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Renata Sarno y el monocromatismo de conos azules

 

Vía Nature
Vía Nature

La estrella de este post se llama Renata Sarno, porque ella ha sido la responsable de que me interesara por este tema tan concreto y empezara a investigar. Y todo porque una compañera del trabajo me pasó un artículo de las noticias de Nature de septiembre de 2014 acerca de las salidas no académicas de la investigación (aquí lo puedes leer, en inglés), en el que precisamente Renata Sarno es una de las tres personas protagonistas. Una física teórica que, al no encontrar oportunidades de financiación durante su postdoc (entre otras cosas por discriminación de género), decidió fundar la empresa Venere en pleno surgimiento de Internet. Pero en el artículo se resalta que Renata Sarno no ha abandonado del todo la investigación, ya que puso en marcha una fundación para investigar en monocromatismo de conos azules, una enfermedad rara que padecen miembros de su familia. Puedes consultar la página de la fundación BCM Families aquí.

¿En qué consiste el monocromatismo de conos azules? Para explicarlo, primero daremos unas breves pinceladas acerca del sistema de visión en color de los humanos, que depende de tres tipos de fotorreceptores llamados conos. Los conos rojos son tienen su máxima sensibilidad a la longitud de onda de 565 nm; los conos verdes a 535 nm; y los conos azules a 500 nm. Además, contamos con un cuarto tipo de fotorreceptor que no está implicado en la percepción del color pero sí en la visión en condiciones de baja luminosidad: los bastones, con una sensibilidad máxima a la luz de 500 nm.

Para formar la imagen de un determinado color, los observadores normales requieren una combinación de como mucho tres colores independientes, y así decimos que su visión del color es tricromática. Sin embargo, hay un amplio porcentaje de varones que tienen una deficiencia en la visión del color como consecuencia de la pérdida de los pigmentos de los conos verdes o los rojos; con lo que su visión pasaría a ser dicromática. Y además, existe la acromatopsia que es la ausencia de discriminación del color y una afección rara (1:100000). Las personas acromáticas pueden distinguir diferencias en los colores por ajuste de sus intensidades relativas usando los bastones; su visión es entonces monocromática.

La acromatopsia puede provenir de los fotorreceptores (es decir, los conos) o del sistema nervioso central. Se ha visto que la acromatopsia adquirida puede venir tras el daño cortical. En el caso de que la acromatopsia se deba a un problema con los fotorreceptores, podría ser la ausencia o disfunción de todos los tipos de conos, o de dos de los tres conos. Si solo se dispone de un único tipo de cono, este intervendrá en las correspondencias de color a alta luminosidad, y el sistema de bastones (como ocurre en personas normales) participará en condiciones de baja luminosidad. En caso de no tener ningún tipo de cono, todas las correspondencias de color recaerán en los bastones.

En el artículo científico de Nathans et al., 1989 (1) distinguen tres categorías de acromatopsia:

  1. Monocromatomatismo de bastones (típico): con niveles normales de rodopsina y función normal de los bastones pero con falta de toda sensibilidad mediada por pigmentos de los conos.
  2. Monocromatomatismo de bastones (atípico): solo se tiene visión por los bastones. Aún así, sus conos contienen cantidades normales de los pigmentos necesarios para ver.

 

Señalar que en la página de Orphanet, solo se habla de acromatopsia o monocromatismo de bastones, a secas.

  1. Monocromatismo de conos azules: tienen bastones y conos azules.

Clínicamente, los individuos de las tres categorías comparten una serie de síntomas, especialmente a edades jóvenes. Por ejemplo: todas las personas con monocromatismo no discriminan los colores o lo hacen pobremente; padecen nistagmo que disminuye con la edad, y fotofobia.

El monocromatismo de conos azules se distingue de los otros dos tipos gracias a los estudios de electrorretinografía a diferentes longitudes de onda. En este test se mide los mecanismos activos de los conos (si es que hay alguno).

