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...
| Autor: | |
|---|---|
| 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 |
| Resumo: | 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... |
|---|