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Anatomy of the cornea. (a) Section of the anterior part of the eye; (b) Section of the cornea illustrating six layers; (c) In vivo confocal microscopy image of the corneal endothelium. Courtesy of Geir A. Qvale.
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Corneal endothelium is a single layer of specialized cells that lines the posterior surface of cornea and maintains corneal hydration and corneal transparency essential for vision. Currently, transplantation is the only therapeutic option for diseases affecting the corneal endothelium. Transplantation of corneal endothelium, called endothelial kera...
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Corneal endothelial cells (CECs) are essential for maintaining corneal stromal hydration and ensuring its transparency, which is necessary for normal vision. Dysfunction of CECs leads to stromal decompensation, loss of transparency and corneal blindness. Corneal endothelium has low proliferative potential compared to surface epithelial cells leadin...
The corneal endothelium is a simple layer of epithelial cells strategically positioned at the posterior surface of the cornea. As the anatomic and physiologic boundary between the nutrient-rich aqueous humor and the avascular collag-enous stroma, the endothelium plays essential roles in tissue nourishment and transparency by balancing the influx an...
Citations
... CEC expansion is a crucial aspect of DMEK, necessitating innovative approaches to enhance cell proliferation and preserve cellular function in vitro. Mechanical and biophysical stimuli represent promising strategies to modulate CEC behavior and facilitate cell expansion for transplantation 87,[99][100][101][102][103][104] . Given that the corneal endothelium is constantly subjected to mechanical forces within the eye, which influence cellular behavior and function, replicating these physiological cues in culture can enhance CEC growth, morphology, and phenotype, ultimately improving transplant success. ...
Corneal diseases are the third leading cause of blindness worldwide. Descemet’s Membrane Endothelial Keratoplasty (DMEK) is the preferred surgical technique for treating corneal endothelial disorders, relying heavily on high-quality donor tissue. However, the scarcity of suitable donor tissue and the sensitivity of endothelial cells remain significant challenges. This review explores the current state of DMEK, focusing on advancements in tissue engineering as a promising solution to improve outcomes and address donor limitations.
... CEC expansion is a crucial aspect of DMEK, necessitating innovative approaches to enhance cell proliferation and preserve cellular function in vitro. Mechanical and biophysical stimuli represent promising strategies to modulate CEC behavior and facilitate cell expansion for transplantation [83][84][85][86][87][88][89]. Given that the corneal endothelium is constantly subjected to mechanical forces within the eye, which influence cellular behavior and function, replicating these physiological cues in culture can enhance CEC growth, morphology, and phenotype, ultimately enhancing transplant success. ...
Corneal diseases are the third leading cause of blindness worldwide. There are numerous causes of corneal blindness, and the common treatment for this condition often involves corneal tissue transplantation, such as Descemet's Membrane Endothelial Keratoplasty (DMEK). DMEK has been established as the preferred surgical technique for the treatment of corneal endothelial disorders. The success of DMEK depends largely on the quality of the donor endothelial cells and the trans-plantation procedure. However, the scarcity of suitable donor tissue and the sensitivity of endo-thelial cells pose a major challenge. In recent years, tissue engineering has attracted attention as potential solutions to these problems. This review offers an outline of the current landscape of DMEK in the context of bioengineering, exploring various methodologies, advancements, and fu-ture prospects.
... Silk fibroin is another promising biomaterial for the production of corneal scaffolds [6]: It is non-immunogenic and allows for easy production of high-resolution patterns via lithographic techniques [36]. In order to improve the structural integrity of the silk-based scaffolds, their cell adhesion/proliferation, and cell migration, several studies managed to blend fibroin-based scaffolds with several other biomaterials, including arginyl-glycylaspartic acid (RGD) peptide [86], poly-D-lysine (PDL) [87], aloe vera [88], β-carotene [89], lysophosphatidic acid [90], chitosan [91], and collagen obtaining significant results [48]. These characteristics make silk fibroin an ideal material to use as a substrate for the construction of the cornea and other tissues [36]. ...
