Wound healing of the corneal epithelium: a review (original) (raw)
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Corneal Repair and Regeneration: Current Concepts and Future Directions
Frontiers in Bioengineering and Biotechnology, 2019
The cornea is a unique tissue and the most powerful focusing element of the eye, known as a window to the eye. Infectious or non-infectious diseases might cause severe visual impairments that need medical intervention to restore patients' vision. The most prominent characteristics of the cornea are its mechanical strength and transparency, which are indeed the most important criteria considerations when reconstructing the injured cornea. Corneal strength comes from about 200 collagen lamellae which criss-cross the cornea in different directions and comprise nearly 90% of the thickness of the cornea. Regarding corneal transparency, the specific characteristics of the cornea include its immune and angiogenic privilege besides its limbus zone. On the other hand, angiogenic privilege involves several active cascades in which anti-angiogenic factors are produced to compensate for the enhanced production of proangiogenic factors after wound healing. Limbus of the cornea forms a border between the corneal and conjunctival epithelium, and its limbal stem cells (LSCs) are essential in maintenance and repair of the adult cornea through its support of corneal epithelial tissue repair and regeneration. As a result, the main factors which threaten the corneal clarity are inflammatory reactions, neovascularization, and limbal deficiency. In fact, the influx of inflammatory cells causes scar formation and destruction of the limbus zone. Current studies about wound healing treatment focus on corneal characteristics such as the immune response, angiogenesis, and cell signaling. In this review, studied topics related to wound healing and new approaches in cornea regeneration, which are mostly related to the criteria mentioned above, will be discussed.
Corneal epithelial wound healing
British Journal of Ophthalmology, 1994
property is dependent in part on the ability of the corneal epithelium to undergo continuous renewal. Epithelial renewal is essential because it enables this tissue to act as a barrier that protects the corneal interior from becoming infected by noxious environmental agents. Furthermore, the smooth optical properties of the corneal epithelial surface are sustained through this renewal process. The rate of renewal is dependent on a highly integrated balance between the processes of corneal epithelial proliferation, differentiation, and cell death. One experimental approach to characterize these three aspects of the renewal process has been to study the kinetics and dynamics of corneal re-epithelialization in a wound-healing model. This effort has employed in vivo and in vitro studies. From such studies it is evident that the appropriate integration and coordination of corneal epithelial proliferation, adhesion, migration, and cell demise is dependent on the actions of a myriad of cytokines. Our goal here is to provide an overview into how these mediators and environmental factors elicit control of cellular proliferation, adhesion, migration, and apoptosis. To this end we review the pertinent literature dealing with the receptor and the cell signaling events that are responsible for mediating cytokine control of corneal epithelial renewal. It is our hope that a better appreciation can be obtained about the complexity of the control processes that are responsible for assuring continuous corneal epithelial renewal in health and disease.
Biological modulation of corneal epithelial wound healing
Arquivos Brasileiros de Oftalmologia
The transparency and maintenance of corneal epithelial integrity are essential for its optical properties and, to preserve these characteristics, the epithelium undergoes continuous renewal. This renewal depends on the control of cell proliferation and differentiation mediated by mitogenic factors responsible for increasing mitoses and stimulating cellular migration. Cell-cell communication plays a pivotal role in epithelial healing process, and several cytokines and growth factors are involved in this process. Understanding the cross-talk and paracrine effects of these cytokines and growth factors released can help in the search for new therapeutic strategies to treat ocular surface diseases.
