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Experimental Eye Research Dec 2018There has been a drive to develop new cell based therapies to treat corneal blindness, one of the most common causes of blindness worldwide. Mechanical and physical cues... (Review)
Review
There has been a drive to develop new cell based therapies to treat corneal blindness, one of the most common causes of blindness worldwide. Mechanical and physical cues are known to regulate the behavior of many cell types, however studies examining these effects on corneal epithelial cells have been limited in number and their findings have not previously been amalgamated and contrasted. Here, we provide an overview of the different types of mechanical stimuli to which the corneal epithelium is exposed and the influence that these have on the cells. Shear stress from the tear film motion and blinking, extracellular matrix stiffness and external physical forces such as eye rubbing and contact lens wear are among some of the forms of mechanical stimuli that the epithelium experiences. In vivo and in vitro studies examining the mechanobiology on corneal epithelial cells under differing mechanical environments are explored. A greater understanding of the mechanobiology of the corneal epithelium has the potential to lead to improved tissue engineering and cell based therapies to repair and regenerate damaged cornea.
Topics: Corneal Diseases; Epithelium, Corneal; Extracellular Matrix; Eyelids; Humans; Regenerative Medicine; Stress, Mechanical; Tears
PubMed: 30086260
DOI: 10.1016/j.exer.2018.08.001 -
Biological & Pharmaceutical Bulletin 2021The corneal epithelium is continuously exposed to oxygen, light, and environmental substances. Excessive exposure to those stresses is thought to be a risk factor for...
The corneal epithelium is continuously exposed to oxygen, light, and environmental substances. Excessive exposure to those stresses is thought to be a risk factor for eye diseases. Photokeratitis is damage to the corneal epithelium resulting in a painful eye condition caused by unprotected exposure to UV rays, usually from sunlight, and is often found in people who spend a long time outdoors. In modern life, human eyes are exposed to artificial light from light-emitting diode (LED) displays of computers and smartphones, and it has been shown that short-wavelength (blue) LED light can damage eyes, especially photoreceptors. However, the effect of blue LED light on the cornea is less understood. In addition, it is important to develop new treatments for preserving human eyesight and eye health from light stress. Here, we used human corneal epithelial cells-transformed (HCE-T) cells as an in-vitro model to investigate the protective effect of NSP-116, an imidazolyl aniline derivative, against the oxidative stress induced by light in the corneal epithelium. Treatment with 10 µM NSP-116 significantly increased the cell viability and reduced the death ratio following UV or blue LED light exposure. Furthermore, NSP-116 treatment decreased light-induced reactive oxygen species production and preserved the mitochondrial membrane potential. Immunoblotting data showed that NSP-116 suppressed the stress response pathway. Finally, NSP-116 treatment prevented corneal epithelial apoptosis induced by blue LED light in an in-vivo mouse model. In conclusion, NSP-116 has a protective effect against oxidative stress and corneal cell death from both UV and blue LED light exposure.
Topics: Aniline Compounds; Animals; Cell Death; Cell Line; Cell Survival; Corneal Injuries; Epithelial Cells; Epithelium, Corneal; Free Radical Scavengers; Humans; Imidazoles; Light; Male; Membrane Potential, Mitochondrial; Mice; Radiation Injuries, Experimental; Radiation-Protective Agents; Reactive Oxygen Species
PubMed: 34193689
DOI: 10.1248/bpb.b21-00017 -
International Journal of Molecular... Oct 2022Corneal blindness is the fifth leading cause of blindness worldwide, and therapeutic options are still often limited to corneal transplantation. The corneal epithelium... (Review)
Review
Corneal blindness is the fifth leading cause of blindness worldwide, and therapeutic options are still often limited to corneal transplantation. The corneal epithelium has a strong barrier function, and regeneration is highly dependent on limbal stem cell proliferation and basement membrane remodeling. As a result of the lack of corneal donor tissues, regenerative medicine for corneal diseases affecting the epithelium is an area with quite advanced basic and clinical research. Surgery still plays a prominent role in the treatment of epithelial diseases; indeed, innovative surgical techniques have been developed to transplant corneal and non-corneal stem cells onto diseased corneas for epithelial regeneration applications. The main goal of applying regenerative medicine to clinical practice is to restore function by providing viable cells based on the use of a novel therapeutic approach to generate biological substitutes and improve tissue functions. Interest in corneal epithelium rehabilitation medicine is rapidly growing, given the exposure of the corneal outer layers to external insults. Here, we performed a review of basic, clinical and surgical research reports on regenerative medicine for corneal epithelial disorders, classifying therapeutic approaches according to their macro- or microscopic target, i.e., into cellular or subcellular therapies, respectively.
