REVISTA

La activación de la chaperona molecular, receptor sigma 1, preserva la función del cono en un modelo murino de degeneración retiniana hereditaria

Descripción: En un modelo animal de degeneración retiniana hereditaria grave, el fármaco pentazocina permite la supervivencia de las células cónicas

TITULO FUENTE ORIGINAL:

La activación de la chaperona molecular, receptor sigma 1, preserva la función del cono en un modelo murino de degeneración retiniana hereditaria

AUTORES:

Wang J, Saul A, Roon P, Smith SB

REVISTA ABREV.:

Proc Natl Acad Sci US A

AÑO:

2016

REFERENCIA:

113 (26): E3764-72

DOI:

10.1073 / pnas.1521749113

RESUMEN ORIGINAL:

Retinal degenerative diseases are major causes of untreatable blindness, and novel approaches to treatment are being sought actively. Here we explored the activation of a unique protein, sigma 1 receptor (Sig1R), in the treatment of PRC loss because of its multifaceted role in cellular survival. We used Pde6β(rd10) (rd10) mice, which harbor a mutation in the rod-specific phosphodiesterase... + Leer más

Retinal degenerative diseases are major causes of untreatable blindness, and novel approaches to treatment are being sought actively. Here we explored the activation of a unique protein, sigma 1 receptor (Sig1R), in the treatment of PRC loss because of its multifaceted role in cellular survival. We used Pde6β(rd10) (rd10) mice, which harbor a mutation in the rod-specific phosphodiesterase gene Pde6β and lose rod and cone photoreceptor cells (PRC) within the first 6 wk of life, as a model for severe retinal degeneration. Systemic administration of the high-affinity Sig1R ligand (+)-pentazocine [(+)-PTZ] to rd10 mice over several weeks led to the rescue of cone function as indicated by electroretinographic recordings using natural noise stimuli and preservation of cone cells upon spectral domain optical coherence tomography and retinal histological examination. The protective effect appears to result from the activation of Sig1R, because rd10/Sig1R(-/-) mice administered (+)-PTZ exhibited no cone preservation. (+)-PTZ treatment was associated with several beneficial cellular phenomena including attenuated reactive gliosis, reduced microglial activation, and decreased oxidative stress in mutant retinas. To our knowledge, this is the first report that activation of Sig1R attenuates inherited PRC loss. The findings may have far-reaching therapeutic implications for retinal neurodegenerative diseases

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Enlace al pdf de acceso libre: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC[...]