Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.601656
Title: Mechanisms controlling vascular tone in the retina
Author: Hinds , Kevin
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2013
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Abstract:
This thesis has investigated some of the cellular and sub-cellular mechanisms involved in three of the major blood flow autoregulation pathways of the retina, including pressure-autoregulation, regulation according to endothelium-derived factors. and neurovascular coupling. Myogenic responses represent the changes in vascular tone evoked by alterations in intra• luminal pressure, and they are mediated by vascular smooth muscle cell (VSMC) stretch and de polarisation. KCI evoked depolarisation of the VSMC of isolated retinal arterioles was used to investigate the changes to sub•cellular Ca2+ signaling underlying this pathway. Depolarisation triggers an increase in [Ca2+]i in VSMC mediated by voltage-sensitive L-type Ca2+ channels, and a subsequent stimulation of Ca2+ release from the sarcoplasmic reticulum via ryanodine sensitive (RyR) channels - which manifests as an increase in the frequency of spontaneous Ca2+ oscillations. The application of the endothelial-derived endothelin-l (Et-l) to isolated retinal arterioles caused elevations in both Ca2+ oscillations and sparks, as well as an increase in VSMC [Ca2+Ji. This reaction was mediated by an activation of EtAR on the VSMC plasma membrane and a stimulation of phospholipase C. This causes the production of inositol triphosphate (IP3). which activates Ca2+ release from the SR via IP3R. It was also found that RyR channels were also activated by Et-l, suggesting IP3R-RyR crosstalk. Retinal wholemount preparations were also employed to investigate the role of the neurotransmitter GABA in mediating vascular responses. The application of high concentrations of GABA evoked predominately vasodilation responses, mediated by GABAB receptors. It was also shown that GABA appears to make some contribution to baseline vascular tone, as the application of GABA receptor antagonists to un-constricted vessels evoked vasoconstrictions. Immunohistochemistry studies have indicated that GABAA and GABAB receptors are expressed on Muller cells, which have been linked to neurovascular coupling in the past suggesting a possible pathway for this vascular reaction.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.601656  DOI: Not available
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