Development of the corneal stroma, and the collagen–proteoglycan associations that help define its structure and function

Quantock, Andrew J.; Young, Robert D.

doi:10.1002/dvdy.21579

Cited by 110 publications

(87 citation statements)

References 110 publications

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“…This is somewhat surprising, bearing in mind that stromal keratocytes have rounded morphology at day 10, when a large proportion of the extracellular space is occupied by hyaluronate-rich fluid (37). Presumptive keratocytes, which early in corneal embryogenesis invade the primary stroma (38), are key to the formation of a mature and functional cornea. The fate of the loose orthogonally arranged collagen bundles of the primary stroma remains poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Three-dimensional aspects of matrix assembly by cells in the developing cornea

Young

Knupp

Pinali

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Cell-directed deposition of aligned collagen fibrils during corneal embryogenesis is poorly understood, despite the fact that it is the basis for the formation of a corneal stroma that must be transparent to visible light and biomechanically stable. Previous studies of the structural development of the specialized matrix in the cornea have been restricted to examinations of tissue sections by conventional light or electron microscopy. Here, we use volume scanning electron microscopy, with sequential removal of ultrathin surface tissue sections achieved either by ablation with a focused ion beam or by serial block face diamond knife microtomy, to examine the microanatomy of the cornea in three dimensions and in large tissue volumes. The results show that corneal keratocytes occupy a significantly greater tissue volume than was previously thought, and there is a clear orthogonality in cell and matrix organization, quantifiable by Fourier analysis. Three-dimensional reconstructions reveal actin-associated tubular cell protrusions, reminiscent of filopodia, but extending more than 30 μm into the extracellular space. The highly extended network of these membrane-bound structures mirrors the alignment of collagen bundles and emergent lamellae and, we propose, plays a fundamental role in dictating the orientation of collagen in the developing cornea.C onnective tissues fulfill diverse functions but conform to a general structural plan of cells surrounded by an extracellular matrix in which collagen is the main structural element (1, 2). Composition and tissue-specific organization of the component collagen fibrils are considered to be critically important for the functional properties of any particular tissue. The unique transparent quality of the cornea arises from its remarkably ordered architecture of aligned and regularly spaced fibrils with a small, consistent diameter (∼30 nm), which are arranged, not into fibers or fascicles as in most other tissues but in superimposed, flattened layers, or lamellae. Lamellae and their component collagen fibrils exhibit preferential orientations throughout the corneal thickness (3), which appear to be closely related to the biomechanical loads to which the tissue is subjected. In adult vertebrates, lamellae traverse the full diameter of the cornea for most of its thickness, and in the avian eye-the subject of most developmental studies-undergo a gradual rotation in their orientation with depth (4). Individual collagen fibrils within midstromal lamellae also appear to traverse the entire diameter of the cornea, a distance of ∼11 mm in adult human eyes. The extraordinary level of order in matrix organization within a hierarchy of fibril, lamella, and stroma overall appears to reflect a considerable level of regulatory influence presumably involving both cell activity and intermolecular interactions.Collagen fibrils exhibit a microfibrillar substructure (5-7), undergoing self-assembly spontaneously in vitro from soluble monomeric collagen in a process largely dependent upon the phy...

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Section: Discussionmentioning

confidence: 99%

Three-dimensional aspects of matrix assembly by cells in the developing cornea

Young

Knupp

Pinali

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Collagen is the primary constituent of the stromal matrix and include collagen types I, V, VI, VIII, XII, XIII and XIV (Quantock and Young 2008). The major collagen of the stroma is collagen type I and it forms heterotypic fibrils with collagen type V (Birk et al 1988).…”

Section: Constituents Of Corneal Stromal Ecmmentioning

confidence: 99%

The integrin needle in the stromal haystack: emerging role in corneal physiology and pathology

Parapuram

Hodge

2014

J. Cell Commun. Signal.

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Several studies have established the role of activated corneal keratocytes in the fibrosis of the cornea. However, the role of keratocytes in maintaining the structural integrity of a normal cornea is less appreciated. We focus on the probable functions of integrins in the eye and of the importance of integrin-mediated keratocyte interactions with stromal matrix in the maintenance of corneal integrity. We point out that further understanding of how keratocytes interact with their matrix could establish a novel direction in preventing corneal pathology including loss of structural integrity as in keratoconus or as in fibrosis of the corneal stroma.Keywords Cornea . Keratocytes . Corneal stroma . Extracellular matrix . Integrins . KeratoconusThe simple cellular organization of the cornea is belied by its fascinating specialization for transparency. The cornea has three main tissue layers, the outer epithelium, the stroma in the middle and the inner endothelial layer. The stromal connective tissue, the layer mainly responsible for the corneal configuration, constituting nearly 80 % of the thickness of the cornea, is extremely resilient, capable of resisting intraocular pressure and protecting the posterior structures of the eye. The stromal tissue consists of lamellae of orthogonally arranged collagen fibrils surrounded by proteoglycans; in between the lamellae of collagen are found the keratocytes. The nearorderly arrangement of collagen lamellae, the narrow diameter of the collagen fibrils, regular interfibrillar space, associated proteoglycans and the expression of crystalline proteins in the keratocytes (Birk 2001;Kao and Liu 2002;Jester et al. 2007; Hassell and Birk 2010) are some of the main factors responsible for corneal transparency. Consequently, the factors affecting corneal transparency such as fibrotic changes due to disease or injury are problems primarily associated with the stroma. Thus it is important to achieve further understanding of the mechanisms by which the stroma acquires and maintains its structural integrity and its transparency.

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“…The proteoglycans surrounding the fibrils are major constituents of the interfibrillar space, and these undergo several changes during development that have been correlated with fibrillar compaction (Quantock and Young 2008). Furthermore, their absence in knock-out mouse corneas is accompanied by a loss of fibril order (Chakravarti et al 1988;Meek et al 2003b).…”

Section: Regulators Of Fibril Diameter and Spacingmentioning

confidence: 99%

Corneal collagen—its role in maintaining corneal shape and transparency

2009

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Corneal collagen has a number of properties that allow it to fulfil its role as the main structural component within the tissue. Fibrils are narrow, uniform in diameter and precisely organised. These properties are vital to maintain transparency and to provide the biomechanical prerequisites necessary to sustain shape and provide strength. This review describes the structure and arrangement of corneal collagen from the nanoscopic to the macroscopic level, and how this relates to the maintenance of the form and transparency of the cornea.

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Development of the corneal stroma, and the collagen–proteoglycan associations that help define its structure and function

Cited by 110 publications

References 110 publications

Three-dimensional aspects of matrix assembly by cells in the developing cornea

Three-dimensional aspects of matrix assembly by cells in the developing cornea

The integrin needle in the stromal haystack: emerging role in corneal physiology and pathology

Corneal collagen—its role in maintaining corneal shape and transparency

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