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From micro to nanostructure: an investigation into the connective tissue of the ageing human optic nerve head

Paletto, Laura 2019. From micro to nanostructure: an investigation into the connective tissue of the ageing human optic nerve head. PhD Thesis, Cardiff University.
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The purpose of this thesis was to investigate the micro- and nanostructural changes of the optic nerve head (ONH) regions, namely lamina cribrosa (LC), peripapillary sclera (ppsclera) and region of insertion (RoIns) as a function of age and glaucoma. The microstructure of ageing and glaucomatous ONHs have been explored following nonlinear microscopy [two-photon excited fluorescence (TPEF) and second harmonic generation (SHG)]. Small-angle (SAXS) and wide-angle (WAXS) X-ray diffraction have been used to explore into the nanoarchitecture of collagen and elastic fibre in the ageing ONH. X-ray microtomography (XMT) was used to assess microstructural changes of the ONH in age and glaucoma. Micro- and nanomechanics have been explored following Brillouin microscopy and the combination of SAXS/WAXS, respectively. In the ageing ppsclera, collagen crimp period increased from 19.64 ± 6.41 µm at the age 2 to 22.04 ± 10 µm at the age of 88 years (p=0.004). Elastic fibre content significantly increased from 0% in the 2 years old up to 29% in the 88 years old (p=0.003) in the LC and from 0% up to 49% (p=0.019) in the region of insertion. Significant increase in collagen fibril diameter [from 98.98 nm ± 0.9 at 22 years old to 113.01 nm ± 1.5 at the age of 85 (p=0.026)] and intermolecular Bragg spacing [from 1.44 nm ± 0.12 to 1.53 nm ± 0.32 (p=0.022)] were found along with a decreased interfibrillar spacing [from 37.63 nm ± 7.22 to 12.6 nm ± 4.54 (p=0.003)]. Collagen crimp significantly increased in the LC and region of insertion in moderate (p=0.013, p=0.013) and advanced (p=0.021, p=0.033) glaucoma. XMT enabled the discrimination of the connective tissue from the surrounding neuronal pores and 3D reconstruction of XMT dataset showed altered LC and pore shape in glaucomatous ONH. In conclusion, changes in the connective tissue of the ageing and glaucomatous ONH at both micro- and nanostructure aided in a better understanding on how the ONH responds to intraocular pressure elevation.

Item Type: Thesis (PhD)
Date Type: Acceptance
Status: Unpublished
Schools: Optometry and Vision Sciences
Subjects: R Medicine > RE Ophthalmology
Uncontrolled Keywords: glaucoma, lamina cribrosa, optic nerve head, connective tissue, collagen, elastic fibre
Date of First Compliant Deposit: 4 December 2020
Date of Acceptance: 6 September 2019
Last Modified: 17 Jun 2021 02:05

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