Publication: Immediate upregulation of proteins belonging to different branches of the apoptotic cascade in the retina after optic nerve transection and optic nerve crush.
Authors
Agudo, Marta ; Pérez Marín, María C. ; Sobrado Calvo, Paloma ; Lönngren, Ulrika ; Cánovas, Isabel ; Miralles Imperial, Jaime ; Hallböök, Finn ; Vidal Sanz, Manuel ; Salinas Navarro, Manuel Ángel ; Nadal-Nicolás, Francisco Manuel
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Publisher
Association for Research in Vision and Ophthalmology
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DOI
https://doi.org/10.1167/iovs.08-2404
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info:eu-repo/semantics/article
Description
© 2009 The Association for Research in Vision and Ophthalmology, Inc. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Published Manuscript version of a Published Work that appeared in final form in Investigative Ophthalmology & Visual Science. To access the final edited and published work see https://doi.org/10.1167/iovs.08-2404
Abstract
Purpose. To further investigate the molecular signals underlying optic nerve (ON) injury, the authors analyzed in adult control, ON-transected, and ON-crushed retinas the expression pattern and time-course regulation of the following proteins, all of which are linked to apoptosis through different pathways: Stat 1, caspase 11 (inflammation and death), cathepsins C and B (lysosomal death pathway), calpain 1 (endoplasmic reticulum stress), calreticulin (apoptosis marker), Jun (early response), and aryl hydrocarbon receptor (cell cycle arrest).
methods. Adult female rats were subjected to intraorbital optic nerve transection (IONT) or intraorbital optic nerve crush (IONC). Protein from naive and ON-injured adult rat retinas was extracted at different times postlesion, and Western blotting experiments were performed. For immunohistofluorescence analyses, retinal ganglion cells (RGCs) were retrogradely identified with fluorogold applied to the superior colliculi 1 week before injury.
results. Western blotting analyses revealed upregulation of all the analyzed proteins as early as 12 hours postlesion (hpl), peaking at 48 hpl, in agreement with our previous RNA study findings. Furthermore, immunohistofluorescence to radial sections showed that all but Stat 1 were expressed by the primarily injured neurons, the RGCs, as seen by colocalization with fluorogold.
conclusions. All analyzed proteins were upregulated in the retina after IONT or IONC as early as 12 hpl, indicating that ON injury regulates several branches of the apoptotic cascade and suggesting that commitment to death might be an earlier event than previously anticipated.
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Citation
Investigative Ophthalmology & Visual Science, 2009, Vol.50, Issue 1, pp.424-431
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Este ítem está sujeto a una licencia Creative Commons. http://creativecommons.org/licenses/by-nc-nd/4.0/