependent decrease of the MMP-2 protein and activity. CisPt provoked the translocation from the cytosol to the plasma membrane of atypical protein kinase C-zeta (PKC-δ) and the activation of PKB/AKT. The effect of cisPt on MMP-2 was dependent on PKC-δ activation since it was potentiated by a myristoylated PKC-δ pseudo substrate peptide or by PKC-δ down regulation by siRNA. Moreover, MMP-2 activity modulation by cisPt was also dependent on PKB/AKT activation since it was decreased by PKB/AKT down regulation by siRNA or by pharmacological inhibition of PI3K, thus indicating the importance of the balance of PKB/AKT and PKC-δ in regulating the cisPt effect on MMP-2 activity. The PC E1Araf cells displayed a migratory capacity that was blocked by MMP-2 down regulation using siRNA or pharmacological inhibition. The inhibition of cell migration was also obtained with cisPt; in cisPt-treated cells the administration of MMP-2 active protein was able to restore cell migration capacity. In conclusion, the decrease of MMP-2 secretion after cisPt was allowed by PKB/AKT and counteracted by PKC-δ; the cisPt-provoked inhibition of MMP-2 secretion ended in reduction of cell migration.

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Proteolytic mechanisms in corneal ulceration and repair

Cited by 172 publications

References 30 publications

Pathogenesis, clinical features and management of recurrent corneal erosions

Pathogenesis, clinical features and management of recurrent corneal erosions

Characterizing gene expression during lens formation in Xenopus laevis: Evaluating the model for embryonic lens induction

Effects of cisplatin on matrix metalloproteinase-2 in transformed thyroid cells

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