Corneal structure and transparency Meek, Keith M.; Knupp, Carlo
Progress in retinal and eye research,
11/2015, Letnik:
49
Journal Article
Recenzirano
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The corneal stroma plays several pivotal roles within the eye. Optically, it is the main refracting lens and thus has to combine almost perfect transmission of visible light with precise shape, in ...order to focus incoming light. Furthermore, mechanically it has to be extremely tough to protect the inner contents of the eye. These functions are governed by its structure at all hierarchical levels. The basic principles of corneal structure and transparency have been known for some time, but in recent years X-ray scattering and other methods have revealed that the details of this structure are far more complex than previously thought and that the intricacy of the arrangement of the collagenous lamellae provides the shape and the mechanical properties of the tissue. At the molecular level, modern technologies and theoretical modelling have started to explain exactly how the collagen fibrils are arranged within the stromal lamellae and how proteoglycans maintain this ultrastructure. In this review we describe the current state of knowledge about the three-dimensional stromal architecture at the microscopic level, and about the control mechanisms at the nanoscopic level that lead to optical transparency.
•We are coming close to understanding how its complex structure governs the shape and biomechanical behaviour of the cornea.•Transparency arises from the arrangement of collagen fibrils and the presence of crystallins within the stromal cells.•Fibril positions at any instant are maintained by the arrangement of proteoglycans around and between them.•Transparency loss in pathology or following surgery can arise from a combination of many different structural alterations.
The bulk of the corneal stroma is comprised of a layered network of fibrillar collagen. Determining the architecture of this unique structure may help us to better understand the cornea's ...biomechanical and optical function. The analysis of diffraction patterns obtained when X-rays are passed through the regularly arranged collagen molecules and fibrils of the stromal matrix yields quantitative data on fibrillar organisation, including the orientation and distribution of collagen lamellae within the corneal plane. In recent years, by exploiting the radiation from powerful synchrotron sources, techniques have been developed to enable the mapping of collagen fibril, and therefore lamellar, directions across whole corneas. This article aims to summarise the use of X-ray diffraction to map the orientation and distribution of collagen in the corneal stroma. The implications of the knowledge gained so far are discussed in relation to the optical and biomechanical properties of the cornea, and their alteration due to disease and surgical intervention.
Fibrillin-1 is a pivotal structural component of the kidney's glomerulus and peritubular tissue. Mutations in the fibrillin-1 gene result in Marfan syndrome (MFS), an autosomal dominant disease of ...the connective tissue. Although the kidney is not considered a classically affected organ in MFS, several case reports describe glomerular disease in patients. Therefore, this study aimed to characterize the kidney in the mgΔlpn-mouse model of MFS. Affected animals presented a significant reduction of glomerulus, glomerulus-capillary, and urinary space, and a significant reduction of fibrillin-1 and fibronectin in the glomerulus. Transmission electron microscopy and 3D-ultrastructure analysis revealed decreased amounts of microfibrils which also appeared fragmented in the MFS mice. Increased collagen fibers types I and III, MMP-9, and α-actin were also observed in affected animals, suggesting a tissue-remodeling process in the kidney. Video microscopy analysis showed an increase of microvessel distribution coupled with reduction of blood-flow velocity, while ultrasound flow analysis revealed significantly lower blood flow in the kidney artery and vein of the MFS mice. The structural and hemodynamic changes of the kidney indicate the presence of kidney remodeling and vascular resistance in this MFS model. Both processes are associated with hypertension which is expected to worsen the cardiovascular phenotype in MFS.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
4.
Corneal cross-linking - a review Meek, Keith M; Hayes, Sally
Ophthalmic & physiological optics,
03/2013, Letnik:
33, Številka:
2
Journal Article
Recenzirano
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Purpose
To review cross‐linking the cornea using riboflavin and ultraviolet A light, which has been widely adopted, refined and applied in a range of corneal surgeries and pathologies where the ...strength of the cornea might be compromised.
Recent findings
A large number of clinical trials have been carried out, most of which have demonstrated that standard cross‐linking is a successful method to halt the progression of keratoconus or even aid regression.
