Abstract
As the outer lens in the eye, the cornea needs to be strong and transparent. These properties are governed by the arrangement of the constituent collagen fibrils, but the mechanisms of how this develops in mammals is unknown. Using novel 3-dimensional scanning and conventional transmission electron microscopy, we investigated the developing mouse cornea, focusing on the invading cells, the extracellular matrix and the collagen types deposited at different stages. Unlike the well-studied chick, the mouse cornea had no acellular primary stroma. Collagen fibrils initially deposited at E13 from the presumptive corneal stromal cells, become organised into fibril bundles orthogonally arranged between cells. Extensive cell projections branched to adjacent stromal cells and interacted with the basal lamina and collagen fibrils. Types I, II and V collagen were expressed from E12 posterior to the surface ectoderm, and became widespread from E14. Type IX collagen localised to the corneal epithelium at E14. Type VII collagen, the main constituent of anchoring filaments, was localised posterior to the basal lamina. We conclude that the cells that develop the mouse cornea do not require a primary stroma for cell migration. The cells have an elaborate communication system which we hypothesise helps cells to align collagen fibrils.
Highlights
The cornea’s biomechanical strength and optical transparency are governed by the ability of collagen fibrils to assemble into organised lamellae, under the influence of proteoglycans controlling collagen fibril diameter and biosynthesis[1,2]
Utilising three-dimensional electron microscopy techniques to image the structural development of the prenatal mouse cornea from E10-E18, this study identified extensive cell extensions within the developing mammalian corneal stroma that spanned adjacent cells and showed a strong tendency to align with the direction of collagen fibrils
This paper demonstrated the presence of types I, II and V collagen posterior to the surface ectoderm from E12 which spread across the developing corneal stroma by E14, initially being synthesised in the anterior stroma
Summary
The cornea’s biomechanical strength and optical transparency are governed by the ability of collagen fibrils to assemble into organised lamellae, under the influence of proteoglycans controlling collagen fibril diameter and biosynthesis[1,2]. Type IX collagen breakdown activates the swelling of the primary stroma, initiating the migration of mesenchymal cells[7,8]. The identification of the collagen types and extracellular matrix interactions within avian development has led to a greater understanding of the developmental events and the components required to achieve avian corneal transparency. Studies that have analysed collagen fibril assembly within prenatal tendon development have identified collagen being transported from the Golgi apparatus into fibripositors that deposit and align collagen fibrils[14,15,16,17] This theory of collagen fibril deposition has been suggested to occur during avian corneal development[16], but has not been seen in the mammalian cornea. Elucidating the mechanisms underlying the somewhat different collagen arrangement in the mammalian cornea will lead to a greater understanding of how the mammalian cornea achieves transparency through development, and why there seem to be similarities, but some fundamental differences, between the avian and mammalian cornea
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