Topics: Humans; Epithelium, Corneal; Corneal Diseases; Cornea; Stem Cells; Blindness; Epithelial Cells
PubMed: 36361918
DOI: 10.3390/ijms232113114 -
Current Opinion in Ophthalmology Jul 2017The aim of this review is to describe the underlying mechanisms of corneal epithelial homeostasis in addition to illustrating the vital role of the limbal epithelial... (Review)
Review
PURPOSE OF REVIEW
The aim of this review is to describe the underlying mechanisms of corneal epithelial homeostasis in addition to illustrating the vital role of the limbal epithelial stem cells (LESCs) and the limbal niche in epithelial regeneration and wound healing.
RECENT FINDINGS
The shedded corneal epithelial cells are constantly replenished by the LESCs which give rise to epithelial cells that proliferate, differentiate, and migrate centripetally. While some recent studies have proposed that epithelial stem cells may also be present in the central cornea, the predominant location for the stem cells is the limbus. The limbal niche is the specialized microenvironment consisting of cells, extracellular matrix, and signaling molecules that are essential for the function of LESCs. Disturbances to limbal niche can result in LESC dysfunction; therefore, limbal stem cell deficiency should also be considered a limbal niche deficiency. Current and in-development therapeutic strategies are aimed at restoring the limbal niche, by medical and/or surgical treatments, administration of trophic factors, and cell based therapies.
SUMMARY
The corneal epithelium is constantly replenished by LESCs that are housed within the limbal niche. The limbal niche is the primary determinant of the LESC function and novel therapeutic approaches should be focused on regeneration of this microenvironment.
Topics: Cell Differentiation; Cell Proliferation; Corneal Diseases; Epithelial Cells; Epithelium, Corneal; Homeostasis; Humans; Limbus Corneae; Stem Cells; Wound Healing
PubMed: 28399066
DOI: 10.1097/ICU.0000000000000378 -
Journal of Cell Science Mar 2017The corneal epithelium acts as a protective barrier on the anterior ocular surface and is essential for maintaining transparency of the cornea and thus visual acuity.... (Review)
Review
The corneal epithelium acts as a protective barrier on the anterior ocular surface and is essential for maintaining transparency of the cornea and thus visual acuity. During both homeostasis and repair, the corneal epithelium is maintained by self-renewing stem cells, which persist throughout the lifetime of the organism. Importantly, as in other self-renewing tissues, the functional activity of corneal epithelial stem cells (CSCEs) is tightly regulated by the surrounding microenvironment, or niche, which provides a range of cues that maintain the stem cell population. This Cell Science at a Glance article and the accompanying poster will therefore aim to summarise our current understanding of the corneal epithelial stem cell niche and its role in regulating stem cell activity during homeostasis, repair and disease.
Topics: Animals; Epithelium, Corneal; Humans; Models, Biological; Stem Cell Niche; Stem Cells
PubMed: 28202689
DOI: 10.1242/jcs.198119 -
Investigative Ophthalmology & Visual... Jan 2017Autophagy and macropinocytosis are processes that are vital for cellular homeostasis, and help cells respond to stress and take up large amounts of material,... (Review)
Review
Autophagy and macropinocytosis are processes that are vital for cellular homeostasis, and help cells respond to stress and take up large amounts of material, respectively. The limbal and corneal epithelia have the machinery necessary to carry out both processes; however, autophagy and macropinocytosis are relatively understudied in these two epithelia. In this Perspectives, we describe the basic principles behind macropinocytosis and autophagy, discuss how these two processes are regulated in the limbal and corneal epithelia, consider how these two processes impact on the physiology of limbal and corneal epithelia, and elaborate on areas of future research in autophagy and macropinocytosis as related to the limbal/corneal epithelia.
Topics: Animals; Autophagy; Epithelium, Corneal; Humans; Limbus Corneae; Pinocytosis
PubMed: 28118670
DOI: 10.1167/iovs.16-21111 -
International Journal of Molecular... Apr 2021The cornea, while appearing to be simple tissue, is actually an extremely complex structure. In order for it to retain its biomechanical and optical properties, perfect... (Review)
Review
The cornea, while appearing to be simple tissue, is actually an extremely complex structure. In order for it to retain its biomechanical and optical properties, perfect organization of its cells is essential. Proper regeneration is especially important after injuries and in the course of various diseases. Eph receptors and ephrin are mainly responsible for the proper organization of tissues as well as cell migration and communication. In this review, we present the current state of knowledge on the role of Eph and ephrins in corneal physiology and diseases, in particular, we focused on the functions of the epithelium and endothelium. Since the role of Eph and ephrins in the angiogenesis process has been well established, we also analyzed their influence on conditions with corneal neovascularization.
