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S. E. MacNamee, S. D. Crish, S. Juliao, W. S. Lambert, D. J. Calkins; BDNF and TrkB Expression in the Retina of the DBA/2J Mouse Model of Glaucoma. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2123.
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© ARVO (1962-2015); The Authors (2016-present)
Evidence suggests that in glaucoma elevated ocular pressure obstructs retrograde BDNF transport, causing neurotrophin deprivation and RGC apoptosis. However, application of BDNF has been of limited neuroprotective success indicating that BDNF processing, while clearly important, may be more complicated. BDNF’s action is primarily through its high affinity receptor, TrkB, which is expressed in both full length and truncated variants. Truncated TrkB receptors have been regarded as passive ‘BDNF scavengers’ or inhibitors of TrkB full-length signaling. We examined relative expression and localization of BDNF as well as the localization of its precursor proBDNF and TrkB in the retina of the DBA/2J mouse model of hereditary glaucoma.
Quantitative RT-PCR was used to measure BDNF expression in freshly dissected retinas. For immunochemistry, retinas were dissected from aldehyde-perfused DBA/2J and C57 mice between 3 and 12 months of age. Immuno-staining was performed on whole retinas and vertical cross-sections using commercial antibodies against BDNF, proBDNF, TrkB, and a truncated TrkB receptor variant.
BDNF expression increased in the DBA/2J retina relative to the C57 at all ages. As DBA/2J age increased from 3 to 9 months, BDNF transcription increased approximately 2-fold. However, as IOP increased BDNF transcription at a given age decreased. BDNF was most heavily concentrated in astrocytes of the nerve fiber layer in the C57 and DBA/2J at all ages. Surprisingly, proBDNF was not found in astrocytes but localized exclusively to ganglion cell bodies. As DBA/2J age and IOP increased, BDNF was observed in Mueller glia as well. TrkB is expressed as a kinase-active receptor in ganglion cells, but in astrocytes it is primarily expressed in its truncated form.
Retinal ganglion cells in the DBA/2J continue to synthesize BDNF during disease progression, as indicated by robust proBDNF. Despite a high degree of mature BDNF in astrocytes, they lacked proBDNF suggesting acquisition from an outside source. It is likely astrocytic BDNF is internalized via the truncated TrkB receptor, thus competing with TrkB full-length signaling in ganglion cells.
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