Corneal Development, Limbal Stem Cell Function, and Corneal Epithelial Cell Migration in the<i>Pax6</i><sup>+/−</sup>Mouse

Collinson, J. Martin; Chanas, Simon A.; Hill, Robert E.; West, John D.

doi:10.1167/iovs.03-1118

Cited by 139 publications

(146 citation statements)

References 34 publications

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“…The defective healing is observed both in mice models and clinically, and is related to abnormalities in the cell surface glycoconjugate and deficient and delayed extracellular matrix metabolism. 1,7,10,20,22,23 The volume of oxidized proteins increases with age in normal corneas but is more extensive in Pax6 +/-. Corneal epithelia, both superficial and basal cells in Pax6 +/-mice, have demonstrated more severe oxidative modifications.…”

Section: B Oxidative Stress Wound Healing and Corneal Transparencymentioning

confidence: 99%

“…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%

“…The PAX6 genetic defect influences the regulation of the stem cells, leading to a breakdown of normal function of the limbal barrier and causing conjunctiva to invade the corneal surface. 20,31 The limbus area acts as a junctional barrier to separate the cornea and conjunctiva, and there is no evidence that conjunctival epithelial cells can transdifferentiate into corneal epithelial cells that express K12. 8 Several studies have shown that stem cell plasticity and pluripotency is determined by environmental factors.…”

Section: The Limbal Stem Cells and The Stem Cell Nichementioning

confidence: 99%

“…8 The corneal epithelial cells from adult mice have demonstrated abnormal morphology of the nuclei, mitochondria, and cytoskeleton. 7,19,20 PAX6 also regulates the expression of cell adhesion molecules. Davis et al have shown large gaps between corneal epithelial cells and an unusual appearance of the desmosomes in Sey mice.…”

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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: B Oxidative Stress Wound Healing and Corneal Transparencymentioning

confidence: 99%

Section: The Limbal Stem Cells and The Stem Cell Nichementioning

confidence: 99%

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confidence: 99%

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Congenital Aniridia and the Ocular Surface

et al. 2016

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“…Interestingly, a coordinated centripetal movement of epithelial cells and nerves has been postulated in several studies. 38,39 The present study provides the first evidence in human corneas of an exact correspondence of epithelial cell and subbasal nerve patterns of movement, however, as noted in a recent study, 34 the mechanisms orchestrating this motion still remain unclear.…”

Section: Discussionmentioning

confidence: 52%

Pathologic Epithelial and Anterior Corneal Nerve Morphology in Early-Stage Congenital Aniridic Keratopathy

et al. 2012

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Objective: To document the clinical and morphologic corneal findings in the early stages of congenital aniridic keratopathy in Swedish families. less thanbrgreater than less thanbrgreater thanDesign: Prospective, observational, comparative case series. less thanbrgreater than less thanbrgreater thanParticipants: A total of 16 eyes of 16 subjects with congenital aniridic keratopathy and a clear central cornea, and 6 eyes from 6 healthy controls (unaffected relatives). Nine of the 16 eyes with aniridia came from 5 families with a documented familial history of aniridia. less thanbrgreater than less thanbrgreater thanMethods: Detailed ophthalmic examinations included best spectacle-corrected visual acuity (BSCVA), tear film production, tear break-up time (BUT), corneal touch sensitivity, intraocular pressure measurement, ultrasound pachymetry, slit-lamp biomicroscopy, and laser scanning in vivo confocal microscopy (IVCM). less thanbrgreater than less thanbrgreater thanMain Outcome Measures: Confirmed stage of aniridic keratopathy, clinical parameters of cornea and tear film (visual acuity, sensitivity, corneal thickness, tear production, and BUT), and the morphologic status of corneal epithelium, sub-basal nerves, and limbal palisades of Vogt. less thanbrgreater than less thanbrgreater thanResults: In early-stage aniridic keratopathy, BSCVA and tear BUT were reduced relative to controls (P andlt; 0.001 for both), and corneal thickness was increased (P = 0.01). Inflammatory dendritic cells were present in the central epithelium in aniridia, with significantly increased density relative to controls (P = 0.001). Discrete focal opacities in the basal epithelial region were present in 5 of 11 aniridia cases with an otherwise clear cornea. Opacities were associated with dendritic cells and harbored structures presumed to be goblet cells. Sub-basal nerves were extremely dense in 3 aniridia cases, and a prominent whorl pattern of nerves and epithelial cells was observed in 1 case. Normal limbal palisade morphology was absent in aniridia but present in controls. less thanbrgreater than less thanbrgreater thanConclusions: Early-stage aniridic keratopathy is characterized by the development of focal opacities in the basal epithelium, altered sub-basal nerves, infiltration of the central epithelium by dendritic cells, tear film instability, and increased corneal thickness and degradation of limbal palisade architecture. These findings may help to elucidate the pathogenesis of aniridic keratopathy. less thanbrgreater than less thanbrgreater thanFinancial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Funding Agencies|European Union||Crown Princess Margaretas Foundation for the Visually Impaired||Swedish Eye Fund||Carmen and Bertil Regners Foundation||David and Beth Dahlins Foundation||King Gustav V and Queen Victorias Freemasons Foundation||County Council of Ostergotland||Association of the Blind in Ostergotland||

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The limbal epithelium of the eye – A review of limbal stem cell biology, disease and treatment

2012

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The limbus is a narrow band of tissue that encircles the cornea, the transparent 'window' into the eye. The outermost layer of the cornea is the epithelium, which is necessary for clear vision. The limbus acts as a 'reservoir' for limbal stem cells which maintain and regenerate the corneal epithelium. It also functions as a barrier to the conjunctiva and its blood vessels. Limbal stem cell deficiency is a general term for diseases which are characterised by the impairment of the limbus, limbal stem cells and their ability to replenish the corneal epithelium through proliferation and differentiation. Consequently, sufferers experience chronic pain and progressive blindness. This paper will highlight the salient milestones of limbal stem cell biology and potential future treatments for limbal stem cell deficiency.

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Corneal Development, Limbal Stem Cell Function, and Corneal Epithelial Cell Migration in thePax6^+/−Mouse

Cited by 139 publications

References 34 publications

Congenital Aniridia and the Ocular Surface

Congenital Aniridia and the Ocular Surface

Pathologic Epithelial and Anterior Corneal Nerve Morphology in Early-Stage Congenital Aniridic Keratopathy

The limbal epithelium of the eye – A review of limbal stem cell biology, disease and treatment

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Corneal Development, Limbal Stem Cell Function, and Corneal Epithelial Cell Migration in thePax6+/−Mouse

Cited by 139 publications

References 34 publications

Congenital Aniridia and the Ocular Surface

Congenital Aniridia and the Ocular Surface

Pathologic Epithelial and Anterior Corneal Nerve Morphology in Early-Stage Congenital Aniridic Keratopathy

The limbal epithelium of the eye – A review of limbal stem cell biology, disease and treatment

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Corneal Development, Limbal Stem Cell Function, and Corneal Epithelial Cell Migration in thePax6^+/−Mouse