Publication: Diseño y evaluación de sistemas microparticulares biodegradables de agentes neuroprotectores para el tratamiento de patologías neurodegenerativas oculares|
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2018-01-11
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Universidad Complutense de Madrid
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Abstract
Las enfermedades neurodegenerativas que afectan al segmento posterior del ojo se caracterizan por ser devastadoras. En su mayoría son crónicas y pueden cursar con un daño progresivo del nervio óptico y la pérdida de células ganglionares de la retina (CGR), fotorreceptores y otras células de la retina ocasionando la pérdida de visión. Una de las estrategias terapéuticas encaminadas al tratamiento de estas patologías es la neuroprotección, que se centra en prevenir, limitar, y en algunos casos revertir, la degeneración o muerte de las células neuronales. En el caso de la neuroprotección ocular, una aproximación terapéutica consiste en la administración de factores neurotróficos exógenos encargados de modular el crecimiento, la diferenciación, la reparación y la supervivencia de las neuronas gracias a su unión a receptores específicos. Estos factores engloban una amplia variedad de sustancias entre las cuales cabe destacar el Factor Neurotrófico Derivado de la Glía (GDNF), cuyo efecto neuroprotector ha sido demostrado en diversas patologías oculares. También existen otras moléculas terapéuticas que ejercen efecto neuroprotector a nivel ocular mediante mecanismos de acción diferentes a los factores neurotróficos. Un ejemplo son los antioxidantes que se destinan a paliar el daño oxidativo que acompaña a las patologías retinianas. En este sentido, la melatonina juega un papel importante ya que presenta un potente carácter antioxidante, atenuando el daño celular causado por los radicales libres tanto en las CGR como en los fotorreceptores. En esta misma línea, la administración de vitaminas antioxidantes se plantea de igual modo como una alternativa terapéutica encaminada a contrarrestar el daño oxidativo. Concretamente, la vitamina E (VitE) ha demostrado actividad en diferentes enfermedades de la retina en las que se produce, entre otros, estrés oxidativo...
Neurodegenerative diseases that affect the posterior segment of the eye are characterised by being devastating in nature. The majority of them are chronic and they may involve gradual damage to the optic nerve and loss of retinal ganglion cells (RGCs), photoreceptors and other cells in the retina, thereby causing loss of vision. One therapeutic strategy intended to treat these diseases is neuroprotection, which focuses on preventing, limiting and in some cases reversing the degeneration and death of neuronal cells. In the case of ocular neuroprotection, one therapeutic approach consists of administering exogenous neurotrophic factors responsible for modulating the growth, differentiation, repair and survival of neurons through their binding to specific receptors. These factors encompass a wide variety of substances including glial cell line-derived neurotrophic factor (GDNF), whose neuroprotective effect has been demonstrated in various eye diseases. Other therapeutic molecules also exert a neuroprotective effect on the eye through different mechanisms of action than neurotrophic factors. One example is antioxidants intended to palliate the oxidative damage that accompanies retinal diseases. In this regard, melatonin plays a significant role since it has strong antioxidant properties whereby it attenuates the cell damage caused by free radicals in both RGCs and photoreceptors. Likewise, the administration of antioxidant vitamins has been proposed as a therapeutic alternative intended to counteract oxidative damage. Specifically, vitamin E (VitE) has demonstrated activity in different diseases of the retina with oxidative stress, among other features. However, as this type of disease is multifactorial, the search for new therapeutic strategies is focused on combination treatment, for which various active substances are used depending on the patient's therapeutic requirements...
Neurodegenerative diseases that affect the posterior segment of the eye are characterised by being devastating in nature. The majority of them are chronic and they may involve gradual damage to the optic nerve and loss of retinal ganglion cells (RGCs), photoreceptors and other cells in the retina, thereby causing loss of vision. One therapeutic strategy intended to treat these diseases is neuroprotection, which focuses on preventing, limiting and in some cases reversing the degeneration and death of neuronal cells. In the case of ocular neuroprotection, one therapeutic approach consists of administering exogenous neurotrophic factors responsible for modulating the growth, differentiation, repair and survival of neurons through their binding to specific receptors. These factors encompass a wide variety of substances including glial cell line-derived neurotrophic factor (GDNF), whose neuroprotective effect has been demonstrated in various eye diseases. Other therapeutic molecules also exert a neuroprotective effect on the eye through different mechanisms of action than neurotrophic factors. One example is antioxidants intended to palliate the oxidative damage that accompanies retinal diseases. In this regard, melatonin plays a significant role since it has strong antioxidant properties whereby it attenuates the cell damage caused by free radicals in both RGCs and photoreceptors. Likewise, the administration of antioxidant vitamins has been proposed as a therapeutic alternative intended to counteract oxidative damage. Specifically, vitamin E (VitE) has demonstrated activity in different diseases of the retina with oxidative stress, among other features. However, as this type of disease is multifactorial, the search for new therapeutic strategies is focused on combination treatment, for which various active substances are used depending on the patient's therapeutic requirements...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Farmacia, Departamento de Farmacia y Tecnología Farmacéutica, leída el 15/06/2017