Effect of Metalloprotease Inhibitors on Corneal Allograft Survival

Stuart, Patrick M.; Fan, Ping; Yin, Xuewei; Hašková, Zdenka; Plambeck, Stacey; Ferguson, T.

doi:10.1167/iovs.03-0932

Cited by 22 publications

(17 citation statements)

References 37 publications

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“…MMP-2, together with MMP-9, degrades basement membrane components such as collagen IV, and is now extensively studied in the eye tissue (Sivak and Fini, 2002). Through numerous studies of MMP-2 and MMP-9, many investigators have shown that in corneal lesions such as keratitis (Yang et al, 2003;Xue et al, 2003), corneal alkali burn (Zhang et al, 2002;Barros et al, 2007), and corneal transplant rejection (Stuart et al, 2004), the expression levels and activities of MMP-2 and MMP-9 are increased, and they are considered the main factors contributing to these pathologies.…”

Section: Discussionmentioning

confidence: 99%

Activity of matrix metalloproteinases 2 and 9 in cultured rabbit corneal epithelium cells stimulated by tumor necrosis factor alpha

et al. 2015

Genet. Mol. Res.

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ABSTRACT. We studied the activity of matrix metalloproteinases (MMP) 2 and 9 generated by cultured rabbit corneal epithelium cells that had been stimulated with tumor necrosis factor alpha (TNF-a), to investigate the possible regulative mechanisms of MMP-2/9 and their potential effect on corneal inflammatory diseases. The rabbit corneal epithelium cells were cultured in vitro and incubated with different concentrations of TNF-a (0, 1, 10, and 100 ng/mL) for 24 h. The activity of MMP-2/9 was examined using gelatin zymography. The results were analyzed by computer image analysis and statistical tests. TNF-a stimulated the secretion of MMP-2/9 in a dose-dependent manner, and MMP-2 was activated by TNF-a. Inflammatory factors such as TNF-a can stimulate MMP-2/9 activity in corneal epithelium cells. This may be a potential manipulating mechanism of MMP expression in the 6361 MMP-2/9 in TNF-α-stimulated rabbit corneal epithelium cells ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (2): 6360-6368 (2015) pathogenesis of corneal diseases, and could play an important role in the prevention and treatment of corneal inflammatory diseases.

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Section: Discussionmentioning

confidence: 99%

Activity of matrix metalloproteinases 2 and 9 in cultured rabbit corneal epithelium cells stimulated by tumor necrosis factor alpha

et al. 2015

Genet. Mol. Res.

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“…Therefore, the concentration of a1-antitrypsin in aqueous humour cannot be used as a prognostic indicator at the time of corneal rejection. Interestingly, it has been suggested that certain metalloproteinase activity is equal to serine proteinase activity (Ando et al 1993), and it has been shown that metalloproteinase inhibitor treatment prolongs corneal allograft survival and results in a modest increase in corneal allograft acceptance in a mouse model (Stuart et al 2004). In perspective, our findings could lead to a new treatment of corneal rejection with local use of a1-antitrypsin augmentation therapy in the anterior chamber.…”

Section: Discussionmentioning

confidence: 59%

Alpha‐1‐‐antitrypsin in aqueous humour from patients with corneal allograft rejection

Funding

Vorum

Nexø

et al. 2005

Acta Ophthalmologica Scandinavica

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ABSTRACT.Purpose: To investigate the presence and concentration of a1-antitrypsin in aqueous humour at the time of corneal rejection and to compare results obtained from patients with reversible and irreversible rejection. Methods: Samples of aqueous humour were obtained from 17 patients with acute corneal endothelial allograft rejection. The presence of a1-antitrypsin in aqueous humour was confirmed by immunoblotting and measured employing a sandwich ELISA. Total protein concentrations in aqueous humour were measured using Bradford's method. The outcome of corneal rejection episodes was determined 1 month after diagnosing corneal rejection and described as reversible or irreversible rejection. Results: a1-antitrypsin was detected in aqueous humour. Patients with reversible rejection had significantly higher a1-antitrypsin concentration than patients with irreversible rejection (p = 0.044). There was no significant difference in total protein concentrations (p = 0.745), and no correlation was found between a1-antitrypsin and total protein concentrations (p = 0.368). Conclusions: a1-antitrypsin in aqueous humour seems to signal a favourable outcome of corneal rejection. The possible mechanism is discussed.

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“…Penetrating keratoplasties were performed with minor modification from previously published methods 21 . In summary, Provisc (Alcon Laboratories, Fort Worth, TX) was injected into the anterior chamber of the eye of an anesthetized donor.…”

Section: Methodsmentioning

confidence: 99%

Feasibility Study of Lamellar Keratoplasty in a Murine Model

Huang

Planck

Lee

2009

Ocular Immunology and Inflammation

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Purpose-In contrast to penetrating keratoplasty (PK), the donor cornea in lamellar keratoplasty (LK) remains separated from the host aqueous humor. There is debate about relative merits of each approach, but experimental comparisons have never been performed in animal models. Therefore, we developed a murine LK model.Methods-For allogeneic PK and LK surgeries, corneas of C57BL/6 mice were transplanted to BALB/c mice, assessed by slit lamp, and scored for opacity, edema, and neovascularization up to 46 d post-transplantation. Additional PK or LK surgeries were performed for histological assessment.Results-Graft rejection rate was significantly less in LK vs. PK (69.2% vs. 100%), as was neovascularization (84.6% vs. 100%). In LK, inflammatory cells infiltrated primarily the button; in PK, heavier infiltration was observed throughout the cornea.Conclusions-We demonstrate the feasibility of LK in mice and present data suggesting that the inflammatory response in LK differs from that in PK.

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Effect of Metalloprotease Inhibitors on Corneal Allograft Survival

Abstract: MMP inhibitor treatment of cornea-derived endothelial cells results in increased FasL expression and function. MMP inhibitor treatment prolongs corneal allograft survival and results in a modest increase in corneal allograft acceptance.

Cited by 22 publications

References 37 publications

Activity of matrix metalloproteinases 2 and 9 in cultured rabbit corneal epithelium cells stimulated by tumor necrosis factor alpha

Activity of matrix metalloproteinases 2 and 9 in cultured rabbit corneal epithelium cells stimulated by tumor necrosis factor alpha

Alpha‐1‐‐antitrypsin in aqueous humour from patients with corneal allograft rejection

Feasibility Study of Lamellar Keratoplasty in a Murine Model

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