Keratoconus is a progressive bilateral corneal protrusion that leads to irregular astigmatism and impairment of vision. Keratoconus is an etiologically heterogeneous corneal dystrophy and both environmental and genetic factors play a role in its etiopathogenesis. In this analytical review, we have studied all the genes that are structurally associated with keratoconus and have tried to explain the function of each gene and its association with other eye disorders in a concise way. In addition, using gene set enrichment analysis, it was attempted to find the most important impaired metabolic pathways in keratoconus. Several genetic studies have been carried out on keratoconus and several genes have been identified as risk factors involved in the etiology of the disease. In the current study, 16 studies, including nine association studies, five genome-wide association studies, one linkage study, and one meta-analysis, were reviewed and based on the 19 genes found, enrichment was performed and the most important metabolic pathways involved in the disease were identified. The enrichment results indicated that the two pathways, interleukin 1 processing and assembly of collagen fibrils, are significantly associated with the disease. Obviously, the results of this study, in addition to providing information about the genes involved in the disease, can provide an integrated insight into the gene-based etiology of keratoconus and therapeutic opportunities thereof. 相似文献
Telocytes (TC) are typically defined as cells with telopodes by their ultrastructural features. Their presence was reported in the interstitium of various organs in vertebrates, including humans. However, no study has yet described the presence of TC in the human eye and in particular, within the stromal compartment of the cornea. To address this issue, samples of normal and pathologic (keratoconic) human corneas were tested by immunohistochemistry for CD34, platelet‐derived growth factor receptor α (PDGFRα) and c‐kit/CD117 or examined by transmission electron microscopy. We found that TC coexpressing CD34 and PDGFRα were distributed throughout the whole normal corneal stroma with different TC subtypes being distinguishable on the basis of the expression of the stemness marker c‐kit (i.e. c‐kit‐positive and c‐kit‐negative TC subpopulations). Transmission electron microscopy examination confirmed the existence of spindle‐shaped and bipolar TC typically displaying two long and thin moniliform telopodes establishing intercellular contacts formed by gap junctions. Keratoconic corneas were characterized by ultrastructural damages and patchy loss of TC with an almost complete depletion of the c‐kit‐positive TC subpopulation. We propose that TC may contribute to the maintenance of corneal stromal homoeostasis and that, in particular, the c‐kit‐positive TC subtype might have stemness capacity participating in corneal regeneration and repair processes. Further studies are needed to clarify the differential roles of corneal TC subtypes as well as the possible therapeutic applications of TC in degenerative corneal disorders such as keratoconus. 相似文献
The aim of this study was to evaluate whether OCT topography of the Bowman's layer and artificial intelligence (AI) can result in better diagnosis of forme fruste (FFKC) and clinical keratoconus (KC). Normal (n = 221), FFKC (n = 72) and KC (n = 116) corneas were included. Some of the FFKC and KC patients had the fellow eye (VAE‐NT) with normal topography (n = 30). The Scheimpflug and OCT scans of the cornea were analyzed. The curvature and surface aberrations (ray tracing) of the anterior corneal surface [air‐epithelium (A‐E) interface in OCT] and epithelium‐Bowman's layer (E‐B) interface (in OCT only) were calculated. Four random forest models were constructed: (1) Scheimpflug only; (2) OCT A‐E only; (3) OCT E‐B only; (4) OCT A‐E and E‐B combined. For normal eyes, both Scheimpflug and OCT (A‐E and E‐B combined) performed equally in identifying these eyes (P = .23). However, OCT A‐E and E‐B showed that most VAE‐NT eyes were topographically similar to normal eyes and did not warrant a separate classification based on topography alone. For identifying FFKC eyes, OCT A‐E and E‐B combined performed significantly better than Scheimpflug (P = .006). For KC eyes, both Scheimpflug and OCT performed equally (P = 1.0). Thus, OCT Topography of Bowman's layer significantly improved the detection of FFKC eyes. 相似文献
The cornea is a transparent and avascular tissue that functions as the major refractive structure for the eye. A wide variety of growth factors, chemokines, cytokines and their receptors are synthesized by corneal epithelial and stromal cells, and are found in tears. These molecules function in corneal wound healing and in inflammatory responses. Proteoglycans and glycoproteins are essential for normal corneal function, both at the air-epithelial interface and within the extracellular matrix. The ocular MUC mucins may play roles in forming the mucus layer of the tear film, in regulating tear film spread, and in inhibiting the adhesion of pathogens to the ocular surface. Lumican, keratocan and mimecan are the major keratan sulfate proteoglycans of the corneal stroma. They are essential, along with other proteoglycans and interfibrillar proteins, including collagens type VI and XII, for the maintenance of corneal transparency. Corneal epithelial cells interact with a specialized extracellular matrix structure, the basement membrane, composed of a specific subset of collagen type IV and laminin isoforms in addition to ubiquitous extracellular matrix molecules. Matrix metalloprotein-ases have been identified in normal corneal tissue and cells and may play a role in the development of ulcerative corneal diseases. Changes in extracellular matrix molecule localization and synthesis have been noted in other types of corneal diseases as well, including bullous keratopathy and keratoconus. 相似文献
Keratoconus is an eye disorder that causes the cornea to take an abnormal conical shape, thus impairing its refractive functions and causing blindness. The late diagnosis of keratoconus is among the principal reasons for corneal surgical transplantation. This pathology is characterized by a reduced corneal stiffness in the region immediately below Bowman's membrane, probably due to a different lamellar organization, as suggested by previous studies. Here, the lamellar organization in this corneal region is characterized in three dimensions by means of second‐harmonic generation (SHG) microscopy. In particular, a method based on a three‐dimensional correlation analysis allows to probe the orientation of sutural lamellae close to the Bowman's membrane, finding statistical differences between healthy and keratoconic samples. This method is demonstrated also in combination with an epi‐detection scheme, paving the way for a potential clinical ophthalmic application of SHG microscopy for the early diagnosis of keratoconus.
