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br Introduction Our ability to see our surrounding relies di
Introduction
Our ability to see our surrounding relies directly on the integrity of the anatomical structures composing our eyes. One of these key components is the cornea, consisting of the outer layer of the eye. Its transparency is crucial for light transmission to the retina and allows proper visual perception of our environment. However, because of its location, the cornea is subjected to chemical and mechanical injuries. Corneal wounds are often the result of abrasion caused by fingernails [1] or prolonged contact lenses wear [2]. However, chemical burns, which can extensively damage the eye surface, remain the more severe cause of corneal wounds. Burn severity depends greatly on the nature of the chemical substance [3]. Contact with the limbal area is also a key factor of the injury’s severity, the prognostic of healing being poor when more than 50% of the limbal area is damaged [4]. The consequences of such corneal damages are dramatic and can lead to the complete loss of vision. Infections causing ulceration are frequent after corneal injuries [5]. If not treated rapidly and properly, the infectious pathogen can penetrate the entire cornea and cause damages to the subjacent tissues [6]. Many of these injuries will compel to corneal transplant or eye enucleation when they are untreated [7]. Furthermore, the loss of stem 64c receptor from the limbus of the damaged eye can lead to the limbal stem cell deficiency syndrome that also causes a partial or complete opacification of the cornea [8]. In the more severe cases, a complete loss of vision may arise [9]. Regardless of the cause, the faster wound closure is occurring following corneal injury, the fewer consequences will result.
Recent improvements in tissue engineering have led to the reconstruction of a functional human corneal substitute that mimics the native cornea. This tridimensional substitute is composed of both a stroma and a stratified epithelium made up of 5–7 layers of untransformed human corneal epithelial cells (HCECs) [10], [11], [12]. More recently, this 3D-model was completed by the addition of a monolayer of corneal endothelial cells [11]. This novel corneal substitute relies on the ability of fibroblasts to secrete their own extracellular matrix (ECM) when ascorbic acid is added to the culture media, described as the self-assembly approach [13]. Because it is devoid of any synthetic material, our human tissue-engineered corneas (hTECs) share many aspects with the native cornea, such as a well-organized basement membrane (BM) and a typical epithelial stratification [11], [12]. Recently, this substitute has been used in our laboratory to study both the cellular and molecular processes occurring during wound healing [14]. The dynamics of wound closure were found to be very similar between our hTEC and the native cornea, as the same genes and enzymes (in this case, matrix metalloproteinases) were found to be similarly altered during this process [15]. Because of these similarities, our hTEC represents an outstanding model that we can exploit to study in detail the molecular mechanisms of corneal wound healing as a prerequisite to further studies in animals.
Corneal wound healing is a complex event involving many processes such as cell death, proliferation, migration, adhesion and differentiation [16]. During these steps, the composition of the ECM is continually modified to allow proper reepithelialization, epithelial cell migration and differentiation [17], [18]. The ECM is a non-cellular network of proteins and polysaccharides on which cells adhere through cell-matrix interactions [19]. Changes in the composition of the ECM are perceived by the integrins, a family of membrane-anchored receptors that bind components of the ECM [20], [21]. The downstream cascades of mediators activated by these cell-matrix interactions then lead to the transcription of genes involved in wound healing [22]. The major pathways activated by the integrins include the JAK/STAT [23], MAPK [24] and PI3K/AKT pathways [25], [26]. However, in corneal wound healing, little is known about which pathway contributes the most to the healing process.