Limbal stem cells

Two-photon excitation microscopy (TPM) and multiphoton fluorescence microscopy (MPM) are advanced forms of intravital high-resolution functional microscopy techniques that allow for the imaging of dynamic molecular processes and resolve features of the biological tissues of interest. Due to the cornea's optical properties and the uniquely accessible position of the globe, it is possible to image cells and tissues longitudinally to investigate ocular surface physiology and disease. MPM can also be used for the in vitro investigation of biological processes and drug kinetics in ocular tissues...

Exposure to air pollutants, especially in the case of particulate matter (PM), poses significant health risks throughout the body. The ocular surface is directly exposed to atmospheric PM making it challenging to avoid. This constant exposure makes the ocular surface a valuable model for investigating the impact of air pollutants on the eyes. This comprehensive review assembles evidence from across the spectrum, from in vitro and in vivo investigations to clinical studies, offering a thorough understanding of how PM10 and PM2...

OBJECTIVES: To examine and to understand the limbal stem-cell deficiency (LSCD) because of Steven-Johnson syndrome (SJS) in line with the new classification system for the first time in the literature. METHODS: Medical records of patients with LSCD because of SJS were reviewed retrospectively. In addition to demographic data and ophthalmologic or systemic findings, anterior segment photographs of the patients were reviewed retrospectively. Limbal stem-cell deficiency severity was graded according to the classification published by the Limbal Stem Cell Working Group...

This literature review will provide a critical narrative overview of the highlights and potential pitfalls of the reported animal models for limbal stem cell deficiency (LSCD) and will identify the neglected aspects of this research area. There exists significant heterogeneity in the literature regarding the methodology used to create the model and the predefined duration after the insult when the model is supposedly fully fit for evaluations and/or for testing various therapeutic interventions. The literature is also replete with examples wherein the implementation of a specific model varies significantly across different studies...

Sulfur mustard (SM), a bi-functional alkylating agent, was used during World War I and the Iran-Iraq war. SM toxicity is ten times higher in eyes than in other tissues. Cornea is exceptionally susceptible to SM-injuries due to its anterior positioning and mucous-aqueous interphase. Ocular SM exposure induces blepharitis, photosensitivity, dry eye, epithelial defects, limbal ischemia and stem cell deficiency, and mustard gas keratopathy leading to temporary or permanent vision impairments. We demonstrated that dexamethasone (Dex) is a potent therapeutic intervention against SM-induced corneal injuries; however, its mechanism of action is not well known...

With the development of regenerative medicine in ophthalmology, the identification of cells with high proliferative potential in the limbal area has attracted the attention of ophthalmologists and offered a new option for treatment in clinical practice. Limbal stem cell deficiency (LSCD) is an identified eye disease with a difficult and negative outcome, for which the traditional treatment is keratoplasty. This study sought to evaluate the efficacy of matrix-assisted cell transplantation consisting of in vitro-cultured autologous limbal stem cells (LSCs) and type I collagen for the treatment of LSCD in rabbits...

Regenerative medicine (RM) has emerged as a promising and revolutionary solution to address a range of unmet needs in healthcare, including ophthalmology. Moreover, RM takes advantage of the body's innate ability to repair and replace pathologically affected tissues. On the other hand, despite its immense promise, RM faces challenges such as ethical concerns, host-related immune responses, and the need for additional scientific validation, among others. The primary aim of this review is to present a high-level overview of current strategies in the domain of RM (cell therapy, exosomes, scaffolds, in vivo reprogramming, organoids, and interspecies chimerism), centering around the field of ophthalmology...

Corneal stromal stem cells (CSSCs) are of particular interest in regenerative ophthalmology, offering a new therapeutic target for corneal injuries and diseases. This review provides a comprehensive examination of CSSCs, exploring their anatomy, functions, and role in maintaining corneal integrity. Molecular markers, wound healing mechanisms, and potential therapeutic applications are discussed. Global corneal blindness, especially in more resource-limited regions, underscores the need for innovative solutions...

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This study compared the long-term outcome of different epithelial transplantation techniques to treat limbal stem cell deficiency (LSCD). We conducted a retrospective 15-year comparative systematic cohort study of patients with LSCD who underwent either cultivated limbal epithelial transplantation (CLET), simple limbal epithelial transplantation (SLET), or cultivated oral mucosal epithelial transplantation (COMET). We reviewed the demographic data, etiology, LSCD severity, best-corrected visual acuity, surgical outcomes, and complications...

Corneal diseases are a major cause of vision loss worldwide. Traditional methods like corneal transplants from donors are effective but face challenges like limited donor availability and the risk of graft rejection. Therefore, new treatment methods are essential. This review examines the growing field of bioprinting and biofabrication in corneal tissue engineering. We begin by discussing various bioprinting methods such as stereolithography, inkjet, and extrusion printing, highlighting their strengths and weaknesses for eye-related uses...

