Regulatory mechanisms of melatonin synthesis in the control of intraocular pressure

Ocular hypertension, although not considered a disease itself, it leads to glaucoma which eventually cause irreversible vision loss. Consequently, glaucoma therapeutic approach is to lower intraocular pressure (IOP). Nonetheless, anti-glaucoma drugs come often with several side effects that can lead...

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Detalhes bibliográficos
Autor: Awad Alkozi, Hanan
Tipo de documento: tese
Data de publicação:2018
País:España
Recursos:Universidad Complutense de Madrid (UCM)
Repositório:Docta Complutense
Idioma:inglês
OAI Identifier:oai:docta.ucm.es:20.500.14352/16213
Acesso em linha:https://hdl.handle.net/20.500.14352/16213
Access Level:Acceso aberto
Palavra-chave:612.842.6(043.2)
Intraocular pressure
Ocular hypertension
Endogenous melatonin
Aqueous humor
Presión intraocular
Hipertensión ocular
Melatonina endógena
Humor acuoso
Endocrinología
Oftalmología
3205.02 Endocrinología
3201.09 Oftalmología
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oai_identifier_str oai:docta.ucm.es:20.500.14352/16213
network_acronym_str ES
network_name_str España
repository_id_str
spelling Regulatory mechanisms of melatonin synthesis in the control of intraocular pressureMecanismos de regulación de la síntesis de la melatonina para el control de la presión intraocularAwad Alkozi, Hanan612.842.6(043.2)Intraocular pressureOcular hypertensionEndogenous melatoninAqueous humorPresión intraocularHipertensión ocularMelatonina endógenaHumor acuosoEndocrinologíaOftalmología3205.02 Endocrinología3201.09 OftalmologíaOcular hypertension, although not considered a disease itself, it leads to glaucoma which eventually cause irreversible vision loss. Consequently, glaucoma therapeutic approach is to lower intraocular pressure (IOP). Nonetheless, anti-glaucoma drugs come often with several side effects that can lead to treatment withdrawal in some cases. In this context, melatonin and its analogs emerges as potential complimentary/alternative treatment, offering the advantage of hypotensive and antioxidant properties. The present PhD thesis aim to investigate endogenous melatonin content in the aqueous humor and describes mechanisms involved in detecting increased IOP, along with a focus on the possibility of melatonin receptors to interact with different receptors with the intention to find a more effective combined therapeutical approach. Finally, to study the attribution of the crystalline lens to the aqueous humor melatonin content and to discover the regulation of its synthesis in this ocular structure. Results showed a correlation between melatonin levels in the aqueous humor and IOP. Melatonin levels were found higher in patients with elevated IOP. Using a glaucomatous animal model (DBA/2J) it was possible to corroborate our findings. In vitro assays pointed to the participation of the TRPV4 channel, which is sensitive to pressure, among other stimuli. Activation of the mentioned channel in human immortalised nonpigmented ciliary body epithelial cells resulted in an increment of melatonin secretion through the increase of aralkylamine N-acetyltransferase (AANAT) expression, the first enzyme in melatonin synthesis. In addition, short term assays showed that the TRPV4 activation leaded to AANAT phosphorylation through a cascade of intracellular events that involves the participation of calmodulin and calcium-calmodulin dependent protein kinase II. This phosphorylation activates AANAT and therefore melatonin synthesis is stimulated...Universidad Complutense de MadridPintor Just, JesúsPérez de Lara, María JesúsUniversidad Complutense de Madrid20182018-09-2420182018-09-24doctoral thesishttp://purl.org/coar/resource_type/c_db06info:eu-repo/semantics/doctoralThesisapplication/pdfhttps://hdl.handle.net/20.500.14352/16213reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/162132026-06-02T12:44:21Z
dc.title.none.fl_str_mv Regulatory mechanisms of melatonin synthesis in the control of intraocular pressure
Mecanismos de regulación de la síntesis de la melatonina para el control de la presión intraocular
