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TIP. Revista especializada en ciencias químico-biológicas
versión impresa ISSN 1405-888X
TIP vol.8 no.2 Ciudad de México dic. 2005
Artículos de revisión
Relación de la estructura de los receptores NMDA con su función en la retina
Structure-function relationship of NMDA receptors in the retina
1Instituto de Fisiología Celular, UNAM. Apdo. Postal 70-253, C.P. 04510. México, D.F., México.
La función del glutamato en la retina, como neurotransmisor, factor trófico o neurotoxina, se relaciona directamente con la diversidad y la composición heteromérica de sus receptores. Los receptores de glutamato de tipo NMDA (NMDARs) son tetrámeros integrados por dos subunidades NR1, que forman un canal iónico permeable al calcio, y subunidades NR2 y NR3, que modulan su actividad.
Los NMDARs de la retina incluyen subunidades NR2, así como variantes postranscripcionales de NR1 específicas, tanto en el tejido diferenciado como el embrionario, cuya estructura determina diferencias funcionales significativas entre el cerebro y la retina. Consecuentemente, fármacos que protegen a las neuronas de la excitotoxicidad del glutamato en el cerebro, no tienen efecto en la retina.
La repercusiónclínica de estos resultados es evidente, ya que permitirá, en el futuro, el diseño de compuestos protectores de la muerte neuronal en la retina en padecimientos relacionados con la elevación de la concentración extracelular del glutamato, como el glaucoma, la oclusión vascular, la neuropatía óptica y la isquemia, entre otros.
Palabras Clave: Desarrollo embrionario; neurotransmisión; NR1; NR2; receptor de glutamato
The multiple actions of glutamate in the retina, as a neurotransmitter, a trophic factor or a neurotoxin, are directly related to the heteromeric composition of the NMDA type of glutamate receptors present in this tissue. The tetrameric NMDARs include two NR1 subunits which form the calcium-permeable cation channel, in addition to NR2 and NR3 subunits which modulate its activity.
Recent results demonstrate that retinal NMDARs might include tissue-specific NR1 splice variants and NR2 subunits, in both mature and embryonic tissue, which determine structural and functional differences with brain receptors. As a consequence, drugs shown to protect brain neurons from glutamate-induced neuronal death, are ineffective in the retina.
The clarification of the precise subunit composition of NMDARs in the retina will allow the future design of drugs aimed to prevent neuronal loss in pathological conditions such as glaucoma, vascular occlusion, optic neuropathy and ischemia, in which glutamate excitotoxicity seems to be involved.
Key Words: Embryonic development; neurotransmission; NR1; NR2; glutamate receptors
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Recibido: 06 de Octubre de 2005; Aprobado: 10 de Noviembre de 2005
Este es un artículo publicado en acceso abierto bajo una licencia Creative Commons
