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Michael Rudolf Robert Boehm, Christina Nolte, Arnd Heiligenhaus, Solon Thanos; The retina and the ascending visual pathway share common age-related protein changes. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3464.
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The visual consequences of age-related alterations in the neural retina are well documented, but little is known about the alterations along the visual pathway. We previously discovered distinct proteins, e.g. PARK [Parkinson disease (autosomal recessive, early onset)] 7/DJ-1 (DJ-1), stathmin (STMN), peroxiredoxin (Prx), and beta-synuclein (SNCB) that are regulated in the aging retina. Here, we performed a comparative analysis of these proteins along the post-laminar visual pathway in rats, in order to unravel common age-related changes.
Expression of DJ-1, STMN, Prx and SNCB were compared in the newborn, juvenile, middle-aged, and aged parts of the visual pathway including optic tract (OT), thalamus (TH), superior colliculus (SC) and visual cortex (VC). The frontal cortex (FC) served as non-visually associated area. Western-blot (WB), quantitative reverse-transcriptase PCR (qRT-PCR), and immunohistochemistry (IHC) analyses were employed to determine whether changes identified by proteomics were verifiable at the cellular and molecular level. Then we selected one of these proteins (SNCB) to study its function in cultured neurons obtained from either the postnatal retina or the cortex.
Changes of the proteins were found throughout the life of rats. The alterations were analogous to the retinal profiles. WB, IHC and qRT-PCR analyses confirmed these findings. The proteins were localized in certain cerebral areas within the visual pathway and the frontal cortex, therefore assigning them a role within the maturating visual pathway and brain. In-vitro studies with SNCB showed changes in the pattern of cell differentiation and growth, thus indicating its involvement in differentiation of cerebral and retinal ganglion cells.
This study is the first to provide evidence that DJ-1, STMN, Prx and SNCB are associated with aging within the visual pathway. These changes occur in key functional pathways during the processing of visual signals and may be involved in the development of age-related pathologies. SNCB is strongly involved in key pathways of cerebral and retinal ganglion cells. Most likely, SNCB and perhaps the other proteins influence key pathways triggering differentiation of visually relevant neuronal cells. Supported by the DFG-Excellence Cluster “Cells in Motion, CiM”, area C.4 and the DFG-grant Th386 20-1
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