The inner structures of the eye are protected by the cornea, which is a transparent membrane exposed to the external environment and subjected to the risk of lesions and diseases, sometimes resulting in impaired vision and blindness. Several eye pathologies can be treated with a keratoplasty, a surgical procedure aimed at replacing the cornea with tissues from human donors. Even though the success rate is high (up to 90% for the first graft in low-risk patients at 5-year follow-up), this approach is limited by the insufficient number of donors and several clinically relevant drawbacks. Alternatively, keratoprosthesis can be applied in an attempt to restore minimal functions of the cornea: For this reason, it is used only for high-risk patients. Recently, many biomaterials of both natural and synthetic origin have been developed as corneal substitutes to restore and replace diseased or injured corneas in low-risk patients. After illustrating the traditional clinical approaches, the present paper aims to review the most innovative solutions that have been recently proposed to regenerate the cornea, avoiding the use of donor tissues. Finally, innovative approaches to biological tissue 3D printing and xenotransplantation will be mentioned.
... A wide variety of carriers have already been considered, i.e., amniotic membrane [15], natural polymers (collagen I and IV, fibronectin, gelatin, laminin, the combination of laminin and chondroitin sulfate or fibronectin, collagen, and albumin) [16], silk fibroin [17], the posterior layer of human corneas not suitable for conventional grafts [18], or the anterior part of the human crystalline lens capsule [19]. They have been tested, mostly in vitro and less frequently in in vivo animal models [10]. ...
The bioengineering of corneal endothelial grafts consists of seeding in vitro cultured corneal endothelial cells onto a thin, transparent, biocompatible, and sufficiently robust carrier which can withstand surgical manipulations. This is one of the most realistic alternatives to donor corneas, which are in chronic global shortage. The anterior capsule of the crystalline lens has already been identified as one of the best possible carriers, but its challenging manual preparation has limited its use. In this study, we describe a femtosecond laser cutting process of the anterior capsule of whole lenses in order to obtain capsule discs of 8 mm diameter, similar to conventional endothelial grafts. Circular marks made on the periphery of the disc indicate its orientation. Immersion in water for 3 days is sufficient to completely remove the lens epithelial cells and to enable the seeding of corneal endothelial cells, which remain viable after 27 days of culture. Therefore, this method provides a transparent, decellularized disc ready to form viable tissue engineered endothelial grafts.
... The human cornea is a transparent avascular tissue, a multi-layered component of the ocular surface. It has a crucial role in the transmission and the focus of light onto the lens, where it is transmitted towards the retina [1][2][3]. It is an essential structure for vision, and damage to the cornea can lead to vision loss. ...
Background
The cornea, a vital component of the human eye, plays a crucial role in maintaining visual clarity. Understanding its ultrastructural organization and cell distribution is fundamental for elucidating corneal physiology and pathology. This study comprehensively examines the microarchitecture of the hydrated human cornea using contrast-enhanced micro-computed tomography (micro-CT).
Method
Fresh human corneal specimens were carefully prepared and hydrated to mimic their in vivo state. Contrast enhancement with Lugol's iodine-enabled high-resolution Micro-CT imaging. The cells' three-dimensional (3D) distribution within the cornea was reconstructed and analyzed.
Results
The micro-CT imaging revealed exquisite details of the corneal ultrastructure, including the spatial arrangement of cells throughout its depth. This novel approach allowed for the visualization of cells' density and distribution in different corneal layers. Notably, our findings highlighted variations in cell distribution between non-hydrated and hydrated corneas.
Conclusions
This study demonstrates the potential of contrast-enhanced micro-CT as a valuable tool for non-destructive, 3D visualization and quantitative analysis of cell distribution in hydrated human corneas. These insights contribute to a better understanding of corneal physiology and may have implications for research in corneal diseases and tissue engineering.
