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Biology
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Limbal Stem Cell Biology and Contribution to Cornea Homeostasis
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Limbal Stem Cell Biology and Contribution to Cornea Homeostasis

A special issue of Biology (ISSN 2079-7737).

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 10735

Special Issue Editor

Dr. Maria Notara

E-Mail Website
Guest Editor
Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpenerstr. 62, 50937 Cologne, Germany
Interests: stem cells; (lymph) angiogenesis; UV irradiation; DNA damage

Special Issue Information

Dear Colleagues,

Corneal epithelium integrity is essential for cornea function and, essentially, for good vision. It is replenished by a population of limbal epithelial stem cells (LESCs), which reside at the limbus, the vascularised corneoscleral junction between the cornea and conjunctiva. LESCs function is essential for cornea homeostasis, as they play multiple roles, contributing to corneal epithelium stability by providing stable and timely new cells, by their signalling in the niche and beyond and by affecting corneal avascularity and absence of inflammation. When this stem cell population is compromised due to disease, injury or environmental factors (e.g., UV irradiation), the cornea becomes opaque, vascularised, inflamed and opaque, leading to patient discomfort and ultimately, blindness. In recent years, LESC transplantation has offered a therapeutic option, which helps successfully restore cornea morphology, transparency and visual acuity.

We are pleased to invite you to contribute to this Special Issue, entitled: Limbal Stem Cell Biology and Contribution to Cornea Homeostasis.

This Special Issue aims to highlight what we currently know on the role of LESCs in cornea stability, with a special focus on how they impact on corneal immune and angiogenic privilege, the signaling mechanisms involved in their own maintenance within the niche micro milieu, as well as their transition to the fast-replicating transient amplifying and fully differentiated corneal epithelial cells, and the curative effect on the corneal epithelial tissue upon transplantation.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

  • The role of LESC in corneal epithelial morphogenesis;
  • LESC polarity and mechanisms of differentiation;
  • LESC cross-talk with other cell types in the niche;
  • LESCs and cornea immune privilege;
  • The role of LESCs in cornea avascularity;
  • The restorative effect of LESC transplantation.

We look forward to receiving your contributions.

Dr. Maria Notara
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biology is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • limbal epithelial stem cells
  • niche signaling
  • (lymph) angiogenesis
  • LESC transplantation
  • LESC morphogenesis
  • LESC deficiency

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Published Papers (4 papers)

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Research

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23 pages, 2274 KiB  
Article
A Keratin 12 Expression-Based Analysis of Stem-Precursor Cells and Differentiation in the Limbal–Corneal Epithelium Using Single-Cell RNA-Seq Data
by J. Mario Wolosin
Biology 2024, 13(3), 145; https://doi.org/10.3390/biology13030145 - 26 Feb 2024
Cited by 1 | Viewed by 1782
Abstract
The corneal epithelium (CE) is spread between two domains, the outer vascularized limbus and the avascular cornea proper. Epithelial cells undergo constant migration from the limbus to the vision-critical central cornea. Coordinated with this migration, the cells undergo differentiation changes where a pool [...] Read more.
The corneal epithelium (CE) is spread between two domains, the outer vascularized limbus and the avascular cornea proper. Epithelial cells undergo constant migration from the limbus to the vision-critical central cornea. Coordinated with this migration, the cells undergo differentiation changes where a pool of unique stem/precursor cells at the limbus yields the mature cells that reach the corneal center. Differentiation is heralded by the expression of the corneal-specific Krt12. Processing data acquired by scRNA-Seq showed that the increase in Krt12 expression occurs in four distinct steps within the limbus, plus a single continuous increase in the cornea. Differential gene analysis demonstrated that these domains reflect discreet stages of CE differentiation and yielded extensive information of the genes undergoing down- or upregulation in the sequential transition from less to more differentiate conditions. The approach allowed the identification of multiple gene cohorts, including (a) the genes which have maximal expression in the most primitive, Krt12-negative cell cohort, which is likely to include the stem/precursor cells; (b) the sets of genes that undergo continuous increase or decrease along the whole differentiation path; and (c) the genes showing maximal positive or negative correlation with the changes in Krt12. Full article
(This article belongs to the Special Issue Limbal Stem Cell Biology and Contribution to Cornea Homeostasis)
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19 pages, 6872 KiB  
Article
Short-Term UVB Irradiation Leads to Persistent DNA Damage in Limbal Epithelial Stem Cells, Partially Reversed by DNA Repairing Enzymes
by Thomas Volatier, Björn Schumacher, Berbang Meshko, Karina Hadrian, Claus Cursiefen and Maria Notara
Biology 2023, 12(2), 265; https://doi.org/10.3390/biology12020265 - 7 Feb 2023
Cited by 2 | Viewed by 2468
Abstract
The cornea is frequently exposed to ultraviolet (UV) radiation and absorbs a portion of this radiation. UVB in particular is absorbed by the cornea and will principally damage the topmost layer of the cornea, the epithelium. Epidemiological research shows that the UV damage [...] Read more.
The cornea is frequently exposed to ultraviolet (UV) radiation and absorbs a portion of this radiation. UVB in particular is absorbed by the cornea and will principally damage the topmost layer of the cornea, the epithelium. Epidemiological research shows that the UV damage of DNA is a contributing factor to corneal diseases such as pterygium. There are two main DNA photolesions of UV: cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6–4) photoproducts (6-4PPs). Both involve the abnormal linking of adjacent pyrimide bases. In particular, CPD lesions, which account for the vast majority of UV-induced lesions, are inefficiently repaired by nucleotide excision repair (NER) and are thus mutagenic and linked to cancer development in humans. Here, we apply two exogenous enzymes: CPD photolyase (CPDPL) and T4 endonuclease V (T4N5). The efficacy of these enzymes was assayed by the proteomic and immunofluorescence measurements of UVB-induced CPDs before and after treatment. The results showed that CPDs can be rapidly repaired by T4N5 in cell cultures. The usage of CPDPL and T4N5 in ex vivo eyes revealed that CPD lesions persist in the corneal limbus. The proteomic analysis of the T4N5-treated cells shows increases in the components of the angiogenic and inflammatory systems. We conclude that T4N5 and CPDPL show great promise in the treatment of CPD lesions, but the complete clearance of CPDs from the limbus remains a challenge. Full article
(This article belongs to the Special Issue Limbal Stem Cell Biology and Contribution to Cornea Homeostasis)
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Review

