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Yuyi You, Vivek Kumar Gupta, Alexander Klistorner, Stuart Graham; Molecular and histological changes in the dLGN and cortices and their time-course secondary to trans-synaptic degeneration after optic nerve injury. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1411.
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Anterograde trans-synaptic degeneration along the visual pathway has been observed in glaucomatous patients and experimental glaucoma models. The aim of this study is to investigate the mechanisms and extent of trans-synaptic changes in the visual system as well as in the distant somatosensory cortex using a rodent model of optic nerve axotomy. It is known that the rat primary somatosensory centre has structural and functional inter-linkages with the visual cortex.
Optic nerve injury in the form of axotomy was performed in adult Sprague-Dawley rats. Animals were sacrificed at regular time points and tissues harvested. Immunoblotting followed by densitometric analysis was used to determine the phosphorylation profile of Akt in the dorsal lateral geniculate nucleus (dLGN), the visual cortex and the primary somatosensory cortex (S1). The neuronal cell size and cell density were measured using Nissl staining. The prevalence of apoptosis was characterized by terminal deoxynucleotidyl-transferase-mediated biotin-dUTP nick end labelling (TUNEL) histochemistry.
An early and sustained loss of Akt phosphorylation was observed after optic nerve injury in both dLGN and visual cortex. At week one, a decrease in the neuronal cell size (p=0.042) and an increase of TUNEL positive cells (p<0.001) were evident in the dLGN but not in the visual cortex. A significant decline in neuronal cell number (p=0.048), cell size (p=0.001) and an increase in apoptotic cells (p<0.001) appeared in the visual cortex initially at one month post-transection. Immunohistochemistry showed that both neurons and glial cells were affected in trans-synaptic degeneration. There were no histological or apoptotic changes observed in S1, but an increase of Akt phosphorylation was found from month 1 after optic nerve axotomy.
Trans-synaptic degeneration along the visual pathway takes place in target relay (dLGN) and visual cortex following the optic nerve injury. Reduction of Akt phosphorylation preceded cellular and apoptotic changes. The up-regulation of Akt in S1 suggests that activation of the Akt signalling may be an early response to stress in trans-synaptic degeneration, which protects neurons from apoptosis.
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