SHG image acquired with sagittal optical sectioning ( A ) of a healthy cornea and ( B ) of a keratoconic cornea. Scale bars: 30 μm. 相似文献
Irregularity of the Bowman's layer (BL) in keratoconus (KC, sample size (n) = 28) and forme fruste keratoconus (FFKC, n = 18) eyes was evaluated. Subjects underwent high resolution OCT imaging (Bioptigen Inc., USA) and corneal tomography (Pentacam v1.20r41, OCULUS Optikgeräte GmbH, Germany). Anterior edge of the BL was segmented. A Bowman's roughness index (BRI) was defined as the sum of the enclosed areas between segmented edge and a smooth 3rd order polynomial fit to the edge. BRI was compared with corneal aberrations, Keratoconus percentage index (KISA), Cone location magnitude index (CLMI) and Belin–Ambrosio enhanced ectasia display overall deviation index (BAD‐D). Area under the curve (AUC) was determined with logistic regression (LR). Mean BRI (×10–3) was 2.12 mm2, 1.81 mm2 and 1.7 mm2 in normal (n = 26), FFKC and KC eyes, respectively (p < 0.001). BAD‐D (0.79) and BRI (0.74) had the best AUC for FFKC. By combining BAD‐D and BRI, the AUC improved to 0.85 (p = 0.01). For KC eyes, KISA (0.94), CLMI (0.88), BAD‐D (0.96) and aberrations had comparable AUC (p > 0.05). However, LR with BRI and other indices didn't improve the AUC in KC eyes (p > 0.05). BRI was significantly reduced in FFKC and KC eyes. It improved the detection of FFKC but not KC eyes.
The cornea’s mechanical response to intraocular pressure elevations may alter in ectatic diseases such as keratoconus. Regional variations of mechanical deformation in normal and keratoconus eyes during intraocular pressure elevation have not been well-characterized. We applied a high-frequency ultrasound elastography technique to characterize the regional deformation of normal and keratoconus human corneas through the full thickness of corneal stroma. A cross-section centered at the corneal apex in 11 normal and 2 keratoconus human donor eyes was imaged with high-frequency ultrasound during whole globe inflation from 5 to 30 mmHg. An ultrasound speckle tracking algorithm was used to compute local tissue displacements. Radial, tangential, and shear strains were mapped across the imaged cross-section. Strains in the central (1 mm surrounding apex) and paracentral (1 to 4 mm from apex) regions were analyzed in both normal and keratoconus eyes. Additional regional analysis was performed in the eye with severe keratoconus presenting significant thinning and scarring. Our results showed that in normal corneas, the central region had significantly smaller tangential stretch than the paracentral region, and that within the central region, the magnitudes of radial and shear strains were significantly larger than that of tangential strain. The eye with mild keratoconus had similar shear strain but substantially larger radial strains than normal corneas, while the eye with severe keratoconus had similar overall strains as in normal eyes but marked regional heterogeneity and large strains in the cone region. These findings suggested regional variation of mechanical responses to intraocular pressure elevation in both normal and keratoconus corneas, and keratoconus appeared to be associated with mechanical weakening in the cone region, especially in resisting radial compression. Comprehensive characterization of radial, tangential, and shear strains through corneal stroma may provide new insights to understand the biomechanical alterations in keratoconus. 相似文献
Myopia and keratoconus have become common corneal diseases that threaten the quality of human vision, and keratoconus is one of the most common indications for corneal transplantation worldwide. Collagen crosslinking (CXL) using riboflavin and ultraviolet A (UVA) light is an effective approach for treating ophthalmic disorders and has been shown clinically not only to arrest further progression of keratoconus but also to improve refractive power for cornea. However, CXL surgery irradiated by UVA has various potential risks such as surface damage and endothelial cell damage. Here, near-infrared femtosecond laser-based two-photon CXL was first applied to ex vivo human corneal stroma, operating at low photon energy with high precision and stability. After two-photon CXL, the corneal stiffness can be enhanced by 300% without significantly reducing corneal transparency. These findings illustrate the optimized direction that depositing high pulses energy in corneal focal volume (not exceeding damage threshold), and pave the way to 3D CXL of in vivo human cornea with higher safety, precision, and efficacy. 相似文献