... Фи зиологической нормой считается потеря примерно 0,6% клеток за год жизни. При падении плотности эндотелиальных клеток роговицы ниже критиче ского порога, который составляет приблизительно 500 клеток/мм 2 , эндотелий утрачивает способность регулировать гидратацию стромы роговицы, что приводит к помутнению роговицы, и как следствие, снижению остроты зрения [3]. ...
Background . According to the World Health Organization, corneal diseases are one of the major causes of blindness globally. Endothelial dystrophy is one of the etiological factors leading to corneal diseases. The corneal endothelium is a monolayer of cells with virtually no mitotic activity. When the density of corneal endothelial cells falls below a critical threshold, the endothelium loses its ability to regulate corneal stromal hydration. This leads to corneal clouding and, consequently, to reduced visual acuity and quality of life of the patient. In this regard, various keratoplasty methods are widely used in clinical practice. Today, it is technically possible to transplant all corneal layers via penetrating keratoplasty, and to transplant the posterior epithelium via layer-bylayer keratoplasty. These surgical approaches are now widely used in everyday practice, but they require the use of scarce material – cadaveric donor corneas, from which grafts for the above-mentioned operations are formed in the conditions of an eye bank. In this regard, protocols for obtaining human corneal endothelial cell (HCEC) culture for subsequent transplantation have been proposed in recent years. However, the use of such approaches in Russia is limited by the law. The aim of this study was to experimentally justify the possibility of transplanting uncultured endothelial cells, isolated from cadaveric human corneas. Materials and methods . The first stage of the work consisted of obtaining a suspension of endothelial cells from cadaveric donor corneas and studying it; at the second stage, the transplantation effectiveness of the resulting cell suspension was assessed in an ex vivo experiment. Results . The cell phenotype after transplantation by the proposed method had high viability and preservation. Conclusions . The presented results suggest that phenotype and adhesion ability are preserved, and that the cell suspension has a high level of viability under adequate loss of endothelial cells during transplantation in the ex vivo experiment.
... The cornea is a highly transparent tissue located in the anterior segment of the eye, and it is responsible for more than 65% of its total optical power [1]. The external layer of the cornea, the corneal epithelium, is continuously replaced by stem cells located in a special niche called the limbus [2]. ...
The corneal epithelial layer is continuously replaced by limbal stem cells. Reconstructing this layer in vitro using synthetic scaffolds is highly needed. Poly-lactic-co-glycolic acid (PLGA) is approved for human use due to its biocompatibility and biodegradability. However, PLGA is hydrophobic, preventing cell adherence to PLGA membranes. PLGA scaffolds were prepared by electrospinning on a custom-made target drum spinning at a rate of 1000 rpm with a flow rate of 0.5 mL/h and voltage at 20 kV, then treated with oxygen plasma at 30 mA using a vacuum coater. Scaffolds were characterized by SEM, mechanically by tensile testing, and thermally by DSC and TGA. In vitro degradation was measured by weight loss and pH drop. Wettability was assessed through water uptake and contact angles measurements. Human limbal stem cells (hLSCs) were isolated and seeded on the scaffolds. Cell attachment and cytotoxicity assay were evaluated on day 1 and 5 after cell seeding. SEM showed regular fiber morphology with diameters ranging between 150 nm and 950 nm. Tensile strength demonstrated similar average stress values for both plasma- and non-plasma-treated samples. Scaffolds also showed gradual degradability over a period of 7–8 weeks. Water contact angle and water absorption were significantly enhanced for plasma-treated scaffolds, indicating a favorable increase in their hydrophilicity. Scaffolds have also supported hLSCs growth and attachment with no signs of cytotoxicity. We have characterized a nanofiber electrospun plasma-treated PLGA scaffold to investigate the mechanical and biological properties and the ability to support the attachment and maintenance of hLSCs.
