Transdifferentiation of corneal epithelium into epidermis occurs by means of a multistep process triggered by dermal developmental signals

Pearton, David J.; Yang, Ying; Dhouailly, Danielle

doi:10.1073/pnas.0500344102

Cited by 115 publications

(99 citation statements)

References 61 publications

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“…Oxidative stress keeps Pax6 +/-cells in a chronic wound state, which can trigger nuclear exclusion of Pax6 +/-that has been implicated in transdifferentiation of corneal epithelium into non-corneal phenotype. 25 This can also lead to abnormal fibroblast/myofibroblast and myoblast expression, suggesting a new pathway linking reduced Pax6 +/-dosage to aniridia.…”

Section: B Oxidative Stress Wound Healing and Corneal Transparencymentioning

confidence: 99%

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%

Congenital Aniridia and the Ocular Surface

et al. 2016

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“…Such trans-differentiation occurs in a multiple-step process first involving translocation of PAX6 from the corneal epithelial nucleus to the cytoplasm and then its complete repression [70]. Subsequently, some critical signals in the Wnt pathway including β-catenin and Lef-1 are upregulated.…”

Section: Is There Any Evidence Suggesting Niche Regulation Of Limbal mentioning

confidence: 99%

“…Because plasticity leading to de-differentiation and then transdifferentiation into the epidermis can happen even in corneal TACs when engrafted to the embryonic dermis [69,70], one may further speculate that limbal epithelial SCs might be multipotent if an appropriate stromal niche is provided. Such a hypothesis is supported by the findings that neural differentiation of the limbal epithelium takes place when heterotopically transplanted into the mouse hippocampus [125], and that ectodermally derived limbal SCs display neuronal electrophysiology and gradually express the neural SC marker nestin when removed from the limbal niche to an in vitro environment [126].…”

Section: What Signaling Pathways Are Involved In the Niche Control Ofmentioning

confidence: 99%

Niche regulation of corneal epithelial stem cells at the limbus

et al. 2007

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Among all adult somatic stem cells, those of the corneal epithelium are unique in their exclusive location in a defined limbal structure termed Palisades of Vogt. As a result, surgical engraftment of limbal epithelial stem cells with or without ex vivo expansion has long been practiced to restore sights in patients inflicted with limbal stem cell deficiency. Nevertheless, compared to other stem cell examples, relatively little is known about the limbal niche, which is believed to play a pivotal role in regulating self-renewal and fate decision of limbal epithelial stem cells. This review summarizes relevant literature and formulates several key questions to guide future research into better understanding of the pathogenesis of limbal stem cell deficiency and further improvement of the tissue engineering of the corneal epithelium by focusing on the limbal niche.

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“…Corneal cells could be differentiated into hair follicle cells when placed over hair forming embryonic dermis. Differentiation occurred in two steps: corneal cells first dedifferentiated to show limbal basal cell characteristics, then begun to express markers of epidermal differentiation and formed hair follicle-like structures (48)(49)(50). Subpopulations of limbal epithelial cells that acquired nestin positivity under the effect of mitogens in culture differentiated into functional neuronal cells (51,52).…”

Section: Characteristics Of Limbal Epithelial Stem Cellsmentioning

confidence: 99%

“…These cells could be further differentiated along the rod photoreceptor lineage in vitro and in vivo, suggesting that LESC can serve as a source for the treatment of retinal degenerative diseases such as age related macular degeneration or retinitis pigmentosa (53). The molecular basis of these transitions is not understood, although it was supposed that blocking the BMP signaling is important for neuronal differentiation of LESC (52) and the role of the Wnt/b-catenin pathway was suggested in differentiation into hair follicle cells (50,54).…”

Section: Characteristics Of Limbal Epithelial Stem Cellsmentioning

confidence: 99%

Stem cells of the adult cornea: From cytometric markers to therapeutic applications

et al. 2008

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The cornea is a major protective shield of the interior of the eye and represents two thirds of its refractive power. It is made up of three tissue layers that have different developmental origins: the outer, epithelial layer develops from the ectoderm overlying the lens vesicle, whereas the stroma and the endothelium have mesenchymal origin. In the adult organism, the outermost corneal epithelium is the most exposed to environmental damage, and its constant renewal is assured by the epithelial stem cells that reside in the limbus, the circular border of the cornea. Cell turnover in the stromal layer is very slow and the endothelial cells probably do not reproduce in the adult organism. However, recent experimental evidence indicates that stem cells may be found in these layers. Damage to any of the corneal layers leads to loss of transparency and low vision. Corneal limbal stem cell deficiency results in severe ocular surface disease and its treatment by transplantating ex vivo expanded limbal epithelial cells is becoming widely accepted today. Stromal and endothelial stem cells are potential tools of tissue engineering and regenerative therapies of corneal ulcers and endothelial cell loss. In the past few years, intensive research has focused on corneal stem cells aiming to improve the outcomes of the current corneal stem cell transplantation techniques. This review summarizes the current state of knowledge on corneal epithelial, stromal and endothelial stem cells. Special emphasis is placed on the molecular markers that may help to identify these cells, and the recently revealed mechanisms that could maintain their ''stemness'' or drive their differentiation. The techniques for isolating and culturing/ expanding these cells are also described. '

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Transdifferentiation of corneal epithelium into epidermis occurs by means of a multistep process triggered by dermal developmental signals

Cited by 115 publications

References 61 publications

Congenital Aniridia and the Ocular Surface

Congenital Aniridia and the Ocular Surface

Niche regulation of corneal epithelial stem cells at the limbus

Stem cells of the adult cornea: From cytometric markers to therapeutic applications

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