Pathogenesis of Ulcers of the Alkali-Burned Cornea

Brown, Stuart I.; Weller, Carol; Akiya, Shinobu

doi:10.1001/archopht.1970.00990030207014

Cited by 65 publications

(25 citation statements)

References 7 publications

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“…In the burned cornea, neutrophil infiltration is particularly important, and it is an early event. If uncontrolled, the release of various proteases by neutrophils can result in stromal degradation and ulceration, eventually leading to permanent vision-impairing corneal opacification and neovascularization (31). The present study showed that intraocular TSG-6 decreased the infiltration of neutrophils into the cornea and the production of proteases following injury.…”

Section: Fig 4 Microarray Analysis Of the Cornea Following Injury supporting

confidence: 51%

Anti-inflammatory protein TSG-6 reduces inflammatory damage to the cornea following chemical and mechanical injury

Roddy²,

Choi³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

207

193

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Previous reports demonstrated that adult stem/progenitor cells from bone marrow (multipotent mesenchymal stem cells; MSCs) can repair injured tissues with little evidence of engraftment or differentiation. In exploring this phenomenon, our group has recently discovered that the therapeutic benefits of MSCs are in part explained by the cells being activated by signals from injured tissues to express an anti-inflammatory protein TNF-α-stimulated gene/protein 6 (TSG-6). Therefore, we elected to test the hypothesis that TSG-6 would have therapeutic effects in inflammatory but noninfectious diseases of the corneal surface. We produced a chemical and mechanical injury of the cornea in rats by brief application of 100% ethanol followed by mechanical debridement of corneal and limbal epithelium. Recombinant human TSG-6 or PBS solution was then injected into the anterior chamber of the eye. TSG-6 markedly decreased corneal opacity, neovascularization, and neutrophil infiltration. The levels of proinflammatory cytokines, chemokines, and matrix metalloproteinases were also decreased. The data indicated that TSG-6, a therapeutic protein produced by MSCs in response to injury signals, can protect the corneal surface from the excessive inflammatory response following injury.inflammation | TNF-α-stimulated protein 6 | mesenchymal stem cells | neutrophil | matrix metalloproteinase

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Section: Fig 4 Microarray Analysis Of the Cornea Following Injury supporting

confidence: 51%

Anti-inflammatory protein TSG-6 reduces inflammatory damage to the cornea following chemical and mechanical injury

Roddy²,

Choi³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

207

193

View full text Add to dashboard Cite

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“…Therefore, a powerful chemokine is needed to attract neutrophils to the cornea, such as IL-8, which is known to be able to attract neutrophils into inflamed tissues (Baggiolini et al, 1994). On the other hand, neutrophil infiltration in an injured cornea needs to be tightly controlled; otherwise, the release of various proteases by neutrophils may result in stromal degradation and ulceration, which in turn might lead to corneal opacity and neovascularization (Brown et al, 1970), causing decreased vision or even blindness. SP has been reported to chemoattract rabbit neutrophils (Marasco et al, 1981), activate human neutrophils (Serra et al, 1988), and increase neutrophil adhesion to bovine bronchial epithelial cells (DeRose et al, 1994); however, our results show that SP is not able to attract human neutrophils directly but that it does so by stimulating keratocytes to produce IL-8, which then attracts neutrophils.…”

Section: Substance P Enhances Keratocyte Migrationmentioning

confidence: 99%

Substance P Enhances Keratocyte Migration and Neutrophil Recruitment through Interleukin-8

et al. 2015

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Keratocytes, the resident cells of the corneal stroma, are responsible for maintaining turnover of this tissue by synthesizing extracellular matrix components. When the cornea is injured, the keratocytes migrate to the wounded site and participate in the stromal wound healing. The neuropeptide substance P (SP), which is also known to be produced by non-neuronal cells, has previously been implicated in epithelial wound healing after corneal injury. Corneal scarring, which occurs in the stroma when the process of wound healing has malfunctioned, is one of the major causes of preventable blindness. This study aimed to elucidate the potential role of SP in keratocyte migration and therefore in stromal wound healing. We report that the expression and secretion of SP in human keratocytes are increased in response to injury in vitro. Moreover, SP enhances the migration of keratocytes by inducing the actin cytoskeleton reorganization and focal adhesion formation through the activation of the phosphatidylinositide 3-kinase and Ras-related C3 botulinum toxin substrate 1/Ras homolog gene family, member A pathway. Furthermore, SP stimulation leads to upregulated expression of the proinflammatory and chemotactic cytokine interleukin-8 (IL-8), which also contributes significantly to SP-enhanced keratocyte migration and is able to attract neutrophils. In addition, the preferred SP receptor, the neurokinin-1 receptor, is necessary to induce keratocyte migration and IL-8 secretion.In conclusion, we describe new mechanisms by which SP enhances migration of keratocytes and recruits neutrophils, two necessary steps in the corneal wound-healing process, which are also likely to occur in other tissue injuries.

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“…No coliagenolytic activity can be found present in the normal human cornea [Brown and W eller, 1970a;Slansky et al, 1969a] or in parenchy mal corneal dystrophy or healed keratitis (interstitial keratitis, disciform keratitis).…”

Section: Collagenase In the Human Corneamentioning

confidence: 97%

“…etal., 1969 b] and of the human corneal epithelium [Itoi ero/., 1969a;Brown and W eller, 1970a], However, the collagenase of the post-pregnancy uterus of the rat is not inhibited by cysteine [Jeffrey and G ross, 1967] and that of the synovial fluid of rheumatoid arthritis is not inhibited by serum [Evanson el al., 1967],…”

Section: Collagenase Inhibitorsmentioning

confidence: 99%

Collagenase and the Collagenase Inhibitors in Torpid Ulcers of the Cornea

François¹,

Cambie²

1972

Ophthalmic Res

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Rabbit corneas were burned with 0.5% caustic soda. Subsequently, they were treated with a solution of cysteine 0.15m or a suspension of cystine 0.15 m, with excellent results. Clinically, we obtained surprisingly good results by treating torpid ulcers of the cornea with a suspension of cystine 0.15 m. In the case of infected ulcers of the cornea which could not be sterilized, this treatment was without effect.

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Pathogenesis of Ulcers of the Alkali-Burned Cornea

Cited by 65 publications

References 7 publications

Anti-inflammatory protein TSG-6 reduces inflammatory damage to the cornea following chemical and mechanical injury

Anti-inflammatory protein TSG-6 reduces inflammatory damage to the cornea following chemical and mechanical injury

Substance P Enhances Keratocyte Migration and Neutrophil Recruitment through Interleukin-8

Collagenase and the Collagenase Inhibitors in Torpid Ulcers of the Cornea

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