Publication: Papel biológico del diadenosin tetrafosfato en el ojo: efecto sobre la composición lacrimal e implicación en la función de barrera corneal
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2016-08-03
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Universidad Complutense de Madrid
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Abstract
El Ap4A es una molécula con un amplio papel biológico en el ojo. Se ha descrito su implicación en procesos de secreción lagrimal, cicatrización epitelial, regulación de la presión intraocular, y presenta también un papel neuroprotector sobre los terminales simpáticos que inervan el cuerpo ciliar. El objetivo de este trabajo ha sido analizar la participación del Ap4A en otras posibles funciones a nivel ocular. En concreto se ha estudiado la capacidad de este dinucléotido para estimular la liberación de proteínas lagrimales de acción antibacteriana tales como la lisozima y la lactoferrina. Por otra parte se ha investigado su efecto como modulador de la función de barrera de la córnea a través de la regulación de los niveles de expresión de proteínas constituyentes de las tight junctions (TJ). Dicho efecto sobre la barrera puede tener una importante repercusión en la entrada de fármacos y en la consiguiente eficacia terapéutica de los mismos. Por último, se ha estudiado la posible implicación del dinucleótido en el proceso de edematización descrito en modelos animales glaucomatosos tales como el ratón DBA/2J. Con el objetivo de averiguar si la activación de Ap4A inducía un efecto sobre la producción de dos proteínas antimicrobianas relevantes de la lágrima (lisozima y lactoferrina) se realizaron ensayos en la lágrima de conejos albinos de Nueva Zelanda, mediante las técnicas de agar-agar y ELISA. Los resultados obtenidos demostraron que Ap4A produce un aumento en la concentración de lisozima y de lactoferrina del 93% y 24%, respectivamente, frente a valores basales, y este efecto está mediado por receptores de tipo P2...
Ap4A is a molecule with a wide biological role in the eye. It is involved in processes such as tear secretion, epithelial healing, intraocular pressure regulation, and it has a neuroprotective role on the sympathetic nerve terminals that innervate the ciliary body. The aim of this work has been to analyze Ap4A participation in other possible functions in the eye. Particularly, Ap4A ability to stimulate the release of some bactericidal tear proteins, such as lysozyme and lactoferrin has been studied. Also, its effect as a modulator in the corneal barrier function through the regulation of tight junctions (TJ) protein levels has been analyzed. This effect on the corneal barrier may have a significant impact on the delivery of drugs and in their consequent therapeutic efficacy. Finally, the possible involvement of the dinucleotide in the corneal edema process described in glaucomatous animal models such as the DBA/2J mouse has been investigated too. In order to know if the Ap4A activation induced an effect on the bactericidal production of two relevant antimicrobial tear proteins (lysozyme and lactoferrin), assays have been conducted using the tears of New Zealand white rabbits, by means of agar-agar and ELISA techniques. The results obtained showed that Ap4A produced an increase in the concentration of lysozyme and lactoferrin (93% and 24%, respectively) compared to baseline, effects mediated by P2 receptors. Considering the antibacterial action exerted by these proteins, these results suggest that topical application of Ap4A would contribute to reinforce the protection against potential infections of the ocular surface..
Ap4A is a molecule with a wide biological role in the eye. It is involved in processes such as tear secretion, epithelial healing, intraocular pressure regulation, and it has a neuroprotective role on the sympathetic nerve terminals that innervate the ciliary body. The aim of this work has been to analyze Ap4A participation in other possible functions in the eye. Particularly, Ap4A ability to stimulate the release of some bactericidal tear proteins, such as lysozyme and lactoferrin has been studied. Also, its effect as a modulator in the corneal barrier function through the regulation of tight junctions (TJ) protein levels has been analyzed. This effect on the corneal barrier may have a significant impact on the delivery of drugs and in their consequent therapeutic efficacy. Finally, the possible involvement of the dinucleotide in the corneal edema process described in glaucomatous animal models such as the DBA/2J mouse has been investigated too. In order to know if the Ap4A activation induced an effect on the bactericidal production of two relevant antimicrobial tear proteins (lysozyme and lactoferrin), assays have been conducted using the tears of New Zealand white rabbits, by means of agar-agar and ELISA techniques. The results obtained showed that Ap4A produced an increase in the concentration of lysozyme and lactoferrin (93% and 24%, respectively) compared to baseline, effects mediated by P2 receptors. Considering the antibacterial action exerted by these proteins, these results suggest that topical application of Ap4A would contribute to reinforce the protection against potential infections of the ocular surface..
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Óptica y Optometría, Departamento de Bioquímica y Biología Molecular IV, leída el 19-01-2016