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17 pages, 694 KiB  
Review
The Role of Insulin-like Growth Factor (IGF) System in the Corneal Epithelium Homeostasis—From Limbal Epithelial Stem Cells to Therapeutic Applications
by Małgorzata Woronkowicz, Harry Roberts and Piotr Skopiński
Biology 2024, 13(3), 144; https://doi.org/10.3390/biology13030144 - 25 Feb 2024
Viewed by 2749
Abstract
The corneal epithelium, comprising three layers of cells, represents the outermost portion of the eye and functions as a vital protective barrier while concurrently serving as a critical refractive structure. Maintaining its homeostasis involves a complex regenerative process facilitated by the functions of [...] Read more.
The corneal epithelium, comprising three layers of cells, represents the outermost portion of the eye and functions as a vital protective barrier while concurrently serving as a critical refractive structure. Maintaining its homeostasis involves a complex regenerative process facilitated by the functions of the lacrimal gland, tear film, and corneal nerves. Crucially, limbal epithelial stem cells located in the limbus (transitional zone between the cornea and the conjunctiva) are instrumental for the corneal epithelium integrity by replenishing and renewing cells. Re-epithelialization failure results in persistent defects, often associated with various ocular conditions including diabetic keratopathy. The insulin-like growth factor (IGF) system is a sophisticated network of insulin and other proteins essential for numerous physiological processes. This review examines its role in maintaining the corneal epithelium homeostasis, with a special focus on the interplay with corneal limbal stem cells and the potential therapeutic applications of the system components. Full article
(This article belongs to the Special Issue Limbal Stem Cell Biology and Contribution to Cornea Homeostasis)
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19 pages, 1576 KiB  
Review
A Review of Contact Lens-Induced Limbal Stem Cell Deficiency
by Yhu Fhei Lee, Dayna Wei Wei Yong and Ray Manotosh
Biology 2023, 12(12), 1490; https://doi.org/10.3390/biology12121490 - 5 Dec 2023
Cited by 2 | Viewed by 2837
Abstract
Limbal stem cell deficiency (LSCD) is a pathologic condition caused by the dysfunction and destruction of stem cells, stem cell precursors and limbal cell niche in the corneal epithelium, leading to severe conjunctivalization of the cornea. Etiologies for LSCD span from congenital (aniridia), [...] Read more.
Limbal stem cell deficiency (LSCD) is a pathologic condition caused by the dysfunction and destruction of stem cells, stem cell precursors and limbal cell niche in the corneal epithelium, leading to severe conjunctivalization of the cornea. Etiologies for LSCD span from congenital (aniridia), traumatic (chemical or thermal injuries), autoimmune (Stevens–Johnson syndrome) and iatrogenic disease to contact lens (CL) wear. Of these, CL wear is the least understood and is often a subclinical cause of LSCD. Even with recent advances in LSCD research, limitations persist in establishing the pathogenesis and treatment guidelines for CL-induced LSCD. A literature search was conducted to include original articles containing patients with CL-induced LSCD. This review will critically discuss the complex pathophysiology behind CL-induced LSCD, the underlying risk factors and epidemiology of the disease as well as methods to obtain a diagnosis. Various treatment options will be reviewed based on proposed treatment strategies. Full article
(This article belongs to the Special Issue Limbal Stem Cell Biology and Contribution to Cornea Homeostasis)
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