A modo ilustrativo, en los pacientes examinados en Ayaggari et al., 2000 (2), las respuestas fotópicas generalmente estaban reducidas a niveles cercanos al ruido, indicando una ausencia retinal amplia de conos rojos y verdes que son los que normalmente dominan la respuesta adaptada a la luz. Sin embargo, tres de las diez familias del estudio tenían individuos con una preservación relativa anómala de la onda fotópica b. El valor más bajo dentro de la normalidad en nuestro sistema es aproximadamente de 55 μV, y tal como se muestra en la figura a continuación, los individuos KB y SB presentan una respuesta fotópica de 25–30 μV.

Figura de Ayaggari et al., 2000 (2)
Figura de Ayaggari et al., 2000 (2)

 

Para el diagnóstico, además de los estudios de electrorretinografía, se cuenta con la historia familiar porque es una enfermedad hereditaria ligada al cromosoma X, mientras que los otros dos monocromatismos son autosómicos recesivos.  Los genes que codifican los pigmentos fotosensibles rojos y verdes están presentes en el cromosoma X, mientras que los que lo hacen para el azul están en el cromosoma 7.

Así, como hemos visto el monocromatismo de conos azules se caracteriza por alteraciones en los conos tanto verdes como rojos, cuyos genes están situados en regiones muy cercanas, lo que sugiere que los genes de ambos son altamente homólogos y probablemente vienen de un gen ancestral común siguiendo una duplicación reciente. El genotipo reportado en pacientes de monocromatismo de conos azules incluye deleciones en la región de control del locus, pérdida parcial o completa de los genes de los pigmentos verdes y/o rojos y deleciones en combinación con mutaciones puntuales en los genes de los pigmentos rojos y verdes.

En cuatro de las doce familias del estudio de Nathans et al., 1989 (1), el fenotipo del monocromatismo de conos azules estaba causado por una mutación en un punto superpuesto no detectable por blot de ADN. Para comprobar dicha hipótesis, se aislaron clones genómicos conteniendo los genes del rojo o bien, híbridos rojo-verde se aislaron del ADN de varones afectados en cada una de las cuatro familias. La secuenciación de nucleótidos mostró solamente un cambio de timina a citosina en el exón 4 del nucléotido 1101. Esto provocaba un cambio del aminoácido cisteína a arginina en un aminoácido; cuando la cisteína es necesaria para estabilizar la proteína de los receptores.

Figura de Nathans et al., 1989 (1)
Figura de Nathans et al., 1989 (1)

¿Por qué es muy interesante estudiar el monocromatismo de conos azules? Porque como brillantemente explica el doctor Litos (en esta charla, por ejemplo) sirve para conocernos mejor a nosotros mismos y eso es impagable. Y además, como ya señalaban en 1989 Nathans et al., estas alteraciones visuales hereditarias no afectan a la longevidad ni a la fecundidad, por lo que se prevé que aumente la población afectada.

Y ahora todos somos un poquito más sabios gracias a Renata Sarno, y a la sección de noticias de Nature.

Para saber más

Sobre cómo funciona la visión humana, un artículo de Óscar Huertas Rosales

Más técnico en:

(1)   Nathans, J., Davenport, C., Maumenee, I., Lewis, R., Hejtmancik, J., Litt, M., Lovrien, E., Weleber, R., Bachynski, B., Zwas, F., & et, A. (1989). Molecular genetics of human blue cone monochromacy Science, 245 (4920), 831-838 DOI: 10.1126/science.2788922

(2)   Ayyagari, R., Kakuk, L., Bingham, E., Szczesny, J., Kemp, J., Toda, Y., Felius, J., & Sieving, P. (2000). Spectrum of color gene deletions and phenotype in patients with blue cone monochromacy Human Genetics, 107 (1), 75-82 DOI: 10.1007/s004390000338

Este artículo ha sido escrito por Dolores Bueno López como colaboración con Raras pero no invisibles. Podéis seguirla en @ununcuadio

697 pensamientos sobre “Renata Sarno y el monocromatismo de conos azules”

  1. Me gustaría tener información tanto de investigaciones como cualquier novedad acerca de esta enfermedad, tengo dos hijos de 4 y 8 meses que padecen esta enfermedad.

    Muchas gracias

    1. si usted tiene niños con el monocromatismo de conos azules, llegado a nuestro foro bcmfamilies.ning.com y te puedo enviar información sobre las nuevas investigaciones sobre la terapia génica y las pruebas de ADN
      Renata

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