The corneal epithelium (CE) is the outermost layer of the cornea with constant turnover, relative stability, remarkable plasticity, and compensatory properties to mask alterations in the underlying stroma. The advent of quantitative imaging modalities capable of producing epithelial thickness mapping (ETM) has made it possible to characterize better the different patterns of epithelial remodeling. In this comprehensive synthesis, we reviewed all available data on ETM with different methods, including very high-frequency ultrasound (VHF-US) and spectral-domain optical coherence tomography (SD-OCT) in normal individuals, corneal or systemic diseases, and corneal surgical scenarios...

BACKGROUND: Mesenchymal stem cells in the adult corneal stroma (named corneal stromal stem cells, CSSCs) inhibit corneal inflammation and scarring and restore corneal clarity in pre-clinical corneal injury models. This cell therapy could alleviate the heavy reliance on donor materials for corneal transplantation to treat corneal opacities. Herein, we established Good Manufacturing Practice (GMP) protocols for CSSC isolation, propagation, and cryostorage, and developed in vitro quality control (QC) metric for in vivo anti-scarring potency of CSSCs in treating corneal opacities...

Proper differentiation of corneal epithelial cells (CECs) from limbal stem/progenitor cells (LSCs) is required for maintenance of ocular homeostasis and clear vision. Here, using a single-cell transcriptomic atlas, we delineate the comprehensive and refined molecular regulatory dynamics during human CEC development and differentiation. We find that RORA is a CEC-specific molecular switch that initiates and drives LSCs to differentiate into mature CECs by activating PITX1. RORA dictates CEC differentiation by establishing CEC-specific enhancers and chromatin interactions between CEC gene promoters and distal regulatory elements...

The cornea, as a dynamic and responsive tissue, constantly interacts with mechanical forces in order to maintain its structural integrity, barrier function, transparency and refractive power. Cells within the cornea sense and respond to various mechanical forces that fundamentally regulate their morphology and fate in development, homeostasis and pathophysiology. Corneal cells also dynamically regulate their extracellular matrix (ECM) with ensuing cell-ECM crosstalk as the matrix serves as a dynamic signaling reservoir providing biophysical and biochemical cues to corneal cells...

Limbal stem cell deficiency (LSCD) causes severe vision impairment and can lead to blindness, representing one of the most challenging ocular surface disorders. Stem cell deficiency can be congenital or, more often, acquired. The categorization of ocular surface transplantation techniques is crucial to achieving treatment homogeneity and quality of care, according to the anatomic source of the tissue being transplanted, genetic source, autologous or allogenic transplantation (to reflect histocompatibility in the latter group), and cell culture and tissue engi neering techniques...

Human embryonic stem cell (hESC)- and human induced pluripotent stem cell (hiPSC)-derived retinal pigment epithelium (RPE) therapies are promising alternatives for the treatment of retinal degenerative diseases caused by RPE degeneration. The generation of autologous RPE cells from human adult donors, which has the advantage of avoiding immune rejection and teratoma formation, is an alternative cell resource to gain mechanistic insight into and test potential therapies for RPE degenerative diseases. Here, we found that limbal stem cells (LSCs) from hESCs and adult primary human limbus have the potential to produce RPE cells and corneal stromal stem cells (CSSCs)...

PURPOSE: To study the clinical characteristics and treatment outcomes of ocular surface pseudoepitheliomatous hyperplasia (PEH) associated with chronic vernal keratoconjunctivitis (VKC). METHODS: This retrospective study includes 39 eyes of 32 patients with VKC induced PEH who presented from 2016-2022. A database search was conducted for diagnosis of PEH, and data on clinical features, imaging characteristics, and treatment were analyzed. RESULTS: Of the 32 patients, 11 (34%) were children and adolescents, 21 (66%) were adults...

PURPOSE: To determine the safety and feasibility of human autologous adipose tissue-derived adult mesenchymal stem cells (ASCs) for ocular surface regeneration in patients with bilateral limbal stem-cell deficiency (LSCD). METHODS: A phase IIa clinical trial was designed (https://Clinicaltrials.gov, NCT01808378) with 8 patients, 3 of whom had aniridia, 2 meibomian glands diseases, 2 multiple surgeries and 1 chronic chemical injury. The therapeutic protocol was as follows: 6-mm of central corneal epithelium was removed, 400,000 ASCs were injected into each limboconjunctival quadrant, 400,000 ASCs were suspended over the cornea for 20 min, and finally the cornea was covered with an amniotic membrane patch...

ABCB5 is a member of the ABC transporter superfamily composed of 48 transporters, which have been extensively studied for their role in cancer multidrug resistance and, more recently, in tumorigenesis. ABCB5 has been identified as a marker of skin progenitor cells, melanoma, and limbal stem cells. It has also been associated with multidrug resistance in several cancers. The unique feature of ABCB5 is that it exists as both a full transporter (ABCB5FL) and a half transporter (ABCB5β). Several studies have shown that the ABCB5β homodimer does not confer multidrug resistance, in contrast to ABCB5FL...