Translational Research in Corneal Epithelial Wound Healing
Eye & Contact Lens: Science & Clinical Practice, 2010
To review both the roles of fibronectin and the sensory neurotransmitter substance P in corneal epithelial wound healing and the clinical application of these agents to treat persistent corneal epithelial defects. Results: Fibronectin is expressed at the site of corneal epithelial defects, serves as a provisional matrix for the migration of epithelial cells, and stimulates epithelial wound healing in vitro and in animal models. Eyedrops containing autologous plasma fibronectin are also effective for the treatment of persistent epithelial defects of the cornea in patients. Substance P and insulin-like growth factor-1 synergistically stimulate corneal epithelial wound healing in vitro and in animal models. Furthermore, the administration of eyedrops containing both a substance P-derived peptide (FGLM-amide) and insulin-like growth factor-1-derived peptide (SSSR) is effective for the treatment of persistent epithelial defects in individuals with neurotrophic keratopathy. Conclusions: Basic research on the mechanism of corneal epithelial wound healing has the potential to lead to the development of new modes of treatment for persistent corneal epithelial defects. Clinical experience with eyedrops containing fibronectin or both FGLM-amide and SSSR has highlighted the importance of the basement membrane and neural stimuli in maintenance of the integrity of the normal corneal epithelium.
Investigative Ophthalmology & Visual Science, 2008
PURPOSE. The reepithelialization of the corneal surface is an important process for restoring the imaging properties of this tissue. The purpose of the present study was to characterize and validate a new human in vitro three-dimensional corneal wound healing model by studying the expression of basement membrane components and integrin subunits that play important roles during epithelial cell migration and to verify whether the presence of exogenous factors could accelerate the reepithelialization. METHODS. Tissue-engineered human cornea was wounded with a 6-mm biopsy punch, and the reepithelialization from the surrounding margins was studied. Biopsy samples of the reepithelialized surface were harvested 3 days after wounding and were processed for histologic, electron microscopic, and immunofluorescence analyses. The effects of fibrin and epithelial growth factor (EGF) on wound reepithelialization were also studied. RESULTS. Results demonstrated that this in vitro model allowed the migration of human corneal epithelial cells on a natural extracellular matrix. During reepithelialization, epithelial cell migration followed a consistent wavelike pattern similar to that reported for human corneal wound healing in vivo. This model showed a histologic appearance similar to that of native tissue as well as expression and modulation of basement membrane components and the integrin subunits known to be main actors during the wound healing process. It also allowed quantification of the reepithelialization rate, which was significantly accelerated in the presence of fibrin or EGF. The results indicated that ␣ v  6 integrin expression was increased in the mi-grating epithelial cells compared with the surrounding corneal tissue. CONCLUSIONS. The similarity observed with the in vivo wound healing process supports the use of this tissue-engineered model for investigating the basic mechanisms involved in corneal reepithelialization. Moreover, this model may also be used as a tool to screen agents that affect reepithelialization or to evaluate the effect of growth factors before animal testing.
Acta Ophthalmologica, 2014
This study was performed to evaluate the potential of a collagen-based membrane, collagen vitrigel (CV), for reconstructing corneal epithelium in the stromal wound and limbal stem cell deficiency (LSCD) models. Methods: Three groups of rabbits were used in the stromal wound model: CV affixed using fibrin glue (CV + FG group, n = 9), fibrin glue only (FG group, n = 3) and an untreated control group (n = 3). In the LSCD model, one group received CV containing human limbal epithelial cells (CV + hLEC group, n = 2) and the other was an untreated control (n = 1). Gross observation, including fluorescent staining, pathological examination, immunohistochemistry and electron microscopy, was used to evaluate the effect of CV on the corneal epithelium. Results: In the stromal wound model, fluorescent staining showed that epithelial reconstruction occurred as rapidly in the CV + FG group as it did in the control group. The pathological examination proved that the CV supported a healthy corneal epithelium in the CV + FG group, whereas FG led to hypertrophy and inappropriate differentiation of corneal epithelium in the FG group. In the LSCD model, the corneas in the CV + hLEC group showed sustained tissue transparency with good epithelialization, low inflammatory response and reduced neovascularization. However, the control cornea was translucent and showed high amounts of inflammation and neovascularization. Conclusion: We have demonstrated that CV supports corneal epithelial differentiation and prevents epithelial hypertrophy, in addition to serving as a scaffold for hLEC transplantation, without complications.