Summary
This review describes our current understanding of the technique, focussing on how cross‐linking works, how the treatment is being optimised, the clinical results that have been reported to date and the potential use of the therapy in the treatment of other corneal disorders.
To examine the effect of riboflavin/UVA corneal crosslinking on stromal ultrastructure and hydrodynamic behaviour.
One hundred and seventeen enucleated ungulate eyes (112 pig and 5 sheep) and 3 pairs ...of rabbit eyes, with corneal epithelium removed, were divided into four treatment groups: Group 1 (28 pig, 2 sheep and 3 rabbits) were untreated; Group 2 (24 pig) were exposed to UVA light (3.04 mW/cm(2)) for 30 minutes and Group 3 (29 pig) and Group 4 (31 pig, 3 sheep and 3 rabbits) had riboflavin eye drops applied to the corneal surface every 5 minutes for 35 minutes. Five minutes after the initial riboflavin instillation, the corneas in Group 4 experienced a 30 minute exposure to UVA light (3.04 mW/cm(2)). X-ray scattering was used to obtain measurements of collagen interfibrillar spacing, spatial order, fibril diameter, D-periodicity and intermolecular spacing throughout the whole tissue thickness and as a function of tissue depth in the treated and untreated corneas. The effect of each treatment on the hydrodynamic behaviour of the cornea (its ability to swell in saline solution) and its resistance to enzymatic digestion were assessed using in vitro laboratory techniques.
Corneal thickness decreased significantly following riboflavin application (p<0.01) and also to a lesser extent after UVA exposure (p<0.05). With the exception of the spatial order factor, which was higher in Group 4 than Group 1 (p<0.01), all other measured collagen parameters were unaltered by cross-linking, even within the most anterior 300 microns of the cornea. The cross-linking treatment had no effect on the hydrodynamic behaviour of the cornea but did cause a significant increase in its resistance to enzymatic digestion.
It seems likely that cross-links formed during riboflavin/UVA therapy occur predominantly at the collagen fibril surface and in the protein network surrounding the collagen.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To investigate the initial events in the development of the human cornea, focusing on cell migration, and extracellular matrix synthesis and organization. To determine whether elastic fibers are ...present in the extracellular matrix during early human corneal development.
Human corneas were collected from week 7 to week 17 of development. An elastic fiber-enhancing stain, tannic acid-uranyl acetate, was applied to all tissue. Three-dimensional serial block-face scanning electron microscopy combined with conventional transmission electron microscopy was used to analyze the corneal stroma.
An acellular collagenous primary stroma with an orthogonal arrangement of fibrils was identified in the central cornea from week 7 of corneal development. At week 7.5, mesenchymal cells migrated toward the central cornea and associated with the acellular collagenous matrix. Novel cell extensions from the endothelium were identified. Elastic fibers were found concentrated in the posterior peripheral corneal stroma from week 12 of corneal development.
This study provides novel evidence of an acellular primary stroma in the early development of the embryonic human cornea. Cell extensions exist as part of a communication system and are hypothesized to assist in the migration of the mesenchymal cells and the development of the mature cornea. Elastic fibers identified in early corneal development may play an important role in establishing corneal shape.
The posterior sclera has a major biomechanical influence on the optic nerve head, and may therefore be important in glaucoma. Scleral material properties are influenced significantly by collagen ...fiber architecture. Here we quantitatively map fiber orientation in non-glaucoma and glaucoma posterior human sclerae.
Wide-angle x-ray scattering quantified fiber orientation at 0.5-mm intervals across seven non-glaucoma post-mortem human sclerae, and five sclerae with glaucoma history and confirmed axon loss. Multiphoton microscopy provided semiquantitative depth-profiling in the peripapillary sclera.
Midposterior fiber orientation was either uniaxial (one preferred direction) or biaxial (two directions). The peripapillary sclera was characterized by a ring of fibers located mainly in the mid-/outer stromal depth and encompassing ∼50% of the total tissue thickness. Fiber anisotropy was 37% higher in the peripapillary sclera compared with midposterior, varied up to 4-fold with position around the scleral canal, and was consistently lowest in the superior-nasal quadrant. Mean fiber anisotropy was significantly lower in the superior-temporal (P < 0.01) and inferior-nasal (P < 0.05) peripapillary scleral quadrants in glaucoma compared with non-glaucoma eyes.
