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Three-dimensional studies of the developing mammalian cornea.

Feneck, Eleanor Mai 2019. Three-dimensional studies of the developing mammalian cornea. PhD Thesis, Cardiff University.
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Abstract

This thesis aimed to understand the structural changes that occur during the development of the mammalian cornea. The imaging techniques used included novel three-dimensional serial block-face scanning electron microscopy, transmission electron microscopy, optical coherence tomography, X-ray diffraction and immunofluorescence. These techniques were utilised to investigate the human, mouse and the fibrillin-1 knockout mouse cornea. The mouse cornea had no collagenous primary stroma to direct mesenchymal cell migration. Stromal cell projections associated with adjacent corneal stromal cells and the corneal epithelium, and appeared to direct collagen alignment. The mouse stroma expressed types I, II and V collagen, and later type IX collagen in the epithelium. Proteoglycans were observed before collagen deposition in the mouse stroma, associated with stromal cells and collagen fibrils. A collagenous primary stroma was identified in the human embryonic cornea prior to mesenchymal cell migration. The corneal endothelium contained novel cell extensions that associated with the mesenchymal cells and the acellular collagenous matrix; these results suggested that the endothelium assists mesenchymal cell migration. The human adult cornea contained true elastic fibres in the peripheral posterior cornea with fibrillin-rich microfibrils in the central posterior cornea. The elastic fibres in the mouse contained only fibrillin-rich microfibrils. In the human, elastic fibres were detected from week 12 of development and had a distribution similar to the mature human cornea. This included elastic fibre sheets directly anterior to the endothelium and individual elastic fibres in the posterior peripheral stroma. The fibrillin-1 knockout mouse cornea had reduced stromal thickness and a disorganised extracellular matrix. It is thought that elevated transforming growth factor-beta disrupted the corneal architecture. This thesis has contributed novel findings of the events that develop the mammalian cornea. The results identified fundamental differences and similarities between the mouse and human models and have suggested new mechanisms in the developmental process.

Item Type: Thesis (PhD)
Date Type: Completion
Status: Unpublished
Schools: Optometry and Vision Sciences
Subjects: R Medicine > RE Ophthalmology
Uncontrolled Keywords: Cornea, Development, Elastic Fibres, Electron Microscopy, Primary Stroma, Marfan Syndrome.
Date of First Compliant Deposit: 16 January 2020
Last Modified: 16 Jan 2020 11:38
URI: http://orca-mwe.cf.ac.uk/id/eprint/128421

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