Connective tissue structure of the ocular tunic and its targeted modification in novel treatments

Ma, Qian 2025. Connective tissue structure of the ocular tunic and its targeted modification in novel treatments. PhD Thesis, Cardiff University. Item availability restricted.

	PDF - Accepted Post-Print Version Restricted to Repository staff only until 6 August 2026 due to copyright restrictions. Download (3MB)
	PDF (Cardiff University Electronic Theses and Dissertations Publication Form) - Supplemental Material Restricted to Repository staff only Download (139kB)

Abstract

The cornea and sclera, the outermost fibrous layers of the eye, consist mainly of collagen and serve distinct functions due to differences in fibril organisation. Corneal fibrils are uniform and regularly spaced, ensuring transparency, while scleral fibrils are irregular, providing biomechanical resistance to intraocular pressure and protection for internal structures. Together, they cooperatively determine eye shape and thereby refractive status. Changes in their ultrastructure are linked to conditions including corneal opacity and myopia. This thesis explores emerging therapies targeting these conditions and their effects on corneal and scleral ultrastructure. Research techniques used include small-angle and wide-angle x-ray scattering (for fibrillar and molecular collagen structure), transmission electron microscopy with cuprolinic blue (direct observation of collagen and proteoglycans), tensile testing (measurement of tissue stiffness), and multiphoton microscopy (second harmonic generation for collagen fibres, twophoton microscopy for elastin). In a rat wound model induced by irregular phototherapeutic keratectomy, intrastromal injection of corneal stromal keratocytes, corneal stromal stem cells, and umbilical cord mesenchymal stem cells restored corneal transparency. Corneal stromal keratocytes showed the most effective therapeutic results, with almost complete restoration of stromal collagen structure, proteoglycans, and trace element wound marker profiles. Additionally, two scleral crosslinking methods, glyceraldehyde and bacteriochlorophyll-derivative WST11 (with near-infrared (NIR) light activation), both increased scleral stiffness, but had distinctly different ultrastructural effects. The results suggest that glyceraldehyde-induced collagen crosslinking occurs at both the intermolecular and interfibrillar level, whereas WST11/NIRinduced crosslinking predominantly occurs at the supra-molecular level. Possible mechanisms are presented and discussed in relation to therapeutic potential. This thesis provides valuable insights into how various emerging therapies alter corneal and scleral ultrastructure. The results contribute to our understanding of how therapeutic interventions act by modifying the ultrastructure of the ocular tunic, offering promising avenues for treating conditions such as corneal opacity and myopia.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Schools > Optometry and Vision Sciences
Subjects:	R Medicine > RE Ophthalmology
Uncontrolled Keywords:	Corneal opacities, myopia, scleral crosslinking, glyceraldehyde, WST11/NIR, collagen, x-ray scattering, transmission electron microscopy, tensile testing, multiphoton microscopy.
Date of First Compliant Deposit:	6 August 2025
Last Modified:	06 Aug 2025 10:08
URI:	https://orca.cardiff.ac.uk/id/eprint/180276

Actions (repository staff only)

Edit Item