Self-organized centripetal movement of corneal epithelium in the absence of external cues

Lobo, Erwin P.; Delic, Naomi C.; Richardson, Alex; Raviraj, Vanisri; Halliday, Gary M.; Girolamo, Nick Di; Myerscough, Mary R.; Lyons, J. Guy

doi:10.1038/ncomms12388

Cited by 45 publications

(90 citation statements)

References 28 publications

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“…c,d) . Mathematical modeling of this process has demonstrated that the development of this pattern requires no external cues; rather, it is purely population pressure‐driven . Lineage tracing experiments using a mosaic mouse model have recently shown that a single precursor cell is responsible for a unique spoke that forms, confirming the role of stem cells in the maintenance of the corneal epithelium .…”

Section: The Corneamentioning

confidence: 87%

“…In vivo studies combined with mathematical modeling have described a striking spoke‐like pattern that forms as corneal epithelia migrate from the limbus, moving centripetally toward the apex of the cornea (Fig. c,d) . Mathematical modeling of this process has demonstrated that the development of this pattern requires no external cues; rather, it is purely population pressure‐driven .…”

Section: The Corneamentioning

confidence: 99%

“…Schematic of the human eye (a) the limbus is a narrow area, located at the periphery of the cornea, where the stem cells reside; (b) cellular structure of the cornea, depicting the five distinct layers and the depth of penetration of each ultraviolet ( UV ) wavelength; (c) colored arrows depict the direction that the epithelial progeny move from the limbus into the epithelium; (d) A K14Cre ER T 2 ‐Confetti murine eye, 50‐week post‐tamoxifen injection with fluorescently labeled corneal epithelial cells, derived from stem cells in the limbus. The bright halo in the center is autofluorescence of the crystalline lens.…”

Section: The Corneamentioning

confidence: 99%

“…Using computer modeling, Lobo and colleagues recently demonstrated that the well‐documented spoke pattern that corneal epithelial cell clones form as they move from the limbus requires no external physiological cues. Rather, this pattern can be simply explained by population pressure from the periphery.…”

Section: Cellular Changes In Response To Uv Irradiationmentioning

confidence: 99%

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Damaging Effects of Ultraviolet Radiation on the Cornea

Delic

Lyons

Girolamo

et al. 2017

Photochem & Photobiology

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The cornea sits at the anterior aspect of the eye and, like the skin, is highly exposed to ultraviolet radiation (UVR). The cornea blocks a significant proportion of UVB from reaching the posterior structures of the eye. However, UVA can penetrate the full thickness of the cornea, even reaching the anterior portion of the lens. Epidemiological data indicate that UVR is a contributing factor for a multitude of diseases of the cornea including pterygium, photokeratitis, climatic droplet keratopathy and ocular surface squamous neoplasia (OSSN), although the pathogenic mechanisms of each require further elucidation. UVR is a well‐known genotoxic agent, and its effects have been well characterized in organs such as the skin. However, we are only beginning to identify its effects on the cornea, such as the UVR signature C → T and CC → TT transversions identified by sequencing and increased proliferative and shedding rates in response to UVR exposure. Alarmingly, a single low‐dose exposure of UVR to the cornea is sufficient to elicit genetic, molecular and cellular changes, supporting the consideration of using protective measures, such as wearing sunglasses when outdoors. The aim of this review was to describe the adverse effects of UVR on the cornea.

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Section: The Corneamentioning

confidence: 87%

Section: The Corneamentioning

confidence: 99%

Section: The Corneamentioning

confidence: 99%

Section: Cellular Changes In Response To Uv Irradiationmentioning

confidence: 99%

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Damaging Effects of Ultraviolet Radiation on the Cornea

Delic

Lyons

Girolamo

et al. 2017

Photochem & Photobiology

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“…The basal epithelial TACs then proliferate, differentiate and migrate anteriorly toward the corneal surface, finally differentiating to terminal differentiated cells (TDC) that undergo desquamation and shedding (Fig. 1A) [4••, 10••, 14]. …”

Section: Corneal Epithelial Homeostasis: the Classic And The Current mentioning

confidence: 99%

Limbal and corneal epithelial homeostasis

Yazdanpanah

Jabbehdari²,

Djalilian

2017

Current Opinion in Ophthalmology

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Purpose of Review The aim of this review is to describe the underlying mechanisms of corneal epithelial homeostasis in addition to illustrating the vital role of the limbal epithelial stem cells (LESCs) and the limbal niche in epithelial regeneration and wound healing. Recent Findings The shedded corneal epithelial cells are constantly replenished by the LESCs which give rise to epithelial cells that proliferate, differentiate and migrate centripetally. While some recent studies have proposed that epithelial stem cells may also be present in the central cornea, the predominant location for the stem cells is the limbus. The limbal niche is the specialized micro-environment consisting of cells, extra-cellular matrix and signaling molecules that are essential for the function of LESCs. Disturbances to limbal niche can result in LESC dysfunction, therefore, limbal stem cell deficiency should also be considered a limbal niche deficiency. Current and in–development therapeutic strategies are aimed at restoring the limbal niche, by medical and/or surgical treatments, administration of trophic factors and cell based therapies. Summary The corneal epithelium is constantly replenished by LESCs that are housed within the limbal niche. The limbal niche is the primary determinant of the LESC function and novel therapeutic approaches should be focused on regeneration of this microenvironment.

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A Bioengineering‐Regenerative Medicine Approach for Ocular Surface Reconstruction Using a Functionalized Native Cornea‐Derived Bio‐Scaffold

Park,

Richardson,

Delic

et al. 2023

Adv Funct Materials

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Limbal stem cell deficiency (LSCD) is characterized by the loss of limbal epithelial stem cells (LESCs) which compromises corneal transparency, leading to blindness. It cannot be treated with pharmacological or corneal transplantation interventions, instead a specialized stem cell (SC) therapy is needed to restore eye health and sight. Herein, a native cornea‐derived biomaterial, a by‐product of a laser refractive surgical procedure called small incision lenticule extraction is identified as a new cell delivery matrix. Culture conditions are optimized to facilitate LESC attachment, expansion and stratification, and their identity is immunophenotyped. Using electron microscopy, bio‐constructs display stratification, similar to the architectural and cellular organization of a native mammalian cornea with formation of a basement membrane and an orderly array of collagen fibrils. Neuronal growth and depleted CD45+/CD14+ leukocytes on lenticules are also shown, suggesting that in transplantation experiments, they will re‐innervate and not trigger a host‐mediated immune response. Finally, human lenticules are geometrically customized to successfully fit them over a LSCD murine cornea ex vivo, during which they maintain curvature. The authors are poised to conduced similar studies in live mice using these and other carriers currently used in the clinic to compare SC therapy outcomes.

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Self-organized centripetal movement of corneal epithelium in the absence of external cues

Cited by 45 publications

References 28 publications

Damaging Effects of Ultraviolet Radiation on the Cornea

Damaging Effects of Ultraviolet Radiation on the Cornea

Limbal and corneal epithelial homeostasis

A Bioengineering‐Regenerative Medicine Approach for Ocular Surface Reconstruction Using a Functionalized Native Cornea‐Derived Bio‐Scaffold

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