Participación de las proneurotrofinas y sus receptores en la degeneración retiniana en modelos murinos de Retinosis Pigmentaria
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2021
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01/02/2021
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Universidad Complutense de Madrid
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Abstract
La Retinosis Pigmentaria (RP) es un término que engloba un grupo heterogéneo de distrofias hereditarias de la retina, para las que actualmente no existe una terapia efectiva. Existen más de 300 mutaciones en unos 60 genes relacionadas con RP; sin embargo, la mayoría de los casos, comparten una muerte patológica y progresiva de los fotorreceptores que se relaciona directamente con la pérdida de visión y conduce inexorablemente a la ceguera. Por esta razón, los tratamientos, independientes del tipo de mutación que subyace a la degeneración visual, pero capaces de proteger a los fotorreceptores del daño y de la pérdida de función, aunque sean solo remedios paliativos, son posibilidades terapéuticas atractivas que se están intentando desarrollar activamente. Aunque se han caracterizado varios mecanismos moleculares responsables de la muerte de los fotorreceptores en RP, el orden en el que actúan y su importancia relativa en el curso de la enfermedad están lejos de haber sido determinados. No obstante, resultados obtenidos en nuestro grupo, así como observaciones publicadas por otros laboratorios, indican la existencia de un fuerte componente inflamatorio en este tipo de patologías, lo que permite anticipar que el daño en la retina se ve acelerado por desequilibrios en dichos procesos inflamatorios. Las proneurotrofinas son las formas precursoras de las neurotrofinas. Aunque durante años se consideraron simples estados de transición en el proceso madurativo de las neurotrofinas, actualmente se sabe que son ligandos con actividad propia que inducen, generalmente, efectos biológicos opuestos a sus formas maduras, mediante la unión a complejos receptores también distintos. Así, mientras que las neurotrofinas están implicadas en la supervivencia y diferenciación neuronal, las proneurotrofinas desencadenan, generalmente, procesos de muerte celular...
Retinitis Pigmentosa (RP) is a term that encompasses a heterogeneous group of hereditary retinal dystrophy, for which there is currently no effective therapy. There are more than 300 mutations in about 60 RP-related genes; however, in most cases, they share a pathological and progressive death of photoreceptors that is directly related to vision loss and inexorably leads to blindness. For this reason, treatments, independent of the type of mutation underlying visual degeneration, but capable of protecting photoreceptors from damage and loss of function, even if they are only palliative remedies, are attractive therapeutic possibilities that are being actively attempted. Although several molecular mechanisms responsible for the death of photoreceptors in RP have been characterized, the order in which they act and their relative importance in the course of the disease are far from determined. However, results obtained in our group, as well as observations published by other laboratories, indicate the existence of a strong inflammatory component in this type of pathology, which allows to anticipate that damage in the retina is accelerated by imbalances in such inflammatory processes. Proneurotrophins are the precursor forms of neurotrophins. Although for years they were considered simple transition states in the maturation process of neurotrophins, they are currently known to be ligandos with their own activity that generally induce biological effects opposed to their mature forms, by binding to also different receptor complexes. Thus, while neurotrophins are involved in neuronal survival and differentiation, proneurotrophins generally trigger cell death processes...
Retinitis Pigmentosa (RP) is a term that encompasses a heterogeneous group of hereditary retinal dystrophy, for which there is currently no effective therapy. There are more than 300 mutations in about 60 RP-related genes; however, in most cases, they share a pathological and progressive death of photoreceptors that is directly related to vision loss and inexorably leads to blindness. For this reason, treatments, independent of the type of mutation underlying visual degeneration, but capable of protecting photoreceptors from damage and loss of function, even if they are only palliative remedies, are attractive therapeutic possibilities that are being actively attempted. Although several molecular mechanisms responsible for the death of photoreceptors in RP have been characterized, the order in which they act and their relative importance in the course of the disease are far from determined. However, results obtained in our group, as well as observations published by other laboratories, indicate the existence of a strong inflammatory component in this type of pathology, which allows to anticipate that damage in the retina is accelerated by imbalances in such inflammatory processes. Proneurotrophins are the precursor forms of neurotrophins. Although for years they were considered simple transition states in the maturation process of neurotrophins, they are currently known to be ligandos with their own activity that generally induce biological effects opposed to their mature forms, by binding to also different receptor complexes. Thus, while neurotrophins are involved in neuronal survival and differentiation, proneurotrophins generally trigger cell death processes...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Biológicas, leída el 01/02/2021