Increased Apoptosis and Abnormal Wound-Healing Responses in the Heterozygous<i>Pax6</i><sup>+/−</sup>Mouse Cornea

Ramaesh, Thaya; Ramaesh, Kanna; Leask, Rosemary; Springbett, Anthea; Riley, Simon C.; Dhillon, Baljean; West, John D.

doi:10.1167/iovs.05-1028

Cited by 47 publications

(57 citation statements)

References 39 publications

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“…8,10 In experiments with Pax6 +/-mice, several insights have been gained into impaired corneal wound healing. 16,20 One important finding was that increased stromal apoptosis occurred after wounding, and it has been suggested that apoptosis, as well as deficient and delayed extracellular matrix metabolism, aggravated the corneal changes. 16 A summary of the corneal wound healing and stromal response in AAK is given in Table 1.…”

Section: B Oxidative Stress Wound Healing and Corneal Transparencymentioning

confidence: 99%

“…Increased oxidative stress present in AAK may lead to a greater extent of apoptosis in the corneal epithelium and abnormal corneal wound healing. 16 In these processes, peroxiredoxin 6, VEGF, gelsolin, apolipoprotein A-1, and zinc-α2 glycoprotein may play a substantial role. One study found elevated levels of dinucleotides Ap4A and Ap5A in aniridic tears.…”

Section: The Tear Filmmentioning

confidence: 99%

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Congenital Aniridia and the Ocular Surface

et al. 2016

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Aniridia is a congenital pan-ocular disorder caused by haplo-insufficiency of Pax6, a crucial gene for proper development of the eye. Aniridia affects a range of eye structures, including the cornea, iris, anterior chamber angle, lens, and fovea. The ocular surface in particular can be severely affected by a progressive pathology termed aniridiaassociated keratopathy (AAK), markedly contributing to impaired vision. The purpose of this review is to provide an update of the current knowledge of the genetic, clinical, micromorphological, and molecular aspects of AAK. We draw upon material presented in the literature and from our own observations in large aniridia cohorts. We summarize signs and symptoms of AAK, describe current options for management, and discuss the latest research 2 findings that may lead to better diagnosis and new treatment or prevention strategies for this debilitating ocular surface condition.

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Section: B Oxidative Stress Wound Healing and Corneal Transparencymentioning

confidence: 99%

Section: The Tear Filmmentioning

confidence: 99%

Congenital Aniridia and the Ocular Surface

et al. 2016

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“…A volume of 3 ml of conditioned media from each sample was diluted 1 : 1 with deionised water, mixed with 6 ml of sample application buffer, and subjected to gelatin zymography as described by Ramaesh et al 14 For quantitative analysis, the gelatin zymograms were produced by loading further diluted conditioned media, containing only 1 ml of each sample. This was done to produce a clear non-overlapping band for each sample.…”

Section: Gelatin Zymography and Reverse Zymographymentioning

confidence: 99%

Effects of N-acetylcysteine on matrix metalloproteinase-9 secretion and cell migration of human corneal epithelial cells

Ramaesh

Riley

et al. 2012

Eye

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Background Matrix metalloproteinase-9 (MMP-9) secreted by corneal epithelial cells has a role in the remodelling of extracellular matrix and migration of epithelial cells. Elevated levels of MMP-9 activity in the ocular surface may be involved in the pathogenesis of corneal diseases. N-acetylcysteine (NAC) has been used to treat corneal diseases, including recurrent epithelial erosions. In this study, its effects on the MMP-9 secretion and human corneal epithelial (HCE) cell migration were evaluated in vitro. Methods Confluent HCE cell cultures were treated with 0-20 mM NAC, and tested for MMP-9 secretion and epithelial cell migration by gelatin zymography and scratch wound assay, respectively. Comparisons between different treatment groups were made using analysis of variance, followed by multiple pairwise comparisons. Results Twenty mM NAC inhibited the secretion of MMP-9 significantly. Cell migration, assessed after 24 h of wounding, showed a highly significant dose-dependent inhibitory effect. Conclusions This study shows that NAC reduces MMP-9 production by HCE cells and inhibits cell migration in vitro. This information helps to elucidate the mechanisms by which NAC may be beneficial therapeutically and suggests that NAC may be useful for managing corneal erosions and related conditions.

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“…Apoptotic keratocytes may, however, be noted away from sites of epithelial injury in keratoconus corneas (Kim, et al, 1999), leading to the hypothesis that abnormally high levels of ongoing keratocyte apoptosis could play a role in the pathophysiology of this ectatic corneal disease (Kim, et al, 1999;Chwa, et al, 2006). Abnormally high levels of keratocyte apoptosis have also been associated with the pathophysiology of aniridia (Ramaesh, et al, 2006). Thus, it appears that stromal apoptosis is tightly controlled during homeostasis in the absence of corneal injury or disease.…”

Section: Introductionmentioning

confidence: 99%

Apoptosis in the initiation, modulation and termination of the corneal wound healing response

Wilson

Chaurasia

Medeiros

2007

Experimental Eye Research

134

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Stromal keratocyte apoptosis has been well-characterized as an early initiating event of the corneal wound healing response, triggering subsequent cellular processes that include bone marrow-derived cell infiltration, proliferation and migration of residual keratocyte cells, and, in some circumstances, generation of myofibroblast cells. Recent studies, however, have suggested a more general role for apoptosis in the overall stromal wound healing response that includes modulation and termination functions. This review article highlights, and ties together, recent studies that have demonstrated the important role apoptosis likely plays in the weeks to months following an initial insult to the cornea -depending on the type and extent of corneal injury.

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Increased Apoptosis and Abnormal Wound-Healing Responses in the HeterozygousPax6^+/−Mouse Cornea

Cited by 47 publications

References 39 publications

Congenital Aniridia and the Ocular Surface

Congenital Aniridia and the Ocular Surface

Effects of N-acetylcysteine on matrix metalloproteinase-9 secretion and cell migration of human corneal epithelial cells

Apoptosis in the initiation, modulation and termination of the corneal wound healing response

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Increased Apoptosis and Abnormal Wound-Healing Responses in the HeterozygousPax6+/−Mouse Cornea

Cited by 47 publications

References 39 publications

Congenital Aniridia and the Ocular Surface

Congenital Aniridia and the Ocular Surface

Effects of N-acetylcysteine on matrix metalloproteinase-9 secretion and cell migration of human corneal epithelial cells

Apoptosis in the initiation, modulation and termination of the corneal wound healing response

Contact Info

Product

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Increased Apoptosis and Abnormal Wound-Healing Responses in the HeterozygousPax6^+/−Mouse Cornea