Publication: Estudio a corto y largo plazo de la melatonina y el 5-MCA-NAT como tratamiento en la hipertensión ocular y el glaucoma
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2016-08-18
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Universidad Complutense de Madrid
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Abstract
El glaucoma engloba una serie de enfermedades que se caracterizan por la pérdida progresiva de las células ganglionares de la retina y la neuropatía del nervio óptico, que desencadenan finalmente una ceguera irreversible. La elevación de la presión intraocular (PIO) aparece como el principal desencadenante de esta patología en la mayoría de los casos, ya que produce una disminución del flujo sanguíneo hacia la retina y un aumento del estrés oxidativo. La estrategia terapéutica más común implica el uso de fármacos hipotensores, a menudo combinados, asociados a efectos no deseados. En este marco, la melatonina y sus análogos, como el 5-MCA-NAT, surgen como alternativas a los fármacos ya existentes, por sus propiedades hipotensoras y antioxidantes y, en el caso del 5-MCA-NAT, por su posible acción a largo plazo. El objetivo de esta tesis es elucidar los mecanismos de la acción hipotensora aguda ya descrita para estos compuestos, determinando además el receptor y las vías de señalización implicadas en esta respuesta a corto plazo. En este mismo sentido nos proponemos confirmar la existencia de efectos hipotensores a largo plazo, analizando esta respuesta a diferentes fármacos y esclareciendo si ésta se debe a la capacidad de estos compuestos como modificadores de la expresión génica de enzimas o receptores implicados en la regulación de la PIO...
Glaucoma is the term applied to a group of eye diseases characterized by progressive loss of retinal ganglion cell and optic nerve neuropathy and eventually triggers irreversible blindness. The elevated intraocular pressure (IOP) appears as the main feature for this disease in most of the cases, since it produces a reduction of blood flow to the retina and increased oxidative stress. Consequently the most common therapeutic strategy is based on the use of antihypertensive drugs, often in combination, but unfortunatelly associated with undesirable effects. In this context, melatonin and its analogues, such as 5-MCA-NAT emerge as alternatives to the existing drugs, offering the advantage of hypotensive and antioxidant properties and in the case of 5-MCA-NAT, and providing potential long term action. The objective of this thesis is to elucidate the mechanisms of the acute hypotensive action, already described for these compounds and determining the receptor and signaling pathways involved in this short-term response. In addition we wish to confirm the existence of long term hypotensive effects, analyzing different drugs and clarifying whether this is a consequence of the ability of these compounds as modifiers of gene expression of enzymes or receptors involved in the regulation of IOP...
Glaucoma is the term applied to a group of eye diseases characterized by progressive loss of retinal ganglion cell and optic nerve neuropathy and eventually triggers irreversible blindness. The elevated intraocular pressure (IOP) appears as the main feature for this disease in most of the cases, since it produces a reduction of blood flow to the retina and increased oxidative stress. Consequently the most common therapeutic strategy is based on the use of antihypertensive drugs, often in combination, but unfortunatelly associated with undesirable effects. In this context, melatonin and its analogues, such as 5-MCA-NAT emerge as alternatives to the existing drugs, offering the advantage of hypotensive and antioxidant properties and in the case of 5-MCA-NAT, and providing potential long term action. The objective of this thesis is to elucidate the mechanisms of the acute hypotensive action, already described for these compounds and determining the receptor and signaling pathways involved in this short-term response. In addition we wish to confirm the existence of long term hypotensive effects, analyzing different drugs and clarifying whether this is a consequence of the ability of these compounds as modifiers of gene expression of enzymes or receptors involved in the regulation of IOP...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Veterinaria, Departamento de Bioquímica y Biología Molecular IV, leída el 21/01/2016. Tesis formato europeo (compendio de artículos)