Early remodeling in an inducible animal model of retinal degeneration.
Neuroscience
; 160(2): 517-29, 2009 May 05.
Article
en En
| MEDLINE
| ID: mdl-19272416
ABSTRACT
Photoreceptor degeneration is followed by significant morphological changes in the second-order retinal neurons in humans and in several genetic animal models. However, it is not clear whether similar changes occur when photoreceptor degeneration is induced nongenetically, raising the question whether these changes are a general effect of deafferentation independent of the cause of degeneration. We addressed this by inducing selective photoreceptor degeneration with N-methyl-N-nitrosourea (MNU) and studying its effects on inner retinal neurons in a mouse for up to 3 months, using immunocytochemistry and iontophoretic labeling. To develop objective measures of photoreceptor degeneration and of retinal remodeling, we measured several retinal proteins using immunoblot analysis, and quantified gross visual ability of the animal in a visual cliff test. The MNU-induced progressive degeneration of rods and cones was associated with declining levels of postsynaptic density 95 protein in the retina, and with deteriorating visual performance of the animal. Müller glial cells showed enhanced reactivity for glial fibrillary acidic protein as demonstrated by immunocytochemistry, which also reflected in increased levels of the protein as demonstrated by immunoblotting. Horizontal cells and rod bipolar cells progressively lost their dendritic processes, which correlated with a slight decline in the levels of calbindin and protein kinase C alpha respectively. Horizontal cell axons, immunoreactive for nonphosphorylated neurofilaments, showed sprouting into the inner nuclear layer. Ganglion cells and their synaptic inputs, probed by immunolocalizing beta-III-tubulin, neurofilaments, bassoon and synaptophysin, appeared to be unaffected. These results demonstrate that MNU-induced photoreceptor degeneration leads to retinal remodeling similar to that observed in genetic models, suggesting that the remodeling does not depend on the etiopathology that underlies photoreceptor degeneration.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Degeneración Retiniana
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Células Fotorreceptoras de Vertebrados
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Alquilantes
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Metilnitrosourea
/
Degeneración Nerviosa
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Regeneración Nerviosa
Límite:
Animals
Idioma:
En
Revista:
Neuroscience
Año:
2009
Tipo del documento:
Article
País de afiliación:
India