Concise Review: Stem Cells for Corneal Wound Healing
STEM CELLS
Corneal wound healing is a complex process that occurs in response to various injuries and commonly used refractive surgery. It is a significant clinical problem, which may lead to serious complications due to either incomplete (epithelial) or excessive (stromal) healing. Epithelial stem cells clearly play a role in this process, whereas the contribution of stromal and endothelial progenitors is less well studied. The available evidence on stem cell participation in corneal wound healing is reviewed, together with the data on the use of corneal and non-corneal stem cells to facilitate this process in diseased or postsurgical conditions. Important aspects of corneal stem cell generation from alternative cell sources, including pluripotent stem cells, for possible transplantation upon corneal injuries or in disease conditions are also presented.
Cornea, 2005
Purpose: The corneal wound healing response is of particular relevance for refractive surgical procedures since it is a major determinant of efficacy and safety. The purpose of this review is to provide an overview of the healing response in refractive surgery procedures. Methods: Literature review. Results: LASIK and PRK are the most common refractive procedures; however, alternative techniques, including LASEK, PRK with mitomycin C, and Epi-LASIK, have been developed in an attempt to overcome common complications. Clinical outcomes and a number of common complications are directly related to the healing process and the unpredictable nature of the associated corneal cellular response. These complications include overcorrection, undercorrection, regression, corneal stroma opacification, and many other side effects that have their roots in the biologic response to surgery. The corneal epithelium, stroma, nerves, inflammatory cells, and lacrimal glands are the main tissues and organs involved in the wound healing response to corneal surgical procedures. Complex cellular interactions mediated by cytokines and growth factors occur among the cells of the cornea, resulting in a highly variable biologic response. Among the best characterized processes are keratocyte apoptosis, keratocyte necrosis, keratocyte proliferation, migration of inflammatory cells, and myofibroblast generation. These cellular interactions are involved in extracellular matrix reorganization, stromal remodeling, wound contraction, and several other responses to surgical injury. Conclusions: A better understanding of the complete cascade of events involved in the corneal wound healing process and anomalies that lead to complications is critical to improve the efficacy and safety of refractive surgical procedures. Recent advances in understanding the biologic and molecular processes that contribute to the healing response bring hope that safe and effective pharmacologic modulators of the corneal wound healing response may soon be developed.
The conjunctiva in corneal epithelial wound healing
British Journal of Ophthalmology, 1998
Background/aims-During the healing of corneal epithelial wounds with limbal involvement, conjunctival epithelium often migrates across the denuded limbus to cover the corneal surface. It is believed that, over a period of time, conjunctival epithelium covering the cornea assumes characteristics of corneal epithelium by a process referred to as conjunctival transdiVerentiation. The purpose of this study was to examine, clinically, the fate of conjunctival epithelial cells covering the cornea and to assess the healing of corneal epithelial wounds when the conjunctival epithelium was removed or actively prevented from crossing the limbus and extending onto the cornea. Methods-10 patients with conjunctivalisation of the cornea were followed for an average of 7.5 months. Five patients in this group had their conjunctival epithelium removed from the corneal surface and allowed to heal from the remaining intact corneal epithelium. In another four patients with corneal epithelial defects, the conjunctival epithelium was actively prevented from crossing the limbus by mechanically scraping it oV. Results-The area of cornea covered by conjunctival epithelium appeared thin, irregular, attracted new vessels and was prone to recurrent erosions. Conjunctivalisation of the visual axis aVected vision. Removal of conjunctival epithelium from the cornea allowed cells of corneal epithelial phenotype to cover the denuded area with alleviation of symptoms and improvement of vision. It was also established that migration of conjunctival epithelium onto corneal surface could be anticipated by close monitoring of the healing of corneal epithelial wounds, and prevented by scraping oV conjunctival epithelium before it reached the limbus. Conclusion-This study shows that there is little clinical evidence to support the concept that conjunctival transdiVerentiation per se, occurs in humans. "Replacement" of conjunctival epithelium by corneal epithelial cells may be an important mechanism by which conjunctival "transdiVerentiation" may occur. In patients with partial stem cell deficiency this approach can be a useful and eVective alternative to partial limbal transplantation, as is currently practised.