The collagen fiber architecture of the posterior human sclera is highly anisotropic and inhomogeneous. Regional differences in peripapillary fiber anisotropy between non-glaucoma and glaucoma eyes may represent adaptive changes in response to elevated IOP and/or glaucoma, or baseline structural properties that associate with predisposition to glaucomatous axon damage. Quantitative fiber orientation data will benefit numerical eye models aimed at predicting the sclera's influence on nerve head biomechanics, and thereby its possible role in glaucoma.
This article investigates in vitro light transmission through the human cornea in the ultraviolet (UV) portion of the electromagnetic spectrum as a function of position across the cornea from center ...to periphery. Spectrophotometry was used to measure UV transmission in the wavelength range 310–400 nm, from the central cornea to its periphery. UV transmission decreases away from the center, and this is attributed to scattering and absorbance. Corneal endothelial cells, which line the back of the cornea and are more numerous in the periphery, therefore receive a lower dose of UV than do those in the central cornea. This is consistent with the recent observation that endothelial cells in the corneal periphery exhibit less nuclear oxidative DNA damage than those in the central cornea.
Riboflavin‐5‐phosphate (RF) is the most commonly used photosensitizer in corneal cross‐linking (CXL), but its hydrophilicity and negative charge limit its penetration through the corneal epithelium ...into the stroma. To enhance the corneal permeability of RF and promote its efficacy in the treatment of keratoconus, novel hibiscus‐like RF@ZIF‐8 microsphere composites 6RF@ZIF‐8 NF (nanoflake) are prepared using ZIF‐8 nanomaterials as carriers, which are characterized by their hydrophobicity, positive potential, biocompatibility, high loading capacities, and large surface areas. Both hematoxylin and eosin endothelial staining and TUNEL assays demonstrate excellent biocompatibility of 6RF@ZIF‐8 NF. In in vivo studies, the 6RF@ZIF‐8 NF displayed excellent corneal permeation, and outstanding transepithelial CXL (TE‐CXL) efficacy, slightly better than the conventional CXL protocol. Furthermore, the special hibiscus‐like structures of 6RF@ZIF‐8 NF meant that it has better TE‐CXL efficacy than that of 6RF@ZIF‐8 NP (nanoparticles) due to the larger contact area with the epithelium and the shorter RF release passage. These results suggest that the 6RF@ZIF‐8 NF are promising for transepithelial corneal cross‐linking, avoiding the need for epithelial debridement.
Novel engineering hydrangea‐like RF@ZIF‐8 microsphere composites with outstanding trans‐epithelial corneal cross‐linking (TE‐CXL) efficacy are prepared using one pot methods. The obtained biocompatible composites display excellent tolerance, remarkable corneal permeation, improved CXL efficacy than conventional CXL protocol without corneal epithelium debridement, suggesting a promising nanomedicine for corneal cross‐linking.
An experimental study has been conducted to determine the stress–strain behaviour of human corneal tissue and how the behaviour varies with age. Fifty-seven well-preserved ex vivo donor corneas aged ...between 30 and 99 years were subjected to cycles of posterior pressure up to 60 mm Hg while monitoring their behaviour. The corneas were mechanically clamped along their ring of scleral tissue and kept in physiological conditions of temperature and hydration. The tissue demonstrated hyper-elastic pressure-deformation and stress–strain behaviour that closely matched an exponential trend. Clear stiffening (increased resistance to deformation) with age was observed in all loading cycles, and the rate of stiffness growth was nonlinear with bias towards older specimens. With a strong statistical association between stiffness and age (p < 0.05), it was possible to develop generic stress–strain equations that were suitable for all ages between 30 and 99 years. These equations, which closely matched the experimental results, depicted corneal stiffening with age in a form suitable for implementation in numerical simulations of ocular biomechanical behaviour.
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