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P. Balaram, S. D. Crish, D. J. Calkins; Upregulation of Brain Derived Neurotrophic Factor is Related to Transport Loss in the Superior Colliculus of the DBA/2J Mouse. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4061.
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In glaucoma, loss of neurotrophic support to retinal ganglion cells (RGCs) is thought to contribute to cell death in the retina. Elevated intraocular pressure is believed to induce blockade of retrograde transport of brain derived neurotrophic factor (BDNF) at the optic nerve head. Here we ask whether loss of axonal transport modulates expression of BDNF at the source of uptake in the DBA/2J mouse model of hereditary glaucoma, by comparing BDNF localization with axonal transport in the superior colliculus and optic nerve.
We administered intravitreal injections of the neuronal tracer cholera toxin β subunit (CTB) conjugated to an AlexaFluor fluorophore to age-matched DBA/2J and C57/BL6 mice. The animals were perfused forty-eight hours later, and 50 µm cross-sections of SC and 10µm longitudinal sections of ON were taken. These sections were photographed for CTB fluorescence in the colliculus and then stained for BDNF using immunofluorescent labeling. CTB tracing across the colliculus was reconstructed digitally to produce a three-dimensional distribution map and compared to the distribution of BDNF. BDNF staining was also compared to CTB labeling in the optic nerve.
Regions of the DBA/2J colliculi with a full complement of CTB transport had an even distribution of BDNF across layer III and a sparse distribution in layer II. In contrast, in regions of the DBA/2J colliculus that demonstrated deficient transport of CTB we found an elevation of BDNF localization in layer II. In the optic nerves of both DBA/2J and control mice, BDNF staining was strong and consistent throughout the entire ON regardless of representation in the colliculus, but abruptly terminated about 0.3 mm from the optic nerve head.
Upregulation of BDNF at the site of transport deficiency in the colliculus of the DBA/2J may be in response to loss of retinal input to these regions. In the optic nerve, loss of BDNF immunoreactivity at the nerve head seems to be a normal condition for both control and experimental animals. We suggest that the abrupt loss of BDNF is due to a change in transport mechanism, such as a shift from axonal transport to vesicular transport. IOP-induced blockade as reported in other studies may be due to a specific functional deficit in this transition.
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