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Histopathology of human ischemic retinopathies

Yang, Qian; (2021) Histopathology of human ischemic retinopathies. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Retinal ischemia is a key feature in sight threatening eye diseases such as retinopathy of prematurity (ROP) or diabetic retinopathy (DR). Whilst the longterm consequences of ROP and DR are well described, our understanding of the early pathobiological events is much less clear. In particular cellular changes during the early stages of these disease are poorly studied so far. Most of our current insights about the pathobiological events are derived from animal models, with little confirmation in humans. The aim of this thesis is therefore to fill this gap by carefully characterizing vascular features and cellular damage in post-mortem tissue from patients with early stages of ROP and DR. To better understand the early cellular events in ROP, post-mortem eyes from postnatal, premature infants were collected. Different vascular phenotypes could be distinguished in whole mount retinal vasculature stains. Differences in branching profiles and capillary free zone morphology implicated different levels of oxygen exposure in the infants studied. Furthermore, characterizing a hyperplastic ridge, distal to the edge of the growing vascular plexus, revealed a correlation between the retinal astrocyte marker PAX2 and increased expression of vascular endothelial growth factor (VEGF). This suggests that retinal astrocytes make an important, but so far overlooked, contribution to the pathology in ROP. To better understand early stages of DR, eyes from diabetic donors without diagnosed DR were collected. Whole mount imaging revealed an indistinguishable retinal vasculature phenotype compared to controls, confirming the absence of DR. However, detailed quantification of vessel profiles on retinal cross sections demonstrated a 5-fold increase in acellular (and presumed non-perfused) capillaries (7-fold in the deeper plexuses) in retinas from diabetics without DR. Interestingly, localized capillary dropout of individual capillaries in the deeper plexuses did not correlated with a reduction of cells in the vicinity of the non-perfused capillaries. Instead, there was a panretinal loss of cells in the inner nuclear layer (INL) in diabetic retina, suggesting an ischemia independent mechanism for INL cell loss in diabetic retina.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Histopathology of human ischemic retinopathies
Event: UCL (University College London)
Language: English
Additional information: Copyright © The Author 2021. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/10121581
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