... lial cell sheet transplantation or through cell injection into the anterior chamber. For the endothelial cell sheet transplantation, two main techniques have been proposed: primary hCEC isolated from cadaver donor corneas or differentiated stem cells and cell lines [112]. In the case of primary hCEC taken from human cadaveric donors, it has been noted that many donor factors have a significant impact on the culture success rate, such as cell density [113], cause of death, previous surgery in the eye, overall health, tissue storage time [114,115], age (with a lower proliferation capacity seen in older donors) [116], and the region of the cornea where hCEC belongs (with cells from the periphery having a higher proliferative capacity) [115,116]. ...
... This delivery can be achieved through endothelial cell sheet transplantation or through cell injection into the anterior chamber. For the endothelial cell sheet transplantation, two main techniques have been proposed: primary hCEC isolated from cadaver donor corneas or differentiated stem cells and cell lines [112]. In the case of primary hCEC taken from human cadaveric donors, it has been noted that many donor factors have a significant impact on the culture success rate, such as cell density [113], cause of death, previous surgery in the eye, overall health, tissue storage time [114,115], age (with a lower proliferation capacity seen in older donors) [116], and the region of the cornea where hCEC belongs (with cells from the periphery having a higher proliferative capacity) [115,116]. ...
The ocular surface is a complex structure that includes cornea, conjunctiva, limbus, and tear film, and is critical for maintaining visual function. When the ocular-surface integrity is altered by a disease, conventional therapies usually rely on topical drops or tissue replacement with more invasive procedures, such as corneal transplants. However, in the last years, regeneration therapies have emerged as a promising approach to repair the damaged ocular surface by stimulating cell proliferation and restoring the eye homeostasis and function. This article reviews the different strategies employed in ocular-surface regeneration, including cell-based therapies, growth-factor-based therapies, and tissue-engineering approaches. Dry eye and neurotrophic keratopathy diseases can be treated with nerve-growth factors to stimulate the limbal stem-cell proliferation and the corneal nerve regeneration, whereas conjunctival autograft or amniotic membrane are used in subjects with corneal limbus dysfunction, such as limbal stem-cell deficiency or pterygium. Further, new therapies are available for patients with corneal endothelium diseases to promote the expansion and migration of cells without the need of corneal keratoplasty. Finally, gene therapy is a promising new frontier of regeneration medicine that can modify the gene expression and, potentially, restore the corneal transparency by reducing fibrosis and neovascularization, as well as by stimulating stem-cell proliferation and tissue regeneration.
... The human cornea is a transparent avascular tissue, a multi-layered component of the ocular surface. It has a crucial role in the transmission and the focus of light onto the lens, where it is transmitted towards the retina [1][2][3]. It is an essential structure for vision, and damage to the cornea can lead to vision loss. ...
... It is also one of the most extremely innervated and sensitive tissues in the body, it is known that the density of nerve endings of corneal tissue about 300-400 times greater compared to the skin. Due to numerous nerve density in the cornea, the corneal diseases may be painful [7][8][9][10][11]. The cornea is composed of cellular and acellular components. ...
... However, a new cornea layer, Dua's layer, has been also described recently. Each of these layers has its own role in order to maintain normal visual function [2,3,[9][10][11]. In this paper, we reviewed the development, structure, function and physiological features of corneal epithelium, Bowman layer, corneal stroma, Dua's layer, Descemet's membrane and corneal endothelium from a new perspective. ...
... However, a new cornea layer, Dua's layer, has been also described recently. Each of these layers has its own role in order to maintain normal visual function [2,3,[9][10][11]. ...
The cornea has important functions such as protecting the structures within the globe, contributing to the refractive power of the eye, and focusing the light rays on the retina with minimum scattering. Although the neurobiological complexity of the retina and the dynamic movement of the lens are absent in the cornea, it is one of the most critical components of the perfect visual system, thanks to its transparency. In order to provide sustainable transparency in the cornea, which is very important for visual function, it is possible with the intense metabolic activity in the cornea and the perfect operation of the balanced ion liquid pump. The cornea provides excellent vision thanks to the structure and functions necessary for its unique function to continue regularly. This review focuses on cornea and tear film structure and physiology.
