Niche regulation of corneal epithelial stem cells at the limbus

Li, Wei; Hayashida, Yasutaka; Chen, Ying‐Ting; Tseng, Scheffer C.G.

doi:10.1038/sj.cr.7310137

Cited by 257 publications

(219 citation statements)

References 115 publications

(140 reference statements)

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“…The reason for this debilitating condition has been attributed to malfunctioning of the corneal epithelial stem cells visualized by a progressive deterioration of the stem cell environment, the palisades of Vogt [2][3][4][5]. The break-down of the stem cell niche triggers conjunctivalisation and eventually opacification of the cornea [6].…”

Section: Introductionmentioning

confidence: 99%

Analysis of protein composition and protein expression in the tear fluid of patients with congenital aniridia

Ihnatko

Edén

Lagali

et al. 2013

Journal of Proteomics

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Aniridia is a rare congenital genetic disorder caused by haploinsuffiency of the PAX6 gene, the master gene for development of the eye. The expression of tear proteins in aniridia is unknown. To screen for proteins involved in the aniridia pathophysiology, the tear fluid of patients with diagnosed congenital aniridia was examined using two-dimensional electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Two-dimensional map of tear proteins in aniridia has been established and 7 proteins were differentially expressed with P less than 0.01 between aniridia patients and control subjects. Five of them were more abundant in healthy subjects, particularly alpha-enolase, peroxiredoxin 6, cystatin S, gelsolin, apolipoprotein A-1 and two other proteins, zinc-alpha 2-glycoprotein and lactoferrin were more expressed in the tears of aniridia patients. Moreover, immunoblot analysis revealed elevated levels of vascular endothelial growth factor (VEGF) in aniridia tears which is in concordance with clinical finding of pathological blood and lymph vessels in the central and peripheral cornea of aniridia patients. The proteins with different expression in patients tears may be new candidate molecules involved in the pathophysiology of aniridia and thus may be helpful for development of novel treatment strategies for the symptomatic therapy of this vision threatening condition. Biological significance This study is first to demonstrate protein composition and protein expression in aniridic tears and identifies proteins with different abundance in tear fluid from patients with congenital aniridia vs. healthy tears

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Section: Introductionmentioning

confidence: 99%

Analysis of protein composition and protein expression in the tear fluid of patients with congenital aniridia

Ihnatko

Edén

Lagali

et al. 2013

Journal of Proteomics

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“…Corneal epithelial stem cells are regulated by their own microenvironment, including cell-cell and cell-extracellular matrix (ECM), known as the 'stem-cell niche'. [15][16][17] Previous study demonstrated that some growth factors and morphogenetic factors bind directly to particular ECMs and regulate cell proliferation and differentiation. 18 Moreover, the variations in basement membranes are known to depend on the tissue.…”

mentioning

confidence: 99%

Remodeling of epithelial cells and basement membranes in a corneal deficiency model with long-term follow-up

Kameishi

Sugiyama

Yamato

et al. 2015

Laboratory Investigation

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The ocular surface consists of the cornea, conjunctiva, and the limbus that is located in the transitional zone between the cornea and conjunctiva. The corneal epithelial cells are generated through the mitosis of corneal epithelial stem cells in the limbus. This study investigated a rabbit corneal deficiency model prepared by the surgical removal of the corneal and limbal epithelia, which express cytokeratin 12 (K12). After the surgery, K13-expressing conjunctival epithelium migrated onto the corneal surface and completely covered the surface, leading to neovascularization and corneal opacification. However, at 24 and 48 weeks after the surgery, K12-expressing cornea-like cells reappeared on the model ocular surface. These cells formed an island surrounded by invaded conjunctiva and were isolated from the limbus. Interestingly, in the 24-week model surface, a1(IV) and a2(IV) collagen chains, which are normally found in the basement membrane of the native limbus and conjunctiva, and not in the cornea, were continuously deposited throughout the entire basement membrane, including the basement membrane under cornea-like cells. By contrast, in the 48-week model surface, a1(IV) and a2(IV) collagen chains were absent from the basement membrane beneath the central part of cornea-like cells and were localized below the invaded conjunctiva and the transitional zone between cornea-like cells and the invaded conjunctiva, which had similar distribution to the native ocular basement membrane. Moreover, K12, K14, p63, vimentin, and a1(IV) and a2(IV) collagen chains, which are colocalized in the native limbus, were all present at the transitional zone of the 48-week model surface. Therefore, a limbus-like structure appeared to be reconstructed on the surface of the 48-week model as a stem cell niche. This study should aid in the understanding of human corneal deficiency, the correlation between the epithelial cell phenotype and the composition of the basement membrane, and the epithelial stem cell niche.

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“…Chronic inflammation in the limbus, the common denominator of limbal stem cell deficiency, had been confirmed to threaten the well-being of transplanted limbal autograft. [24][25][26] Long-term ICs infiltration in the limbus may result in loss of LSCs and dysfunction of remaining LSCs, then leads to delay of corneal epithelial recovery. In eyes classified as grade I and II injury, DCs infiltration in the limbus was found.…”

Section: Eyementioning

confidence: 99%

In vivo confocal microscopy of early corneal epithelial recovery in patients with chemical injury

Xiang

et al. 2015

Eye

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Purpose To investigate the early recovery of corneal epithelium in patients with chemical injuries by the application of in vivo laser scanning confocal microscopy (LSCM). Methods LSCM was performed on 26 eyes of 18 consecutive patients at 1, 2, and 3 months post injury. The morphology of central corneal epithelium and limbus was evaluated. Analysis was performed to compare the densities of corneal apical surface cells (ASCs) and basal epithelial cells (BECs) among different injury severity and time points after injury. The comparisons were also made on inflammatory cells (ICs) and dendritic cells (DCs) infiltrating at the limbus. Moreover, the presence rate of palisades of Vogt (POV) was analyzed at 3 months post injury. Results Corneal re-epithelialization was found within 3 months post injury in all eyes, except that persistent epithelium defect was identified in grade IV injured eyes even at 3 months after injury. The injury severity had a significantly negative correlation with the densities of ASCs. However, it had no relationship with the densities of BECs. The density of ICs at the limbus decreased significantly with the prolongation of follow-up, except in the grade I injured eyes. The presence rate of POV also had a significantly negative correlation with injury severity.Conclusion Epithelial recovery after chemical injury varied in cellular morphology and the densities of ASCs among eyes with different injury severity. The presence rates of POV decreased with the aggravation of injury. LSCM is a feasible method for observing the early recovery of corneal epithelium in patients with chemical injuries.

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Niche regulation of corneal epithelial stem cells at the limbus

Cited by 257 publications

References 115 publications

Analysis of protein composition and protein expression in the tear fluid of patients with congenital aniridia

Analysis of protein composition and protein expression in the tear fluid of patients with congenital aniridia

Remodeling of epithelial cells and basement membranes in a corneal deficiency model with long-term follow-up

In vivo confocal microscopy of early corneal epithelial recovery in patients with chemical injury

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