Topics: Animals; Cornea; Corneal Diseases; Corneal Neovascularization; Endothelium, Corneal; Ephrins; Epithelium, Corneal; Humans; Molecular Targeted Therapy; Receptors, Eph Family
PubMed: 33925443
DOI: 10.3390/ijms22094567 -
Survey of Ophthalmology 2017Drugs across many pharmacologic classes induce corneal epithelial changes. Many of these drugs have cationic amphiphilic structures, with a hydrophobic ring and... (Review)
Review
Drugs across many pharmacologic classes induce corneal epithelial changes. Many of these drugs have cationic amphiphilic structures, with a hydrophobic ring and hydrophilic cationic amine side chain that allow them to cross cell membranes. These drugs lead to intracellular phospholipid accumulation, often manifested in the cornea by vortex keratopathy, with no effect on visual acuity and few ocular symptoms. Other drugs, notably antineoplastic agents, produce a fine diffuse corneal haze, sometimes accompanied by decreased vision that can be dose limiting. Still other medications cause crystalline epithelial precipitation that might require debridement for resolution. An understanding of the variety of drugs involved, the multiple mechanisms responsible, and the systemic diseases that produce similar changes can lead to improved management strategies for patients with corneal epithelial deposits. In most cases, drug therapy need not be modified or discontinued, but if visual acuity is affected, close collaboration with the prescribing physician can result in determining an optimized dose that treats systemic disease and minimizes these deposits. Additionally, close monitoring might be required if the drug is also associated with other ocular findings, such as optic neuropathy or retinopathy.
Topics: Corneal Diseases; Epithelium, Corneal; Humans
PubMed: 27890620
DOI: 10.1016/j.survophthal.2016.11.008 -
Journal of Cataract and Refractive... Dec 2018This review compared the clinical results of transepithelial corneal crosslinking (CXL) to epithelium-off (epi-off) CXL in progressive corneal ectasia using a... (Review)
Review
This review compared the clinical results of transepithelial corneal crosslinking (CXL) to epithelium-off (epi-off) CXL in progressive corneal ectasia using a metaanalysis. The Cochrane databases and Medline were searched for randomized controlled trials (RCTs). Seven RCTs involving 505 eyes that met the eligibility criteria were identified. The epi-off CXL group showed significantly better outcomes in postoperative changes in maximum keratometry (K) during 1-year observation periods. Transepithelial CXL resulted in significantly greater post-treatment central corneal thickness and best spectacle-corrected visual acuity (BSCVA). The presence of a postoperative demarcation line was significantly more frequent after epi-off CXL than that after transepithelial CXL. No statistically significant difference was found between other parameters. Although patients in the transepithelial CXL group demonstrated a greater improvement in BSCVA compared with patients in the epi-off CXL group at the 1 year follow-up, transepithelial CXL had less impact on halting progressive corneal ectasia in terms of maximum K than epi-off CXL.
Topics: Collagen; Corneal Diseases; Corneal Topography; Cross-Linking Reagents; Dilatation, Pathologic; Epithelium, Corneal; Humans; Photochemotherapy; Photosensitizing Agents; Riboflavin
PubMed: 30314751
DOI: 10.1016/j.jcrs.2018.08.021 -
Cells Sep 2021In the human cornea, regeneration of the epithelium is regulated by the stem cell reservoir of the limbus, which is the marginal region of the cornea representing the... (Review)
Review
In the human cornea, regeneration of the epithelium is regulated by the stem cell reservoir of the limbus, which is the marginal region of the cornea representing the anatomical and functional border between the corneal and conjunctival epithelium. In support of this concept, extensive limbal damage, e.g., by chemical or thermal injury, inflammation, or surgery, may induce limbal stem cell deficiency (LSCD) leading to vascularization and opacification of the cornea and eventually vision loss. These acquired forms of limbal stem cell deficiency may occur uni- or bilaterally, which is important for the choice of treatment. Moreover, a variety of inherited diseases, such as congenital aniridia or dyskeratosis congenita, are characterized by LSCD typically occurring bilaterally. Several techniques of autologous and allogenic stem cell transplantation have been established. The limbus can be restored by transplantation of whole limbal grafts, small limbal biopsies or by ex vivo-expanded limbal cells. In this review, the physiology of the corneal epithelium, the pathophysiology of LSCD, and the therapeutic options will be presented.
Topics: Animals; Cornea; Corneal Diseases; Epithelial Cells; Epithelium, Corneal; Humans; Stem Cell Transplantation; Stem Cells
PubMed: 34571952
DOI: 10.3390/cells10092302