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Effects of Optic Nerve Section in the Retina

Tipo: Artículo
Autores: Germain, F.; Blanco, R.; de la Villa, Pedro.
Títuto Revista: Optic Nerve Disease Research Perspectives
Centro: 09 - UAH

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Effects of Optic Nerve Section in the Retina
Authors:  Francisco Germain, Román Blanco and Pedro de la Villa
The retina is a privileged tissue to study the Central Nervous System due to the
disposition in layers of different types of cells and synaptic plexus. By cutting the axon
not only the nervous transmission is interrupted, but also an apoptotic death is induced in
axotomized neurons. The study of morphological and functional changes of surviving
retinal ganglion cells (RGCs) after axotomy is important in order to be able to predict cell
survival, structure restoration and functional recovery. After axotomy there was a
progressive decrease in RGCs count with a death peak in the second week. In relation
with this cellular decrease in the ganglion cell layer, a significant reduction in the
thickness of the inner plexiform and ganglion cell layers of retinal cross-sections was
observed. Immunohistochemical studies also showed a remarkable disorganisation of the
layer stratification in the inner plexiform layer. However, some RGCs survive longer and
develop changes such as growth cones and abnormal processes, probably trying to adapt
to a new situation. Also an increase in the diameter of the soma and dendritic field was
observed. The morphometrical analysis of the surviving axotomized RGCs showed that
the number of dendritic segments did not differ significantly of control animals, however,
their length was longer in axotomized cells than in control cells. These few surviving
cells experienced significant morphological changes that were studied by light
microscopy after neurobiotin injection, transmission and scanning electron microscopy.
Ultrastructural analyses showed cytoplasmic vacuolar degeneration and signs of
membrane alteration suggesting that axotomy causes severe alterations in the
cytoskeleton. The functionality and possible connections with other cells are unknown.
To study functional changes of rabbit RGCs receptors in surviving cells two weeks after
axotomy, dissociated RGCs were recorded by whole cell patch-clamp technique. The
ionic currents induced by the application of excitatory (AMPA / kainate) and inhibitory
(GABA) neurotransmitter agonist in injured RGCs were analyzed and compared with cells from control retinas. While excitatory neurotransmitters were unable of inducing
ionic currents, the amplitudes of the GABA-induced currents were decreased to 20 % of
control. After optic nerve section, large RGCs have shown greater survival than other
types, possibly it might be in relation with these structural and functional adaptive
changes in neurotransmitter receptor. Knowledge of the action mechanisms, as well as
the determination of no return point in the evolution of the lesion are aspects that must be
known before to start a therapy.