Prolonged Inflammation and Infectious Changes in the Corneal Epithelium Are Associated with Persistent Epithelial Defect (PED) (original) (raw)
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Coordinated activation of corneal wound response genes in vivo as observed by in situ hybridization
Experimental Eye Research, 1995
We used subtractive screening of a cDNA library prepared from corneoscleral rims after cauterizing rat corneas. We identified 76 clones whose corresponding mR.NA increased during the wound healing process in an in vivo model of injury which damages the corneal epithelium, stroma, and endothelium. Of these clones, 31 sequences encode known proteins. Another 45 clones are novel sequences based on comparison with the GenBank/EMBL databases. Changes in the level of expression of the novel genes, and a selected number of the known genes, were examined by in situ hybridization 22 and 72 hr after corneal injury. The majority produced a 'wound pattern' of expression such that the mKNAs were highly induced in all cell types adjacent to the wound site at 22 hr post injury. This signal decreased in intensity with distance from the wound site. In a subset of corneoscleral rims examined by in situ hybridization, the mRNAs for these genes were also highly induced in the limbal epithelium, where the progenitor corneal epithelial stem cells reside. By 72 hr, when acute tissue damage had been repaired, the induced mRNA was only faintly present in the thickened epithelium. Our results provide a useful framework for further studies defining the pathophysiological roles of the known and novel proteins encoded by the isolated cDNA clones.
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.
31 Towards an Integrative View of Corneal Proteomics in Epithelial Wound Healing
2016
Corneal epithelial wound healing is a continuous and multistep process involves cell migration proliferation and differentiation after an injury. Any defect in these processes will result in loss of corneal transparency and function. Around 135 million people are visually impaired, which illustrate the need for better understanding of corneal healing mechanisms and development of efficient ways to accelerate and improve wound healing. Delayed corneal wound healing contains the risk of bacterial infection causes corneal opacity and neovascularization that could lead to corneal blindness. It is therefore important that epithelium should rapidly regenerate after an injury. Reepithelialization involves cell migration proliferation and differentiation to restore the cornea to its highly organized architecture. The molecular mechanisms underlying these processes are yet to be established. Hence the identification of various proteins that could associate with healing process is of great si...
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.
Altered KSPG expression by keratocytes following corneal injury
Mol Vis, 2003
The corneal surface consists of a multi-layered (5-7 cell layers) non-keratinized, stratified squamous epithelium. In part the strength of the corneal epithelium is maintained by its tissue-specific expression of intermediate filaments consisting of paired K3/K12 keratins, which is a characteristic of corneal-type epithelial differentiation [1]. The next layer is the stroma that comprises 90% of the corneal thickness in humans and accounts for the major contribution towards corneal curvature and clarity, and refractive power. Collagen I, V, VI, and XII make up the majority of the stroma [2-5] along with the dermatan sulfate proteoglycan decorin [6], and the keratan sulfate proteoglycans (KSPG), e.g., lumican [7], keratocan [8], and osteoglycin/mimecan [9]. Large epithelial wounds and alkali burns often lead to poor visual outcome, including conjunctivalization, stromal scarring, recurrent epithelium erosions, vascularization, and limbal deficiency [10-17]. The resultant corneal stroma after wound healing is one of disorganized collagen fibrils and opacity. This outcome is significantly different from the uniform collagen fibril diameter and interfibrillar spacing allowing virtually unobscured light resonance resulting from corneal development [18]. The divergence of these two mechanisms suggests the involvement of other factors and/or a difference in gene expression during wound healing. Keratocytes are the major cell-type in the corneal stroma expressing the KSPGs and collagen [19-21] and MMPs for tissue remodeling during wound healing. One early event well documented is a population of keratocytes undergo apoptosis following a corneal wound [22-28]. It remains elusive whether the stromal cells repopulate the injured corneas maintain keratocyte phenotype. Previous reports demonstrate differences (inflammation, necrosis, ulceration, and scarring) in the wound healing process of various wound types, specifically noting a unique healing process for the alkali burn wound [29-33]. One possible explanation is the variation in cytokines and growth factors expressed after a specific wound type [31,34]. Potential source for the initial factors are the tear, the remaining keratocytes and epithelial cells [31-37]. These signaling molecules have the potential to recruit inflammatory cells, promote apoptosis, and contribute to changes of gene expression patterns accounting for opaque scar tissue formation [38-45]. The purpose of this study was to examine the expression of corneal KSPGs as an indication of keratocyte phenotype
2002
To characterize changes over time in the genomic expression profile of rat corneas after excimer laser photorefractive keratectomy (PRK), in an effort to better understand the cellular response to injury and the dynamic changes that occur in gene expression patterns as a wound heals. METHODS. The corneal gene expression profile of 1176 genes at 3 and 7 days after PRK was determined and compared with untreated corneal gene expression patterns by interrogating commercially available cDNA arrays with labeled target cDNA prepared from pooled total RNA harvested from the respective treatment group of adult male rats. The gene expression patterns were inferred based on the hybridization intensities of the probes on the cDNA arrays. The hybridization signals were globally normalized and filtered. The data were analyzed by using hierarchical and k-means clustering algorithms before and after normalization of variances.
