Corneal development associated with eyelid opening

Zieske, James D.

doi:10.1387/ijdb.041860jz

Cited by 150 publications

(127 citation statements)

References 44 publications

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“…11 Such a gross structural failure is, in turn, frequently associated with abnormalities of the globe, as defective eyelid closure results in an abnormal environment on the surface of the developing eye. 12 Conversely, colobomas arising during the later phases of eyelid development are typically much smaller, and, owing to a period of lid closure, the development of the underlying eye and ocular surface also tends to be normal.…”

Section: Eyelid Embryologymentioning

confidence: 99%

The incidence, embryology, and oculofacial abnormalities associated with eyelid colobomas

Smith

Verity

Collin

2015

Eye

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Purpose To describe a cohort of patients with congenital eyelid coloboma, to identify associated ocular and craniofacial abnormalities, and to establish any correlation between the size and location of eyelid colobomas and the presence of such abnormalities. Methods An observational case series of 55 patients with eyelid coloboma treated by a single surgeon (JROC) between 1985 and 2005. Results Eyelid colobomas predominantly affected the upper lids (93%), and were typically unilateral (76%). About a third (29%) were an isolated finding, with the remainder associated with other ocular (62%) and/or craniofacial (53%) abnormalities. Of those with ocular abnormalities; 19 (56%) had conjunctival traction bands, 16 (47%) choristomas, and 8 (24%) an abnormal globe. Of those with craniofacial abnormalities; 13 (45%) had Goldenhar Syndrome, 10 (35%) clefting disorders, and 4 (14%) Fraser Syndrome. Clefting disorders were typically associated with more severe colobomas and a higher incidence of conjunctival traction bands, first arch syndromes with smaller colobomas and more choristomas. Overall large colobomas were significantly associated with the presence of other craniofacial defects compared with small colobomas (Po0.01, w 2 ), but coloboma size did not correspond with the presence of other ocular abnormalities. Conclusions Coloboma size, location, and associations in this series are consistent with our current understanding of eyelid embryogenesis. It is likely that those colobomas associated with other craniofacial and ocular abnormalities are those which result from errors earlier in embryogenesis during eyelid specification, growth, and closure, whereas isolated colobomas arise later during eyelid separation, and after codependent structures have developed.

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Section: Eyelid Embryologymentioning

confidence: 99%

The incidence, embryology, and oculofacial abnormalities associated with eyelid colobomas

Smith

Verity

Collin

2015

Eye

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“…Between birth and eyelid opening, the number of proliferating keratocytes in the developing corneal stroma decreases dramatically from 20% of the total to nearly zero (Zieske, 2004). At the time of eyelid opening, keratocytes have withdrawn from the cell cycle, remaining in G0 rather than undergoing complete terminal differentiation (Zieske, 2004).…”

Section: Keratocyte Origin and Plasticitymentioning

confidence: 99%

The keratocyte: Corneal stromal cell with variable repair phenotypes

West‐Mays

Dwivedi

2006

The International Journal of Biochemistry & Cell Biology

320

223

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Keratocytes, also known as fibroblasts, are mesencyhmal-derived cells of the corneal stroma. These cells are normally quiescent, but they can readily respond and transition into repair phenotypes following injury. Cytokines and other growth factors that provide autocrine signals for stimulating wound responses in resident cells are typically presented by platelets at the site of an injury. However, due to the avascular nature of the cornea many of the environmental cues are derived from the overlying epithelium. Corneal epithelial-keratocyte cell interactions have thus been extensively studied in numerous in vivo corneal wound healing settings, as well as in in vitro culture models. Exposure to the different epithelial-derived factors, as well as the integrity of the epithelial substratum, are factors known to impact the keratocyte response and determine whether corneal repair will be regenerative or fibrotic in nature. Finally, the recent identification of bone-marrow derived stem cells in the corneal stroma suggests a further complexity in the regulation of the keratocyte phenotype following injury. KeywordsKeratocyte; Cornea; Injury; Apoptosis; Myofibroblasts; Transparency; Plasticity Cell facts• Keratocytes are neural-crest derived mesenchymal cells that sparsely populate the corneal stroma.• Keratocytes are quiescent, dendritic cells that upon injury to the cornea are stimulated to either undergo apoptosis or transition into repair phenotypes.• Structural integrity of the basement membrane is critical for minimizing the fibrotic response of keratocytes and subsequent scarring and loss of corneal clarity.• Bone-marrow derived stem cells have been detected in the corneal stroma and may participate in the activation of the keratocytes following injury.

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“…It is a transparent tissue located on the anterior ocular surface and consists of a stratified non-keratinized epithelium, a thick stroma scattered with keratocytes and a single-cell-layer endothelium (Zieske, 2004). The outermost cell layers of the corneal epithelium serve as a protective barrier against fluid loss and pathogen penetration.…”

Section: Introductionmentioning

confidence: 99%

Wnt/β-catenin signaling modulates corneal epithelium stratification via inhibition of Bmp4 during mouse development

et al. 2015

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The development of organs with an epithelial parenchyma relies on reciprocal mesenchymal-epithelial communication. Mouse corneal epithelium stratification is the consequence of a coordinated developmental process based on mesenchymal-epithelial interactions. The molecular mechanism underlying these interactions remains unclear. The Wnt/β-catenin signaling pathway is involved in fundamental aspects of development through the regulation of various growth factors. Here, we show that conditional ablation of either β-catenin (Ctnnb1 cKO ) or co-receptors Lrp5/6 (Lrp5/6 cKO ) in corneal stromal cells results in precocious stratification of the corneal epithelium. By contrast, ectopic expression of a murine Ctnnb1 gainof-function mutant (Ctnnb1 cGOF ) retards corneal epithelium stratification. We also discovered that Bmp4 is upregulated in the absence of β-catenin in keratocytes, which further triggers ERK1/2 (Mapk3/1) and Smad1/5 phosphorylation and enhances transcription factor p63 (Trp63) expression in mouse corneal basal epithelial cells and in a human corneal epithelial cell line (HTCE). Interestingly, mouse neonates given a subconjunctival BMP4 injection displayed a phenotype resembling that of Ctnnb1 cKO . Conditional ablation of Bmp4 eradicates the phenotype produced in Ctnnb1 cKO mice. Furthermore, ChIP and promoter-luciferase assays show that β-catenin binds to and suppresses Bmp4 promoter activity. These data support the concept that cross-talk between the Wnt/β-catenin/ Bmp4 axis (in the stromal mesenchyme) and Bmp4/p63 signaling (in the epithelium) plays a pivotal role in epithelial stratification during corneal morphogenesis.

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Corneal development associated with eyelid opening

Cited by 150 publications

References 44 publications

The incidence, embryology, and oculofacial abnormalities associated with eyelid colobomas

The incidence, embryology, and oculofacial abnormalities associated with eyelid colobomas

The keratocyte: Corneal stromal cell with variable repair phenotypes

Wnt/β-catenin signaling modulates corneal epithelium stratification via inhibition of Bmp4 during mouse development

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