title Regulatory mechanisms of melatonin synthesis in the control of intraocular pressure
spellingShingle Regulatory mechanisms of melatonin synthesis in the control of intraocular pressure
Awad Alkozi, Hanan
612.842.6(043.2)
Intraocular pressure
Ocular hypertension
Endogenous melatonin
Aqueous humor
Presión intraocular
Hipertensión ocular
Melatonina endógena
Humor acuoso
Endocrinología
Oftalmología
3205.02 Endocrinología
3201.09 Oftalmología
title_short Regulatory mechanisms of melatonin synthesis in the control of intraocular pressure
title_full Regulatory mechanisms of melatonin synthesis in the control of intraocular pressure
title_fullStr Regulatory mechanisms of melatonin synthesis in the control of intraocular pressure
title_full_unstemmed Regulatory mechanisms of melatonin synthesis in the control of intraocular pressure
title_sort Regulatory mechanisms of melatonin synthesis in the control of intraocular pressure
dc.creator.none.fl_str_mv Awad Alkozi, Hanan
author Awad Alkozi, Hanan
author_facet Awad Alkozi, Hanan
author_role author
dc.contributor.none.fl_str_mv Pintor Just, Jesús
Pérez de Lara, María Jesús
Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 612.842.6(043.2)
Intraocular pressure
Ocular hypertension
Endogenous melatonin
Aqueous humor
Presión intraocular
Hipertensión ocular
Melatonina endógena
Humor acuoso
Endocrinología
Oftalmología
3205.02 Endocrinología
3201.09 Oftalmología
topic 612.842.6(043.2)
Intraocular pressure
Ocular hypertension
Endogenous melatonin
Aqueous humor
Presión intraocular
Hipertensión ocular
Melatonina endógena
Humor acuoso
Endocrinología
Oftalmología
3205.02 Endocrinología
3201.09 Oftalmología
description Ocular hypertension, although not considered a disease itself, it leads to glaucoma which eventually cause irreversible vision loss. Consequently, glaucoma therapeutic approach is to lower intraocular pressure (IOP). Nonetheless, anti-glaucoma drugs come often with several side effects that can lead to treatment withdrawal in some cases. In this context, melatonin and its analogs emerges as potential complimentary/alternative treatment, offering the advantage of hypotensive and antioxidant properties. The present PhD thesis aim to investigate endogenous melatonin content in the aqueous humor and describes mechanisms involved in detecting increased IOP, along with a focus on the possibility of melatonin receptors to interact with different receptors with the intention to find a more effective combined therapeutical approach. Finally, to study the attribution of the crystalline lens to the aqueous humor melatonin content and to discover the regulation of its synthesis in this ocular structure. Results showed a correlation between melatonin levels in the aqueous humor and IOP. Melatonin levels were found higher in patients with elevated IOP. Using a glaucomatous animal model (DBA/2J) it was possible to corroborate our findings. In vitro assays pointed to the participation of the TRPV4 channel, which is sensitive to pressure, among other stimuli. Activation of the mentioned channel in human immortalised nonpigmented ciliary body epithelial cells resulted in an increment of melatonin secretion through the increase of aralkylamine N-acetyltransferase (AANAT) expression, the first enzyme in melatonin synthesis. In addition, short term assays showed that the TRPV4 activation leaded to AANAT phosphorylation through a cascade of intracellular events that involves the participation of calmodulin and calcium-calmodulin dependent protein kinase II. This phosphorylation activates AANAT and therefore melatonin synthesis is stimulated...
publishDate 2018
dc.date.none.fl_str_mv 2018
2018-09-24
2018
2018-09-24
dc.type.none.fl_str_mv doctoral thesis
http://purl.org/coar/resource_type/c_db06
dc.type.openaire.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/16213
url https://hdl.handle.net/20.500.14352/16213
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidad Complutense de Madrid
publisher.none.fl_str_mv Universidad Complutense de Madrid
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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