Investigative Ophthalmology & Visual Science, 2003
PURPOSE. Incisional or ablation injury to the corneal stroma is repaired by deposition of a fibrotic tissue produced by activated keratocytes, whereas cells lost from the underlying stroma after epithelial abrasion are simply replaced by keratocyte replication without expression of fibrotic markers. The purpose of this study was to investigate mechanisms that determine this differential keratocyte response.
Scientific Reports
Proper wound healing is dynamic in order to maintain the corneal integrity and transparency. Impaired or delayed corneal epithelial wound healing is one of the most frequently observed ocular defect and difficult to treat. Cyclin dependen kinase (cdk), a known cell cycle regulator, required for proper proliferating and migration of cell. We therefore investigated the role of cell cycle regulator cdk10, member of cdk family and its functional association with transcriptional factor (ETS2) at active phase of corneal epithelial cell migration. Our data showed that cdk10 was associated with ETS2, while its expression was upregulated at the active phase (18 hours) of cell migration and gradually decrease as the wound was completely closed. Topical treatment with anti-cdk10 and ETS2 antibodies delayed the wound closure time at higest concentration (10 µg/ml) compared to control. Further, our results also showed increased mRNA expression of cdk10 and ETS2 at active phase of migration at approximately 2 fold. Collectively, our data reveals that cdk10 and ETS2 efficiently involved during corneal wound healing. Further studies are warranted to better understand the mechanism and safety of topical cdk10 and ETS2 proteins in corneal epithelial wound-healing and its potential role for human disease treatment. Corneal epithelial injuries and burns produce extensive damage to the ocular surface epithelium and may cause significant loss of function 1. A rapid and efficient healing from injuries and environmental damges is necessary to maintain the cornea barrier that is essential for appropriate vision 2. Delayed in corneal epithelial wounds healing occur in number of disease states, however, persistence of these wounds can lead to loss of vision and even perforation of the eye 3. The World Health Organization (WHO) was estimatated 710 corneal ulcers per 100 000 population every year in south east asia region 4. However, in Pakistan corneal injuries or trauma are the common cause of blindness after cataract but data available about injuries is limited and does not indicate the magnitude of the problem. Recently Baig R et al. reported 39.7% eye injuries among all ocular complaints at emergency department (ED) visits in a private tertiary care hospital Karachi Pakistan 5. In our region, it was also reported that the frequency of trauma was 66% while metallic particles and road accedents were the major cause of ocular injuries 6,7. To reduce the potential of these debilitating injury or wounds is to promote the epithelial migration and decrease the chances of ocular infection with limited toxicity. Treatments for non-healing corneal wounds are limited and no specific therapy available so far. Knowing proper cell cycle division mechanism and specifically with their regulators would thus help to development a new therapeutic tools which trigger or control cell migration and proliferation. A fundamental requirement for proper proliferating and migration of cell, is the
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.